Intrinsic graph structure estimation using graph Laplacian.
A graph is a mathematical representation of a set of variables where some pairs of the variables are connected by edges. Common examples of graphs are railroads, the Internet, and neural networks. It is both theoretically and practically important to estimate the intensity of direct connections between variables. In this study, a problem of estimating the intrinsic graph structure from observed data is considered. The observed data in this study are a matrix with elements representing dependency between nodes in the graph. The dependency represents more than direct connections because it includes influences of various paths. For example, each element of the observed matrix represents a co-occurrence of events at two nodes or a correlation of variables corresponding to two nodes. In this setting, spurious correlations make the estimation of direct connection difficult. To alleviate this difficulty, a digraph Laplacian is used for characterizing a graph. A generative model of this observed matrix is proposed, and a parameter estimation algorithm for the model is also introduced. The notable advantage of the proposed method is its ability to deal with directed graphs, while conventional graph structure estimation methods such as covariance selections are applicable only to undirected graphs. The algorithm is experimentally shown to be able to identify the intrinsic graph structure.


The Influence of Arginine on the Response of Enamel Matrix Derivative (EMD) Proteins to Thermal Stress: Towards Improving the Stability of EMD-Based Products.
In a current procedure for periodontal tissue regeneration, enamel matrix derivative (EMD), which is the active component, is mixed with a propylene glycol alginate (PGA) gel carrier and applied directly to the periodontal defect. Exposure of EMD to physiological conditions then causes it to precipitate. However, environmental changes during manufacture and storage may result in modifications to the conformation of the EMD proteins, and eventually premature phase separation of the gel and a loss in therapeutic effectiveness. The present work relates to efforts to improve the stability of EMD-based formulations such as Emdogain™ through the incorporation of arginine, a well-known protein stabilizer, but one that to our knowledge has not so far been considered for this purpose. Representative EMD-buffer solutions with and without arginine were analyzed by 3D-dynamic light scattering, UV-Vis spectroscopy, transmission electron microscopy and Fourier transform infrared spectroscopy at different acidic pH and temperatures, T, in order to simulate the effect of pH variations and thermal stress during manufacture and storage. The results provided evidence that arginine may indeed stabilize EMD against irreversible aggregation with respect to variations in pH and T under these conditions. Moreover, stopped-flow transmittance measurements indicated arginine addition not to suppress precipitation of EMD from either the buffers or the PGA gel carrier when the pH was raised to 7, a fundamental requirement for dental applications.


Organization of cortical activities related to movement in humans.
The extent and function of synchronization of oscillatory elements in the human sensorimotor cortex during movement remains unclear. Here we determine whether synchronization is distributed in both the spatial and frequency domains and whether it changes according to task. Electrocorticographic (ECoG) signals were recorded from presumed nonpathological areas simultaneously with electromyographic (EMG) signals from upper limb muscles during isometric and phasic movement tasks in humans with subdural electrodes in situ for investigation of epilepsy. Functional mapping of the sensorimotor cortex was performed by previous electrical stimulation through the same ECoG electrodes used for recording. Significant coherence between ECoG and EMG was seen at discrete frequencies in the range of 7-100 Hz. There was no predilection for coherence within a given frequency band to be associated with cortical sites that had been functionally defined as producing contralateral arm motor responses on stimulation. However, coherence with muscle in the 7-14 and 15-30 Hz band tended to be associated with ECoG sites that lay close to or within the central sulcus as determined intraoperatively. The spatial pattern and frequency of coherence changed with different tasks, although similarities in the coherence pattern remained for tasks that shared common features. These findings provide support for the hypothesis that that synchronization at specific frequencies links cortical activities into a functional ensemble during voluntary movement.


Real-Time Artifacts Reduction during TMS-EEG Co-Registration: A Comprehensive Review on Technologies and Procedures.
Transcranial magnetic stimulation (TMS) excites neurons in the cortex, and neural activity can be simultaneously recorded using electroencephalography (EEG). However, TMS-evoked EEG potentials (TEPs) do not only reflect transcranial neural stimulation as they can be contaminated by artifacts. Over the last two decades, significant developments in EEG amplifiers, TMS-compatible technology, customized hardware and open source software have enabled researchers to develop approaches which can substantially reduce TMS-induced artifacts. In TMS-EEG experiments, various physiological and external occurrences have been identified and attempts have been made to minimize or remove them using online techniques. Despite these advances, technological issues and methodological constraints prevent straightforward recordings of early TEPs components. To the best of our knowledge, there is no review on both TMS-EEG artifacts and EEG technologies in the literature to-date. Our survey aims to provide an overview of research studies in this field over the last 40 years. We review TMS-EEG artifacts, their sources and their waveforms and present the state-of-the-art in EEG technologies and front-end characteristics. We also propose a synchronization toolbox for TMS-EEG laboratories. We then review subject preparation frameworks and online artifacts reduction maneuvers for improving data acquisition and conclude by outlining open challenges and future research directions in the field.


NCOA4-RET and TRIM27-RET Are Characteristic Gene Fusions in Salivary Intraductal Carcinoma, Including Invasive and Metastatic Tumors: Is "Intraductal" Correct?
Intraductal carcinoma (IC) is the new WHO designation for tumors previously encompassed by "low-grade cribriform cystadenocarcinoma" and "low-grade salivary duct carcinoma." The relationship of IC to salivary duct carcinoma (SDC) is controversial, even though they are considered to be distinct entities. IC is a rare low-grade malignant salivary gland neoplasm with histopathological features reminiscent of atypical ductal hyperplasia or ductal carcinoma in situ of the breast, showing diffuse S100 protein and mammaglobin positivity, while it is partially defined genetically. Recently, RET rearrangements including NCOA4-RET and TRIM27-RET have been described in IC. Here, we genetically characterize the largest cohort of IC to date (33 cases) including 8 cases with focal or widespread invasive growth and 1 case with lymph node metastasis. Thirty-three cases of IC were analyzed by next-generation sequencing (NGS) using the FusionPlex Solid Tumor kit (ArcherDX). Identified gene fusions were confirmed using fluorescence in situ hybridization break-apart and fusion probes and an reverse transcription polymerase chain reaction designed specifically for the detected breakpoints. Ten cases of SDC were analyzed for comparison using NGS panels that detect mutations and fusion transcripts. NGS analysis detected an NCOA4-RET fusion transcript in 11 cases of intercalated duct-type IC joining exon 7 or 8 of NCOA4 gene and exon 12 of the RET gene. Eight cases of IC had an invasive growth pattern, including one with widespread invasion and lymph node metastasis. Three invasive ICs harbored an NCOA4-RET fusion transcript, while 1 case was negative, and 2 cases were not analyzable. In addition, a novel TRIM27-RET fusion transcript between exon 3 of TRIM27 and exon 12 of RET was identified in 2 cases of IC with apocrine features, and one of them displayed invasive growth. Two IC cases with invasive growth harbored novel fusions TUT1-ETV5 and KIAA1217-RET, respectively. A total of 42.4% of the cases in this series of IC harbored fusions involving RET. Such fusion transcripts were not detected in any of the 10 SDC cases. We have confirmed NCOA4-RET as a predominant fusion in intercalated duct-type IC, including 3 cases with invasive growth pattern. A novel finding in our series was a case of widely invasive intercalated duct-type IC, with a single lymph node metastasis that revealed an NCOA4-RET fusion transcript. We also demonstrated that a subset of apocrine ICs harbored a TRIM27-RET gene fusion, including one case with invasive growth. In contrast, neither NCOA4-RET nor TRIM27-RET fusions were detected in any tested SDCs. Thus, the distinct molecular findings in IC and SDC support that the tumors are separate malignant salivary tumor entities. The presence of tumor-type-specific NCOA4-RET or TRIM27-RET translocations in a subset of widely invasive carcinomas with intercalated duct-like immunoprofiles suggests that a recharacterization of IC including its redesignation as "intercalated duct carcinoma, invasive or noninvasive" may be appropriate.


Multipartnered fertility among American men.
Using the 2002 (Cycle 6) National Survey of Family Growth (NSFG), which was the first NSFG to interview men, we document the prevalence and correlates of sequential parenthood with different partners (multipartnered fertility) among a representative sample of American men. Nearly 8% of American men aged 15-44 report having had children with more than one partner, with sharp differences by age, race/ethnicity, and income-over one-third of poor black men aged 35-44 report having had children with two or more mothers, and 16% report children with three or more mothers. Fathers of two or more children by multiple partners appear to be more disadvantaged than fathers with two or more children by the same partner. Multipartnered fertility is strongly related to prior birth characteristics; men not in a coresidential union at the preceding birth are more likely to have their next birth with a new partner and controlling for prior-birth characteristics accounts for the elevated risk of Hispanics and blacks in baseline models. Results also suggest that multipartnered fertility is becoming more prevalent as younger cohorts transition to a new-partner birth more quickly and at a higher rate than older cohorts.


Magnetic Resonance Imaging as a Valuable Tool for Predicting Parametrial Invasion in Stage IB1 to IIA2 Cervical Cancer.
The aims of study were to determine the predictive value of preoperative magnetic resonance imaging (MRI) for parametrial invasion (PMI) and to develop a predictive model for PMI in patients with stage IB1 to IIA2 cervical cancer. We retrospectively analyzed patients with stage IB1 to IIA2 cervical cancer (n = 215) who underwent radical hysterectomy between 2003 and 2014. The presence of PMI from postoperative pathological reports and its association with preoperative MRI findings were evaluated. We developed a predictive model for PMI using independent predictive factors identified by logistic regression and estimated its predictive performance. Thirty patients (14.0%) had PMI from postoperative pathological reports. Among the preoperative MRI findings, a greater tumor diameter (4.2 vs 2.0 cm; P < 0.001), a larger tumor volume (92.6 vs 12.7 cm; P < 0.001), the presence of PMI (53.3% vs 8.6%; P < 0.001), and upper vaginal involvement (73.3% vs 22.7%; P < 0.001) were significantly associated with PMI. Multivariate analysis identified tumor volume (odds ratio, 7.0; 95% confidence interval, 2.63-18.53; P < 0.001) and PMI (odds ratio, 6.1; 95% confidence interval, 2.31-15.97; P < 0.001) from preoperative MRI findings as independent predictive factors for PMI. Our predictive model demonstrates that the presence of PMI or a tumor volume of greater than 18.0 cm has a higher sensitivity (86.7% vs 53.3%) and lower specificity (74.6% vs 91.4%) than the presence of PMI alone. Specifically, the model's negative predictive value was superior to that of PMI only (97.2% vs 92.3%). In the low-risk group, defined as preoperative MRI findings suggesting no PMI and a tumor volume of 18.0 cm or less, the proportion of false negative cases was just 2.8%. When tumor volume with findings suggesting that PMI is considered, preoperative MRI is useful in excluding PMI. A predictive model based on preoperative MRI findings seems to be valuable in identifying potential candidates for less radical surgery in stage IB1 to IIA2 cervical cancer.


International consensus statement on the peri-operative management of direct oral anticoagulants in cardiac surgery.
Despite current recommendations on the management of severe peri-operative bleeding, there is no pragmatic guidance for the peri-operative monitoring and management of cardiac surgical patients taking direct oral anticoagulants. Members of the Transfusion and Haemostasis Subcommittee of the European Association of Cardiothoracic Anaesthesiology, of their own volition, performed an independent systematic review of peer-reviewed original research, review articles and case reports and developed the following consensus statement. This has been endorsed by the European Association of Cardiothoracic Anaesthesiology. In our opinion, most patients on direct oral anticoagulant therapy presenting for elective cardiac surgery can be safely managed in the peri-operative period if the following conditions are fulfilled: direct oral anticoagulants have been discontinued two days before cardiac surgery, corresponding to five elimination half-live periods; in patients with renal or hepatic impairment or a high risk of bleeding, a pre-operative plasma level of direct oral anticoagulants has been determined and found to be below 30 ng.ml-1 (currently only valid for dabigatran, rivaroxaban and apixaban). In cases where plasma level monitoring is not possible (e.g. assay was not available), discontinuation for 10 elimination half-live periods (four days) is required. For FXa inhibitors, a standard heparin-calibrated anti-Xa level of < 0.1 IU.ml-1 should be measured, indicating sufficient reduction in the anticoagulant effect. Finally, short-term bridging with heparin is not required in the pre-operative period.


Disability, and not diabetes, is a strong predictor of mortality in oldest old patients hospitalized with pneumonia.
Pneumonia causes more deaths than any other infectious disease, especially in older patients with multiple chronic diseases. Recent studies identified a low functional status as prognostic factor for mortality in elderly patients with pneumonia while contrasting data are available about the role of diabetes. The aim of this study was to evaluate the in-hospital, 3-month and 1-year mortality in elderly subjects affected by pneumonia enrolled in the RePoSi register. We retrospectively analyzed the data collected on hospitalized elderly patients in the frame of the REPOSI project. We analyzed the socio-demographic, laboratory and clinical characteristics of subjects with pneumonia. Multivariate logistic analysis was used to explore the relationship between variables and mortality. Among 4714 patients 284 had pneumonia. 52.8% were males and the mean age was 80 years old. 19.8% of these patients had a Barthel Index ≤40 (p ˂ 0.0001), as well as 43.2% had a short blessed test ≥10 (p ˂ 0.0117). In these subjects a significant CIRS for the evaluation of severity and comorbidity indexes (p ˂ 0.0001) were present. Although a higher fasting glucose level was identified in people with pneumonia, in the multivariate logistic analysis diabetes was not independently associated with in-hospital, 3-month and 1-year mortality, whereas patients with lower Barthel Index had a higher mortality risk (odds ratio being 9.45, 6.84, 19.55 in hospital, at 3 and 12 months). Elderly hospitalized patients affected by pneumonia with a clinically significant disability had a higher mortality risk while diabetes does not represent an important determinant of short and long-term outcome.


Parameter Sensitivity of the Elastic Net Approach to the Traveling Salesman Problem.
Durbin and Willshaw's elastic net algorithm can find good solutions to the TSP. The purpose of this paper is to point out that for certain ranges of parameter values, the algorithm converges into local minima that do not correspond to valid tours. The key parameter is the ratio governing the relative strengths of the two competing terms in the elastic net energy function. Based on recent work by Durbin, Szeliski and Yuille, the parameter regime in which the net may visit some cities twice is examined. Further analysis predicts the regime in which the net may fail to visit some cities at all. Understanding these limitations allows one to select the parameter value most likely to avoid either type of problem. Simulation data support the theoretical work.


Discovering collectively informative descriptors from high-throughput experiments.
Improvements in high-throughput technology and its increasing use have led to the generation of many highly complex datasets that often address similar biological questions. Combining information from these studies can increase the reliability and generalizability of results and also yield new insights that guide future research. This paper describes a novel algorithm called BLANKET for symmetric analysis of two experiments that assess informativeness of descriptors. The experiments are required to be related only in that their descriptor sets intersect substantially and their definitions of case and control are consistent. From resulting lists of n descriptors ranked by informativeness, BLANKET determines shortlists of descriptors from each experiment, generally of different lengths p and q. For any pair of shortlists, four numbers are evident: the number of descriptors appearing in both shortlists, in exactly one shortlist, or in neither shortlist. From the associated contingency table, BLANKET computes Right Fisher Exact Test (RFET) values used as scores over a plane of possible pairs of shortlist lengths 12. BLANKET then chooses a pair or pairs with RFET score less than a threshold; the threshold depends upon n and shortlist length limits and represents a quality of intersection achieved by less than 5% of random lists. Researchers seek within a universe of descriptors some minimal subset that collectively and efficiently predicts experimental outcomes. Ideally, any smaller subset should be insufficient for reliable prediction and any larger subset should have little additional accuracy. As a method, BLANKET is easy to conceptualize and presents only moderate computational complexity. Many existing databases could be mined using BLANKET to suggest optimal sets of predictive descriptors.


Analysis of the Fenton-Karma model through an approximation by a one-dimensional map.
The Fenton-Karma model is a simplification of complex ionic models of cardiac membrane that reproduces quantitatively many of the characteristics of heart cells; its behavior is simple enough to be understood analytically. In this paper, a map is derived that approximates the response of the Fenton-Karma model to stimulation in zero spatial dimensions. This map contains some amount of memory, describing the action potential duration as a function of the previous diastolic interval and the previous action potential duration. Results obtained from iteration of the map and numerical simulations of the Fenton-Karma model are in good agreement. In particular, the iterated map admits different types of solutions corresponding to various dynamical behavior of the cardiac cell, such as 1:1 and 2:1 patterns. (c) 2002 American Institute of Physics.


Berberine inhibits the interleukin-1 beta-induced inflammatory response via MAPK downregulation in rat articular chondrocytes.
Osteoarthritis (OA) is one of the most chronic degenerative arthritic diseases, which gradually results in chondrocyte changes, articular cartilage degeneration, subchondral bone sclerosis, joint pain, swelling, and dysfunction. Berberine (BBR) has various confirmed biological activities, such as anti-inflammatory and antioxidant activities. However, the effect of BBR on the production of inflammation-associated proteins, including inducible nitric oxide synthase (iNOS), cyclooxygenase (Cox)-2, metalloproteinases (MMPs), Collagen II, TNF-α, and IL-6 via the MAPK (mitogen-activated protein kinases) pathway in IL-1β-stimulated rat chondrocytes, has not yet been studied. Thus, the purpose of this study was to evaluate whether BBR would decrease the production of inflammation-associated proteins through the MAPK signal pathway. Rat chondrocytes were cultured and pretreated with BBR at different concentrations (0, 25, 50, and 100 μM) and then stimulated with or without IL-1β (10 ng/mL). The mRNA expression of iNOS, COX-2, MMP-3, MMP-13, TNF-α, and IL-6 was measured by real-time polymerase chain reaction (RT-PCR), and the protein expression of iNOS, COX-2, Collagen II, MMP-3,MMP-13, and MAPKs were measured by Western blotting. The results showed that the expression of iNOS, COX-2, MMP-3, MMP-13, TNF-α, and IL-6 increased in the IL-1β-treated group and BBR showed an ability to inhibit the elevated expression under the pretreatment. Furthermore, the IL-1β-induced downregulation of Collagen II could be ameliorated by BBR. Moreover, the expression of MAPKs was significantly decreased by BBR. These results demonstrated that BBR had the anti-catabolic and anti-inflammation abilities that were through the MAPKs in IL-1β-induced rat chondrocytes. These findings may provide a novel therapeutic choice for treatment of OA using BBR.


Risk of nonfatal venous thromboembolism with oral contraceptives containing norgestimate or desogestrel compared with oral contraceptives containing levonorgestrel.
Previous studies have reported that users of the "third-generation" oral contraceptives (OCs) containing the progestins gestodene and desogestrel have about twice the risk for venous thromboembolism (VTE) compared to users of older OCs containing levonorgestrel. Estimates of the risk for VTE among users of norgestimate-containing OCs compared to other OCs, however, are lacking. The purpose of this study is to obtain quantitative information on the risk of nonfatal VTE in women using OCs containing either norgestimate or desogestrel in comparison with women taking OCs containing levonorgestrel. Based on information from PharMetrics, a United States-based company that collects and records information on claims paid by managed care plans, we used a nested case-control study design to estimate relative risks of nonfatal VTE among 15- to 39-year-old current users of OCs containing norgestimate with 35 microg of ethinyl estradiol (EE), desogestrel with 30 microg of EE or levonorgestrel with 30 microg of EE, both monophasic and triphasic preparations, during the period January 2000 to March 2005. Cases were women with a well-documented VTE of uncertain origin that was diagnosed in current users of a study drug. Up to four controls were closely matched to each case by age and calendar time, and odds ratios (ORs) were calculated using conditional logistic regression comparing the risk of VTE among users of the three contraceptives. We also estimated and compared the incidence rates for all three OCs. Based on 281 newly diagnosed idiopathic cases of VTE and 1055 controls, we found that the adjusted ORs for nonfatal VTE comparing norgestimate- or desogestrel-containing OC users to users of levonorgestrel-containing OCs were 1.1 [95% confidence interval (CI), 0.8-1.6] and 1.7 (95% CI, 1.1-2.4), respectively. The incidence rates of VTE were 30.6 (95% CI, 25.5-36.5), 53.5 (95% CI, 42.9-66.0) and 27.1 (95% CI, 21.1-34.3) per 100,000 woman-years for users of norgestimate-, desogestrel- and levonorgestrel-containing OCs, respectively. The incidence rate ratios for norgestimate-containing OCs compared to levonorgestrel-containing OCs and desogestrel-containing OCs compared to levonorgestrel-containing OCs were 1.1 (95% CI, 0.8-1.5) and 2.0 (95% CI, 1.4-2.7), respectively. The risk of nonfatal VTE among users of desogestrel-containing OCs is significantly elevated compared to that of levonorgestrel-containing OCs. The risk of VTE in users of norgestimate-containing OCs was closely similar to that of users of levonorgestrel-containing OCs.


Relationship between polycystic ovary syndrome and ancestry in European Americans.
To determine whether European Americans with polycystic ovary syndrome (PCOS) exhibit genetic differences associated with PCOS status and phenotypic features. Case-control association study in European Americans. Academic center. Women with PCOS diagnosed with the use of the National Institutes of Health criteria (n = 532) and control women with regular menstrual cycles and no evidence of hyperandrogenism (n = 432). Blood was drawn for measurement of sex steroids, metabolic parameters, and genotyping. Associations among PCOS status, phenotype, and genetic background identified with the use of principal component analysis. Principal component analysis identified five principal components (PCs). PC1 captured northwest-to-southeast European genetic variation and was associated with PCOS status. Acanthosis was associated with southern European ancestry, and larger waist:hip ratio was associated with northern European ancestry. PC2 was associated with east-to-west European genetic variation and cholesterol levels. These data provide evidence for genetic influence based on European ethnicity in women with PCOS. There is also evidence for a genetic component in the phenotypic features of PCOS within a mixed European population. The data point to the need to control for population stratification in genetic studies in women of mixed European ethnicity. They also emphasize the need for better studies of PCOS prevalence and phenotype as a function of genetic background.


PSA regulates androgen receptor expression in prostate cancer cells.
Prostate-specific antigen (PSA) is a pivotal downstream target gene of the androgen receptor (AR), and a serum biomarker to monitor prostate cancer (PrCa) progression. It has been reported that PSA transactivates AR, but the mechanistic requirements of this response have not been investigated. We studied the localization of PSA, AR, and Src in intracellular compartments of synthetic androgen (R1881)-stimulated LNCaP and C4-2B PrCa cells, using immunofluorescence and subcellular fractionation approaches. We also investigated the effect of downregulation of PSA on AR expression by immunoblotting and real-time PCR using short hairpin RNA (shRNA) and small interfering RNA (siRNA). Src activity was analyzed by immunoblotting. R1881 stimulation induced nuclear localization of both PSA and AR in LNCaP and C4-2B PrCa cells as well as increased phosphorylation of Src. Stable shRNA or transient siRNA knockdown of PSA resulted in reduced AR protein levels as well as AR mRNA levels in C4-2B cells. Similar to C4-2B cells, ablation of AR levels upon silencing of PSA was also confirmed in VCaP cells, another androgen-independent cell line. Silencing of PSA did not cause significant changes in Src activation; besides, Src regulation by integrins did not appear to affect AR transcriptional activity. PSA localizes to nuclei of androgen-stimulated PrCa cells, and controls AR mRNA and protein levels. This regulatory loop is specific for PSA, does not involve known AR activators such as Src and AKT, and may contribute to AR signaling under conditions of increasing PSA levels in patients.


miR393 and secondary siRNAs regulate expression of the TIR1/AFB2 auxin receptor clade and auxin-related development of Arabidopsis leaves.
The phytohormone auxin is a key regulator of plant growth and development that exerts its functions through F-box receptors. Arabidopsis (Arabidopsis thaliana) has four partially redundant of these receptors that comprise the TRANSPORT INHIBITOR RESPONSE1/AUXIN SIGNALING F-BOX1 auxin receptor (TAAR) clade. Recent studies have shown that the microRNA miR393 regulates the expression of different sets of TAAR genes following pathogen infection or nitrate treatment. Here we report that miR393 helps regulate auxin-related development of leaves. We found that AtMIR393B is the predominant source for miR393 in all aerial organs and that miR393 down-regulates all four TAAR genes by guiding the cleavage of their mRNAs. A mutant unable to produce miR393 shows developmental abnormalities of leaves and cotyledons reminiscent of enhanced auxin perception by TAARs. Interestingly, miR393 initiates the biogenesis of secondary siRNAs from the transcripts of at least two of the four TAAR genes. Our results indicate that these siRNAs, which we call siTAARs, help regulate the expression of TAAR genes as well as several unrelated genes by guiding the cleavage of their mRNAs. Thus, miR393 and possibly siTAARs regulate auxin perception and certain auxin-related aspects of leaf development.


No short-term respiratory effects among particle-exposed employees in the Stockholm subway.
Exposure to traffic-related air pollution is associated with adverse respiratory effects, but it is not known whether the high exposure to particles prevailing in the subway system may affect the respiratory system. We investigated airway inflammation and lung function among particle-exposed subway employees. We studied 81 workers. All participants were non-smokers, aged 25-50 years. Three exposure groups were formed according to particulate matter (PM) levels obtained during an occupational hygienic investigation: 30 platform workers [average PM(2.5) 63 µg/m(3) and DataRAM (MIE Inc, Billerica, Waltham, MA, USA) 182 µg/m(3)], 30 subway drivers (19 µg/m(3) and 33 µg/m(3)), and 21 ticket sellers (10 µg/m(3) and 13 µg/m(3)). We measured the fractional exhaled nitric oxide (FENO) of all workers before and after a workday. We also measured the peak expiratory flow (PEF) and forced expiratory volume in one second (FEV(1)) of platform workers and ticket sellers five times a day over two weeks. We calculated the arithmetic means of PEF and FEV(1) during exposed and unexposed time for every individual. There was no significant increase in FENO after work among platform workers, subway drivers or ticket sellers (the means of percentual individual change were -7%, +2% and -4% respectively). The averages of the ratios (exposed to unexposed time) of PEF and FEV(1) were above 1.0 for both ticket sellers (1.016 and 1.002 respectively) and platform workers (1.022 and 1.005). Our observations do not indicate any short-term respiratory effects of particle exposure in the subway among the employees, with respect to airway inflammation or lung function.


Postischemic inhibition of GABA reuptake by tiagabine slows neuronal death in the gerbil hippocampus.
The neuroprotective effects of enhancing neuronal inhibition with a gamma-aminobutyric acid (GABA) uptake inhibitor were studied in gerbil hippocampus following transient ischemia. We used in vivo microdialysis to determine a suitable dosing regimen for tiagabine (NNC328) to elevate extracellular levels of GABA within the hippocampus. In anesthetized (normothermic) gerbils, tiagabine (45 mg/kg, i.p.) selectively elevated extracellular GABA levels 450% in area CA1 of the hippocampus. In gerbils subjected to cerebral ischemia via 5-min bilateral carotid occlusion, extracellular GABA levels increased 13-fold in area CA 1 returning to baseline within 30-45 min. When tiagabine was injected 10 min following onset of reperfusion, GABA levels remained elevated (200-470%) for 90 min. In addition, tiagabine significantly reduced the ischemic-induced elevation of glutamate levels in area CA1 during the postischemic period when GABA levels were elevated. There was no effect of postischemic tiagabine on aspartate or six other amino acids. Using the same dosing regimen, we evaluated the degree of neuroprotection in the hippocampus of gerbils 4 and 21 days after ischemia. Tiagabine decreased body temperature a maximum of 2.7 degrees C beginning 30 min into reperfusion and lasting 90 min. In untreated gerbils sacrificed 4 and 21 days after ischemia, there was severe necrosis (99%) of the pyramidal cell layer in area CA1. Whereas tiagabine significantly protected the CA1 pyramidal cell layer in ischemic gerbils at 4 days (overt necrosis confined to about 17% of area CA1), the protection diminished significantly 21 days postischemia. When normothermia was maintained both during and after ischemia in a separate group of tiagabine-treated animals, approximately 77% of the CA1 pyramidal cell layer was necrotic at 4 days. Based on these findings, we suggest that 1) tiagabine slows the development of hippocampal degeneration following ischemia, and 2) that mild, postischemic hypothermia is responsible, in large part, for the neuroprotective actions of this drug. We conclude that the histological outcome after administration of cerebral neuroprotectants should be assessed following long-term survival.


Risk factors for hysterectomy among Mexican-American women in the US southwest.
The purpose of this study was to assess risk factors associated with a history of hysterectomy among Mexican-American women living in the United States Southwest. Mexican-American women ages 20-74 at time of interview were defined as a subpopulation among adults in the Hispanic Health and Nutrition Examination Survey (HHANES), 1982-1984. Language preference, reproductive history, level of education, poverty status, generation of immigration, marital status, and insurance coverage were examined in relation to risk of hysterectomy using weighted tabulation and logistic regression for data resulting from complex survey designs. Heretofore, language preference has not been a variable considered in relation to risk of hysterectomy. In the HHANES, over 60% of women who spoke English most often rather than Spanish reported a history of hysterectomy. Women who had previously been pregnant were almost four times as likely (odds ratio 3.972) to have had a hysterectomy compared to women who had never been pregnant. Women who expressed any preference for English were twice as likely (odds ratio 2.050) to have had a hysterectomy than were those who responded that they exclusively preferred Spanish. Age, higher levels of education, and higher economic status also increased the risk of hysterectomy. In contrast, reproductive history, marital status, prior tubal ligation, generation of immigration, and health insurance did not have substantial effects on the risk of hysterectomy. This study suggests that, in the future, the effect of language preference should not be overlooked when considering risk factors for hysterectomy.


Cognitive impairment and mortality in older community residents.
Cognitive impairment among the elderly has been linked to mortality in studies of clinical populations. The purpose of this study was to examine the mortality risk associated with cognitive impairment among elderly populations in the community. Cognitive impairment and other social and health factors were assessed in 1855 elderly community residents. This sample was reinterviewed periodically to assess changes in health and survival. At baseline 33% of the sample were mildly impaired and 8% were severely impaired. Across a 48-month observation period the survival probability was .85 for the cognitively unimpaired, .69 for the mildly impaired, and .51 for severely impaired respondents. When adjustments were made for the effects of other health and social covariates, severely impaired persons were twice as likely to die as unimpaired persons. Those who were mildly impaired were also at an increased risk. Other investigators have found that cognitive impairment is a significant predictor of dementia. We found that it is a significant predictor of mortality as well. Early detection of impaired cognition and attention to associated health problems could improve the quality of life of these older adults and perhaps extend their survival.


Community structure affects trophic ontogeny in a predatory fish.
While most studies have focused on the timing and nature of ontogenetic niche shifts, information is scarce about the effects of community structure on trophic ontogeny of top predators. We investigated how community structure affects ontogenetic niche shifts (i.e., relationships between body length, trophic position, and individual dietary specialization) of a predatory fish, brown trout (Salmo trutta). We used stable isotope and stomach content analyses to test how functional characteristics of lake fish community compositions (competition and prey availability) modulate niche shifts in terms of (i) piscivorous behavior, (ii) trophic position, and (iii) individual dietary specialization. Northern Scandinavian freshwater fish communities were used as a study system, including nine subarctic lakes with contrasting fish community configurations: (i) trout-only systems, (ii) two-species systems (brown trout and Arctic charr [Salvelinus alpinus] coexisting), and (iii) three-species systems (brown trout, Arctic charr, and three-spined sticklebacks [Gasterosteus aculeatus] coexisting). We expected that the presence of profitable small prey (stickleback) and mixed competitor-prey fish species (charr) supports early piscivory and high individual dietary specialization among trout in multispecies communities, whereas minor ontogenetic shifts were expected in trout-only systems. From logistic regression models, the presence of a suitable prey fish species (stickleback) emerged as the principal variable determining the size at ontogenetic niche shifts. Generalized additive mixed models indicated that fish community structure shaped ontogenetic niche shifts in trout, with the strongest positive relationships between body length, trophic position, and individual dietary specialization being observed in three-species communities. Our findings revealed that the presence of a small-sized prey fish species (stickleback) rather than a mixed competitor-prey fish species (charr) was an important factor affecting the ontogenetic niche-shift processes of trout. The study demonstrates that community structure may modulate the ontogenetic diet trajectories of and individual niche specialization within a top predator.


Perceptions of Teaching Methods for Preclinical Oral Surgery: A Comparison with Learning Styles.
Dental extraction is a routine part of clinical dental practice. For this reason, understanding the way how students' extraction knowledge and skills development are important. To date, there is no accredited statement about the most effective method for the teaching of exodontia to dental students. Students have different abilities and preferences regarding how they learn and process information. This is defined as learning style. In this study, the effectiveness of active learning in the teaching of preclinical oral surgery was examined. The personality type of the groups involved in this study was determined, and the possible effect of personality type on learning style was investigated. This study was undertaken over five years from 2011 to 2015. The sample consisted of 115 students and eight staff members. Questionnaires were submitted by 68 students and all eight staff members involved. Three measures were used in the study: The Index of Learning Styles (Felder and Soloman, 1991), the Myers-Briggs Type Indicator (MBTI), and the styles of learning typology (Grasha and Hruska-Riechmann). Findings indicated that demonstration and minimal clinical exposure give students personal validation. Frequent feedback on their work is strongly indicated to build the cognitive, psychomotor, and interpersonal skills needed from preclinical oral surgery courses. Small group cooperative active learning in the form of demonstration and minimal clinical exposure that gives frequent feedback and students' personal validation on their work is strongly indicated to build the skills needed for preclinical oral surgery courses.


Expansion of myelin autoreactive CD8+ T lymphocytes in patients with neuropsychiatric systemic lupus erythematosus.
Delineation of mechanisms underlying neuropsychiatric systemic lupus erythematosus (NPSLE) and determination of biological markers could guide treatment choice. A study was undertaken to analyse the potential role of activated CD8+ T cells in NPSLE as previously reported in SLE nephritis. Flow cytometric immunophenotyping of blood lymphocytes was performed in 30 patients with NPSLE and 36 healthy individuals. The antigenic specificity of CD8+ T cells was studied using HLA-A0201 tetramers loaded with several myelin-derived peptides. The intracellular level of interferon γ (IFNγ) produced by activated CD8+ T cells was determined by flow cytometry. A large increase in circulating activated CD8+ T lymphocytes expressing surface HLA-DR was found in patients with NPSLE without antiphospholipid syndrome (APS) (n=18) compared with patients with APS (n=12) or healthy controls (n=36). IFNγ-secreting myelin-specific CD8+ T cells were detected exclusively in the blood of patients with NPSLE without APS but with white matter lesions. These data strongly support the existence of a new immune effector mechanism responsible for CNS involvement in patients with NPSLE and suggest that analysing HLA-DR expression combined with myelin-specific tetramer staining on CD8+ T lymphocytes may be a valuable additional tool for the monitoring of these patients.


Population-level changes to promote cardiovascular health.
Cardiovascular diseases (CVD) cause 1.8 million premature (<75 years) death annually in Europe. The majority of these deaths are preventable with the most efficient and cost-effective approach being on the population level. The aim of this position paper is to assist authorities in selecting the most adequate management strategies to prevent CVD. Experts reviewed and summarized the published evidence on the major modifiable CVD risk factors: food, physical inactivity, smoking, and alcohol. Population-based preventive strategies focus on fiscal measures (e.g. taxation), national and regional policies (e.g. smoke-free legislation), and environmental changes (e.g. availability of alcohol). Food is a complex area, but several strategies can be effective in increasing fruit and vegetables and lowering intake of salt, saturated fat, trans-fats, and free sugars. Tobacco and alcohol can be regulated mainly by fiscal measures and national policies, but local availability also plays a role. Changes in national policies and the built environment will integrate physical activity into daily life. Societal changes and commercial influences have led to the present unhealthy environment, in which default option in life style increases CVD risk. A challenge for both central and local authorities is, therefore, to ensure healthier defaults. This position paper summarizes the evidence and recommends a number of structural strategies at international, national, and regional levels that in combination can substantially reduce CVD.


Is the early modulation of brain activity by fearful facial expressions primarily mediated by coarse low spatial frequency information?
Rapidly decoding the emotional content of a face is an important skill for successful social behavior. Several Event Related brain Potential (ERP) have indicated that emotional expressions already influence brain activity as early as 100 ms. Some studies hypothesized that this early brain response to fear depends on coarse-magnocellular inputs, which are primarily driven by Low Spatial Frequency (LSF) cues. Until now however, evidence is inconclusive probably due to the divergent methods used to match luminance and contrast across spatial frequencies and emotional stimuli. In the present study, we measured ERPs to LSF and HSF faces with fearful or neutral expressions when contrast and luminance was matched across SF or not. Our findings clearly show that fearful facial expressions increases the amplitude of P1 (only for contrast-luminance equated images) and N170 in comparison to neutral faces but only in LSF faces, irrespective of contrast or luminance equalization, further suggesting that LSF information plays a crucial role in the early brain responses to fear. Furthermore, we found that, irrespective of luminance or contrast equalization, N170 occurred faster when perceiving LSF faces than HSF faces, again emphasizing the primacy of LSF processing in early face perception.


Allogeneic lymphocytes induce tumor regression of advanced metastatic breast cancer.
Allogeneic T lymphocytes can induce regression of metastatic breast cancer through an immune-mediated graft-versus-tumor (GVT) effect in murine models. To determine if a clinical GVT effect exists against metastatic breast cancer, allogeneic lymphocytes were used as adoptive cellular therapy after a reduced-intensity chemotherapy conditioning regimen and allogeneic hematopoietic stem-cell transplantation (HSCT) from human leukocyte antigen-matched siblings. Sixteen patients with metastatic breast cancer that had progressed after treatment with anthracyclines, taxanes, hormonal agents, and trastuzumab, received allogeneic HSCT. The reduced-intensity transplant conditioning regimen consisted of cyclophosphamide and fludarabine. To distinguish an immunological GVT effect from any antitumor effect of cytotoxic chemotherapy in the transplant-conditioning regimen, allogeneic T lymphocytes were removed from the stem-cell graft and were subsequently administered late postallogeneic HSCT. Allogeneic lymphocytes containing 1 x 10(6), 5 x 10(6), and 10 x 10(6) CD3(+) cells/kg were infused on days +42, +70, and +98 post-allogeneic HSCT, respectively. Objective tumor regressions occurred after day +28 post-allogeneic HSCT in six patients and were attributed to allogeneic lymphocyte infusions. Two of these responding patients had disease progression post-allogeneic HSCT before subsequent tumor regression. Tumor regressions occurred concomitantly with the establishment of complete donor T-lymphoid engraftment, were associated with the development of graft-versus-host disease (GVHD), and were abrogated by subsequent systemic immunosuppression for GVHD. Allogeneic lymphocytes can induce regression of advanced metastatic breast cancer. These results indicate that an immunological GVT effect from allogeneic lymphocytes exists against metastatic breast cancer and provide rationale for further development of allogeneic cellular therapy for this largely incurable disease.


Computational Ligand Descriptors for Catalyst Design.
Ligands, especially phosphines and carbenes, can play a key role in modifying and controlling homogeneous organometallic catalysts, and they often provide a convenient approach to fine-tuning the performance of known catalysts. The measurable outcomes of such catalyst modifications (yields, rates, selectivity) can be set into context by establishing their relationship to steric and electronic descriptors of ligand properties, and such models can guide the discovery, optimization, and design of catalysts. In this review we present a survey of calculated ligand descriptors, with a particular focus on homogeneous organometallic catalysis. A range of different approaches to calculating steric and electronic parameters are set out and compared, and we have collected descriptors for a range of representative ligand sets, including 30 monodentate phosphorus(III) donor ligands, 23 bidentate P,P-donor ligands, and 30 carbenes, with a view to providing a useful resource for analysis to practitioners. In addition, several case studies of applications of such descriptors, covering both maps and models, have been reviewed, illustrating how descriptor-led studies of catalysis can inform experiments and highlighting good practice for model comparison and evaluation.


Time resolved fluorescence tomography of turbid media based on lifetime contrast.
A general linear model for time domain (TD) fluorescence tomography is presented that allows a lifetime-based analysis of the entire temporal fluorescence response from a turbid medium. Simulations are used to show that TD fluorescence tomography is optimally performed using two complementary approaches: A direct TD analysis of a few time points near the peak of the temporal response, which provides superior resolution; and an asymptotic multi-exponential analysis based tomography of the decay portion of the temporal response, which provides accurate localization of yield distributions for various lifetime components present in the imaging medium. These results indicate the potential of TD technology for biomedical imaging with lifetime sensitive targeted probes, and provide useful guidelines for an optimal approach to fluorescence tomography with TD data.


Preventing Peer Violence Against Children: Methods and Baseline Data of a Cluster Randomized Controlled Trial in Pakistan.
Violence against and among children is a global public health problem that annually affects 50% of youth worldwide with major impacts on child development, education, and health including increased probability of major causes of morbidity and mortality in adulthood. It is also associated with the experience of and perpetration of later violence against women. The aim of this article is to describe the intervention, study design, methods, and baseline findings of a cluster randomized controlled trial underway in Pakistan to evaluate a school-based play intervention aiming to reduce peer violence and enhance mental health. A cluster randomized controlled design is being conducted with boys and girls in grade 6 in 40 schools in Hyderabad, Pakistan, over a period of 2 years. The Multidimensional Peer-Victimization and Peer Perpetration Scales and the Children's Depression Inventory 2 (CDI 2) are being used to measure the primary outcomes while investigator-derived scales are being used to assess domestic violence within the family. Specifics of the intervention, field logistics, ethical, and fidelity management issues employed to test the program's impact on school age youth in a volatile and politically unstable country form this report. A total of 1,752 school-age youth were enrolled and interviewed at baseline. Over the preceding 4 weeks, 94% of the boys and 85% of the girls reported 1 or more occurrences of victimization, and 85% of the boys and 66% of the girls reported 1 or more acts of perpetration. Boys reported more depression compared with girls, as well as higher negative mood and self-esteem scores and more interpersonal and emotional problems. Globally, prevalence of youth violence perpetration and victimization is high and associated with poor physical and emotional health. Applying a randomized controlled design to evaluate a peer violence prevention program built on a firm infrastructure and that is ready for scale-up and sustainability will make an important contribution to identifying evidence-informed interventions that can reduce youth victimization and perpetration.


Recovery of brain and plasma cholinesterase activities in ducklings exposed to organophosphorus pesticides.
Brain and plasma cholinesterase (ChE) activities were determined for mallard ducklings (Anas platyrhynchos) exposed to dicrotophos and fenthion. Recovery rates of brain ChE did not differ between ducklings administered a single oral dose vs. a 2-week dietary dose of these organophosphates. Exposure to the organophosphates, followed by recovery of brain ChE, did not significantly affect the degree of brain ChE inhibition or the recovery of ChE activity at a subsequent exposure. Recovery of brain ChE activity followed the general model Y = a + b(logX) with rapid recovery to about 50% of normal, followed by a slower rate of recovery until normal ChE activity levels were attained. Fenthion and dicrotophos-inhibited brain ChE were only slightly reactivated in vitro by pyridine-2-aldoxime methiodide, which suggested that spontaneous reactivation was not a primary method of recovery of ChE activity. Recovery of brain ChE activity can be modeled for interpretation of sublethal inhibition of brain ChE activities in wild birds following environmental applications of organophosphates. Plasma ChE activity is inferior to brain ChE activity for environmental monitoring, because of its rapid recovery and large degree of variation among individuals.


Complementary and integrative health interventions in post-stroke rehabilitation: a systematic PRISMA review.
Researchers have reported measurable improvements in emotional and physical health among adults post-stroke after participating in complementary and integrative health techniques. The aim of this manuscript was to systematically review the effectiveness of active complementary and integrative health interventions as a treatment modality for adults post-stroke. For this review, active interventions were defined as those that required participants to be in control of initiating their own body movement. Five active complementary and integrative health techniques were reviewed and included: Feldenkrais Method, qigong, Pilates, Tai Chi, and yoga. A key word search was conducted in Medline, Cochrane Library, EBSCO, Google Scholar, and PubMed. Inclusion criteria for studies were (1) randomized controlled trials on the effects of active complementary and integrative health interventions, (2) all participants had to be post-stroke, and (3) studies appeared in English in a peer-reviewed journal. Articles in this review included one Qigong, five Pilates, nine Tai Chi, and five yoga studies. All 20 manuscripts reported improvements for participants. Participants in Pilates experienced improvements in quality of life. Improvements in functional balance, standing and dynamic balance, reaction time, maximum excursion, and quality of life were reported in the Pilates studies. Participants in the TC studies experienced a range of positive results including center of gravity, increased reaction time, improved aerobic endurance, fewer falls, sway length and velocity, functional reach, dynamic gait, walking speed, and static and dynamic balance. Improvements after participation in the yoga manuscripts consisted of reduced depression, decreased state and trait anxiety, improved balance, reduction in fear of falling, and enhanced quality of life. Based on the small number of randomized controlled trials, this systematic review reported the effectiveness of four active mind-body interventions for individuals post-stroke. The strongest evidence was for the use of Tai Chi, followed by Pilates and yoga.Implications for rehabilitationClinicians should consider the benefits of qigong, Pilates, Tai Chi, and yoga to best meet individual patient needs and goals.Clinicians who offer qigong, Pilates, Tai Chi, and/or yoga should be qualified to instruct the specific active complementary and integrative health technique or refer patients to those who are qualified.Locate qigong, Pilates, Tai Chi, and yoga classes that are appropriate for people post-stroke in the community to help integrate patients into a program after treatment.


Hints on T cell responses in a fish-parasite model: Enteromyxum leei induces differential expression of T cell signature molecules depending on the organ and the infection status.
Enteromyxum leei is a myxozoan parasite that produces a slow-progressing intestinal disease. This parasite invades the paracellular space of the intestinal epithelium and progresses from the posterior to the anterior intestine. The aim of the present study was to gain insights into fish T cell responses in the gilthead sea bream-E. leei infection model using a PCR-array with 30 signature molecules for different leukocyte responses in head kidney, spleen, anterior and posterior intestine. The PCR-array results suggest that E. leei induced migration of T cells from head kidney to intestines where TH1, CTL and TH17 profiles were activated and kept in balance by the upregulation of regulatory cytokines. These results were partially validated by the use of cross-reacting antibodies and BrdU immunostaining to monitor proliferation. Zap70 immunostaining supported the increased number of T cells in the anterior intestine detected by gene expression, but double staining with BrdU did not show active proliferation of this cell type at a local level, supporting the migration from lymphohaematopoietic tissues to the site of infection. Global analyses of the expression profiles revealed a clear separation between infected and exposed, but non-infected fish, more evident in the target organ. Exposed, non-infected animals showed an intermediate phenotype closer to the control fish. These results evidence a clear modulation of the T cell response of gilthead sea bream upon E. leei infection. The effects occurred both at local and systemic levels, but the response was stronger and more specific at the site of infection, the intestine. Altogether, this research poses a promising basis to understand the response against this important parasite and establish effective preventive or palliative measures.


Linear Atelectasis around the Hilum on Chest Radiography: A Novel Sign of Early Lung Cancer.
Linear atelectasis is a focal area of subsegmental atelectasis with a linear shape. Linear atelectasis may occur as a consequence of subsegmental bronchial obstruction. We propose an early roentgen sign of obstructing lung tumors, namely perihilar linear atelectasis, and ascertain whether this phenomenon could be used as a sign to detect radiographically occult primary lung cancer. We performed a retrospective review of 45,000 posteroanterior chest radiographs to determine the frequency of appearance and characteristics of perihilar linear atelectasis. The perihilar region of chest radiographs was evaluated for the presence of linear atelectasis. When linear atelectasis was found, the total thickness was measured. Student's t-test was used to evaluate statistical significance, correlating the thickness of atelectasis and the presence of obstructing central primary lung cancer. Perihilar linear atelectasis was demonstrated in 58 patients. Atelectasis was caused by an obstructing tumor in 21 (36%) cases and a variety of other conditions in 37 (64%) patients. A statistically significant relationship (P < 0.001) was observed between the dimension of perihilar linear atelectasis and primary lung cancer, with 16 of 19 patients with thick (>5.5 mm) perihilar linear atelectasis found to have primary lung cancer. Thick perihilar linear atelectasis is a new diagnostic roentgen sign that suggests subsegmental bronchial obstruction. In this patient subgroup, who are otherwise asymptomatic, a persistent linear atelectasis can be due to primary lung cancer.


Epidemiology and quarantine measures during COVID-19 outbreak on the cruise ship Diamond Princess docked at Yokohama, Japan in 2020: a descriptive analysis.
The outbreak of coronavirus disease 2019 (COVID-19) on the cruise ship Diamond Princess docked at Yokohama, Japan was highlighted due to its number of cases in the early stage of the global epidemic when the picture of the virus itself, as well as epidemiological characteristics, were being established. We conducted an observational epidemiological study of the outbreak, focusing on a total of 403 individuals who developed a fever of ≥ 37.5°C from 20 January to 22 February 2020. Quarantine measures are also discussed with a descriptive method. Of a total of 3,711 individuals (2,031 males) from 57 countries, 2,666 (71.8%) and 1,045 (28.2%) were passengers and crew with mean age of 66.0 (range: 2-98) and 36.6 (range: 19-64), respectively. Among 403 febrile individuals, 165 passengers and 58 crew members were diagnosed as laboratory-confirmed COVID-19 cases. Until 6 February, the number of confirmed cases was three or less per day. However, distribution of thermometers on 7 February revealed 43 confirmed cases, and it then started decreasing. The outbreak was initiated from decks for passengers and expanded to areas for crew. As of 17 March, when more than14 days had passed after disembarkation of all passengers and crew, there was no report of forming a cluster of infections in Japan from them. At the time of the initiation of quarantine, the outbreak had already expanded to most of the decks from those for passengers, and the results might suggest the contribution of the set of quarantine measures in unprecedented challenges of the control operation.


The role of mesenchymal stem/progenitor cells in sarcoma: update and dispute.
Sarcoma is the collective name for a relatively rare, yet heterogeneous group of cancers, most probably derived from mesenchymal tissues. There are currently over 50 sarcoma subtypes described underscoring the clinical and biologic diversity of this group of malignant cancers. This wide lineage range might suggest that sarcomas originate from either many committed different cell types or from a multipotent cell. Mesenchymal stem/progenitor cells (MSCs) are able to differentiate into many cell types and these multipotent cells have been isolated from several adult human tumors, making them available for research as well as potential beneficial therapeutical agents. Recent accomplishments in the field have broadened our knowledge of MSCs in relation to sarcoma origin and sarcoma treatment in therapeutic settings. However, numerous concerns and disputes have been raised about whether they are the putative originating cells of sarcoma and their questionable role in sarcomagenesis and progression. We summarize the update and dispute about MSC investigations in sarcomas including the definition, cell origin hypothesis, functional and descriptive assays, roles in sarcomagenesis and targeted therapy, with the purpose to give a comprehensive view of the role of MSCs in sarcomas.


Audiogenic seizure prone (asp): a gene affecting behavior in linkage group 8 of the mouse.
The incidence of initial audiogenic seizures in mice from crosses between a susceptible and a resistant inbred strain is attributable to the effects of a single pair of alleles. The locus responsible for this behavioral variation is located in Linkage Group VIII of the mouse. Sensitization-dependent convulsions are influenced in whole or in part by alleles at an independent locus.


Investigating the Therapeutic Mechanism of Cannabidiol in a Human Induced Pluripotent Stem Cell (iPSC)-Based Model of Dravet Syndrome.
Dravet syndrome is an infantile epileptic encephalopathy primarily caused by loss-of-function variants of the gene SCN1A Standard treatment regimens have very limited efficacy to combat the life-threatening seizures in Dravet syndrome or the behavioral-cognitive comorbidities of the disease. Recently there has been encouraging progress in developing new treatments for this disorder. One of the clinical advances is cannabidiol (CBD), a compound naturally found in cannabis and shown to further reduce convulsive seizures in patients when used together with existing drug regimens. Like many other natural products, the exact therapeutic mechanism of CBD remains undefined. Previously we have established a human cellular model of Dravet syndrome by differentiating patient-derived induced pluripotent stem cells (iPSCs) into telencephalic inhibitory and excitatory neurons. Here we have applied this model to investigate the antiepileptic mechanism(s) of CBD at the cellular level. We first determined the effect of escalating the concentrations of CBD on neuronal excitability, using primary culture of rat cortical neurons. We found modulatory effects on excitability at submicromolar concentrations and toxic effects at high concentrations (15 µM). We then tested CBD at 50 nM, a concentration that corresponds to the estimated human clinical exposure, in telencephalic neurons derived from a patient iPSC line and control cell line H9. This 50 nM of CBD increased the excitability of inhibitory neurons but decreased the excitability of excitatory neurons, without changing the amplitude of sodium currents in either cell type. Our findings suggest a cell type-dependent mechanism for the therapeutic action of CBD in Dravet syndrome that is independent of sodium channel activity.


Subcutaneous flexor tendon rupture in patients with rheumatoid arthritis.
We examined the clinical features and functional outcomes of surgically repaired subcutaneous flexor tendon ruptures in patients with rheumatoid arthritis (RA). This retrospective study included 41 fingers of 24 RA patients who underwent surgical treatment for flexor tendon ruptures. Evaluations performed at the time of presentation following rupture were C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and disease activity score in 28 joints (DAS28)-ESR, as well as Larsen grading for carpal bone destruction. The ruptured tendon and postoperative active range of motion (ROM) of digits were also examined. The mean CRP was 2.4 mg/dl, ESR was 52 mm/h, and the DAS28-ESR was 4.5. Carpal bone destruction according to Larsen grade IV-V was observed in 18/24 patients. Affected digits were most commonly the thumb (12) and the ring and little fingers (9 each). Tendon ruptures were most common in the carpal tunnel in zone IV. The mean postoperative finger ROM (flexion/extension) was 38°/2° for the interphalangeal (IP) joint of the thumb and 23°/-2° for the distal interphalangeal joint of the other four fingers. Patients with flexor tendon ruptures present with high disease activity and advanced bone destruction. It is important to reduce the risk of progressive bone destruction and subsequent tendon rupture via tight control of disease activity.


A descriptive study of nonfatal, unintentional home-based injury in urban settings: evidence from Hong Kong.
This study investigates the epidemiological characteristics of non-fatal unintentional household injuries in Hong Kong, the city with the world's highest population density. A population-based, cross-sectional, random telephone survey was conducted with a modified Chinese WHO injury and violence survey questionnarie in May 2007. Descriptive and univariate analysis was conducted to highlight the associated factors. The prevalence of all non-fatal unintentional home injuries in the preceding year was 40.2%. Contusion/crushing injuries, open wounds and burn-related scalds were the most commonly reported home injury and the extremities were the commonest injured body parts. Female gender, younger age and residence in private housing residence were significantly associated with higher likelihood of injuries and most injuries had incurred medical expenses. This is the first study to reported systemtically about the patterns of non-fatal unintentional household injuries in Hong Kong. Future interventions should be targeted to these high risk groups identified in this study.


sp3 carbon-fluorine bond activation in 2,2-difluorohomoallylic alcohols via nucleophilic 5-endo-trig cyclisation: synthesis of 3-fluorinated furan derivatives.
Nucleophilic 5-endo-trig cyclisation was achieved in 2,2-difluorohomoallylic alcohols. Upon treatment with potassium hydride, 2,2-difluorohomoallylic alcohols underwent an intramolecular SN2'-type reaction to afford 3-fluoro-2,5-dihydrofurans in high yields. In addition, the oxidation of these dihydrofurans formed 4-fluorofuran-2(5H)-ones. Thus, ring-fluorinated furan derivatives were efficiently obtained via allylic sp3 carbon-fluorine bond cleavage.


High color rendering white light-emitting-diode illuminator using the red-emitting Eu(2+)-activated CaZnOS phosphors excited by blue LED.
A red phosphor CaZnOS:Eu(2+) was synthesized by solid state reaction and has been evaluated as a candidate for white LEDs. For this material, the XRD, PL, PL excitation (PLE) and diffuse reflection spectra have also been investigated. CaZnOS:Eu(2+) reveals a broad absorption band and good color purity. By utilizing a mixture of red-emitting CaZnOS:Eu(2+), green-emitting (Ba,Sr)(2)SiO(4):Eu(2+) and yellow-emitting Y(3)Al(5)O(12):Ce(3+) as light converters, an intense white InGaN-based blue-LED (~460 nm) was fabricated to exhibit a high color-rendering index Ra of 85 at a correlated color temperature of 4870 K. Based on the results, we are currently evaluating the potential application of CaZnOS:Eu(2+) as a red-emitting blue-chip convertible phosphor.


Restoration of red mud deposits by naturally growing vegetation.
Disposal of red mud (RM) poses serious environmental problems such as wind erosion, air and water pollution. To overcome these problems, effective restoration of the disposal land through naturally growing vegetation is a sustainable and economical approach. The present study involved estimation of frequency (F), density (D), abundance (Ab), and important value index (IVI) of natural flora on abandoned RM sites in order to assess their metal toxicity tolerance capacity. Based on visual observations and highest IVI, S. Asper and S. punicea were identified as effective ecological tools for the restoration of barren RM sites. From the study, remarkable differences were observed between non-rhizospheric and rhizospheric RM of both species. These rhizospheric RM analyses confirm the ability of S. asper and S. punicea for enhancing the biological activities of abandoned RM. Translocation factor (TF) of iron was maximum (2.58) in S. asper, and bioconcentration factor (BCF) was found maximum (1.25) in S. punicea, but both TF (2.58) and BCF (1.35) were high in S. asper. Therefore, this plant could be reported as an iron hyperaccumulator plant. These results suggest that these plant species can be exploited for effective restoration of RM deposited land without any inputs or maintenance.


Intake of Potatoes Is Associated with Higher Diet Quality, and Improved Nutrient Intake and Adequacy among US Adolescents: NHANES 2001-2018 Analysis.
Potatoes are nutrient rich white vegetables, however, research on their impact on public health is limited. The objective of this study was to provide updated evaluation of the cross-sectional association between potato consumption and diet quality, nutrient intake and adequacy. Twenty-four hour diet recall data from adolescents (n = 16,633; age 9-18 years) were used to assess intakes. Usual intakes of nutrients were determined using the National Cancer Institute method and diet quality was calculated using the Healthy Eating Index-2015 (HEI-2015) after adjusting for demographic factors. Consumers of potatoes (baked or boiled potatoes, mashed potatoes and potato mixtures, fried potatoes, and potato chips) had higher (p < 0.05) HEI-2015 total score and subcomponent scores for total vegetables, total protein foods, and refined grain than non-consumers. Consumers also had higher (p < 0.05) intake of energy, dietary fiber, protein, copper, magnesium, phosphorus, potassium, selenium, sodium, zinc, niacin, vitamin B6, vitamin C, vitamin K and total choline; and higher (p < 0.05) adequacy for protein, copper, magnesium, phosphorus, potassium, zinc, thiamine, niacin, vitamin B6, vitamin C, and vitamin K than non-consumers. In conclusion, adolescent potato consumption was associated with higher diet quality, nutrient intake, and adequacy and therefore encouraging their consumption may be an effective strategy for improving nutritional status.


Endovascular and Hybrid Revascularization for Complicated Aorto-Iliac Occlusive Disease: Short-Term Results in Single Institute Experience.
Treatment for extensive aortoiliac occlusive disease (AIOD) includes endovascular interventions, hybrid procedures and surgical reconstruction. This study evaluated the short-term outcomes of endovascular and hybrid procedures in patients with Trans-Atlantic Inter-Society Consensus II (TASC-II) D AIOD lesions. From January 2013 to June 2015, 41 patients with TASC-II D AIOD lesions who underwent revascularization at our institute were retrospectively included. Nineteen underwent endovascular procedures and 22 underwent hybrid procedures with a postoperative surveillance program for at least 1 year. Patient demographics and short-term outcomes were analyzed. The procedural success rate in all patients was 100%. The accumulative postoperative complication rate was 20.2%, and the major complication was acute kidney injury (14.6%). The time of freedom from target lesion revascularization was 18.9 months. The primary patency rates in the endovascular group were 89.5% and 84.2% at 1 and 2 years, respectively, compared to 95.5% at 1 and 2 years in the hybrid group; however, the difference was not significant (p = 0.234). The secondary patency rates were 94.7% and 93% at 1 and 2 years, respectively, in the endovascular group, and 95.5% and 94% at 1 and 2 years, respectively, in the hybrid group; however, the differences was not significant (p = 0.916). Our study revealed that endovascular and hybrid procedures are favorable treatment choices for patients with TASC-II D AIOD lesions. In patients with multilevel steno-occlusive lesions, hybrid procedures improved distal runoff flow and reduced the complexity of endovascular procedures.


DNA binding and synapsis by the large C-terminal domain of phiC31 integrase.
The integrase (Int) from phage C31 acts on the phage and host-attachment sites, attP and attB, to form an integrated prophage flanked by attL and attR. Excision (attL x attR recombination) is prevented, in the absence of accessory factors, by a putative coiled-coil motif in the C-terminal domain (CTD). Int has a serine recombinase N-terminal domain, required for synapsis of recombination substrates and catalysis. We show here that the coiled-coil motif mediates protein-protein interactions between CTDs, but only when bound to DNA. Although the histidine-tagged CTD (hCTD) was monomeric in solution, hCTD bound cooperatively to three of the recombination substrates (attB, attL and attR). Furthermore, when provided with attP and attB, hCTD brought these substrates together in a synaptic complex. Substitutions in the coiled-coil motif that greatly reduce Int integration activity, L460P and Y475H, prevented CTD-CTD interactions and led to defective DNA binding and no detectable DNA synapsis. A substitution, E449K, in full length Int confers the ability to perform excision in addition to integration as it has gained the ability to synapse attL x attR. hCTD(E449K) was similar to hCTD in DNA binding but unable to form the CTD synapse suggesting that the CTD synapse is not essential but could be part of the mechanism that controls directionality.


Comorbidity Between Anorexia Nervosa and Depressive Disorder: A Narrative Review.
Anorexia nervosa (AN) is a disorder with a significantly high prevalence. Affective disorders, including depressive disorder (DD), often coexist with this eating disorder (ED). In this review we will focus on its prevalence, associated vulnerability factors, clinical manifestations, possible etiological factors and its prognosis. A bibliographic search was carried out in the PubMed database selecting those articles that approached the subject of comorbidity between AN and DD. The search was limited to articles published from January 1990 to December 2021. Of the 1891 abstracts reviewed, 33 studies met inclusion criteria. The prevalence of this comorbidity was extremely variable between studies, which exposed their heterogeneity. As to symptomatology this comorbidity presents itself with more severity, greater expression of psychological traits and greater cognitive impairment. Certain personality traits are postulated as vulnerability factors. Genetic factors such as neurochemicals seem to be involved in its pathogenesis. The comorbidity between DD and ED have important influence in its symptomatic expression, severity and prognosis. Some of the analyzed studies provide consistent data, but there are others that are contradictory. It would be necessary to increase the number of studies and use a unified methodology.


A universal scaling relationship between body mass and proximal limb bone dimensions in quadrupedal terrestrial tetrapods.
Body size is intimately related to the physiology and ecology of an organism. Therefore, accurate and consistent body mass estimates are essential for inferring numerous aspects of paleobiology in extinct taxa, and investigating large-scale evolutionary and ecological patterns in the history of life. Scaling relationships between skeletal measurements and body mass in birds and mammals are commonly used to predict body mass in extinct members of these crown clades, but the applicability of these models for predicting mass in more distantly related stem taxa, such as non-avian dinosaurs and non-mammalian synapsids, has been criticized on biomechanical grounds. Here we test the major criticisms of scaling methods for estimating body mass using an extensive dataset of mammalian and non-avian reptilian species derived from individual skeletons with live weights. Significant differences in the limb scaling of mammals and reptiles are noted in comparisons of limb proportions and limb length to body mass. Remarkably, however, the relationship between proximal (stylopodial) limb bone circumference and body mass is highly conserved in extant terrestrial mammals and reptiles, in spite of their disparate limb postures, gaits, and phylogenetic histories. As a result, we are able to conclusively reject the main criticisms of scaling methods that question the applicability of a universal scaling equation for estimating body mass in distantly related taxa. The conserved nature of the relationship between stylopodial circumference and body mass suggests that the minimum diaphyseal circumference of the major weight-bearing bones is only weakly influenced by the varied forces exerted on the limbs (that is, compression or torsion) and most strongly related to the mass of the animal. Our results, therefore, provide a much-needed, robust, phylogenetically corrected framework for accurate and consistent estimation of body mass in extinct terrestrial quadrupeds, which is important for a wide range of paleobiological studies (including growth rates, metabolism, and energetics) and meta-analyses of body size evolution.


[Translation and construct validity of the Lequesne index for Arab speaking North African patients with osteoarthritis of the knee].
To translate in Arabic and validate the Lequesne index for use in Tunisian. No instrument wording in Arabic language and validated in an Arab population to measure lower limb functional disability caused by OA. Arab translation was obtained using the "forward translation/backward translation" method. Adaptations were made after a pilot study. Patients with symptomatic knee osteoarthritis fulfilling the revised criteria of the American College of Rheumatology were included. Impairment outcome measures (VAS pain; knee mobility; Kellgren's radiological score); disability (the maximum distance walked; WOMAC index) and Beck depression scale were recorded. Inter rater reliability was assessed using the intra-class correlation coefficient (ICC) and the Bland and Altman method. Construct validity was investigated using the Spearman rank correlation coefficient (convergent and divergent validities) and a factor analysis was performed. Internal consistency of each factor was assessed by Crohnbach alpha coefficient. One hundred and three patients were included. All questions were acceptable and retained. Inter rater reliability was excellent with ICC = 0.91. The Bland and Altman method showed distribution of differences homogenous and no systematic trend. Expected divergent validity and convergent validity were observed, suggested good construct validity. Two main factors were extracted by factor analysis of the Lequesne, and explained more than 55% of the cumulative variance, the first factor represents disability and the second represents pain and stiffness. Crohnbach alpha coefficient was, respectively, 0.68 for factor 1 and 0.54 for factor 2. In conclusion, we translated and adapted the Lequesne index into Arabic to suit Tunisian people. Translated questionnaire is reliable and valid. Although the scale was validated in a Tunisian population, we expect that it can suit other Arab populations especially North Africans. Further studies are needed to confirm such hypothesis.


"Not one of us": predictors and consequences of denying ingroup characteristics to ambiguous targets.
We investigated individual difference predictors of ascribing ingroup characteristics to negative and positive ambiguous targets. Studies 1 and 2 investigated events involving negative targets whose status as racial (Tsarnaev brothers) or national (Woolwich attackers) ingroup members remained ambiguous. Immediately following the attacks, we presented White Americans and British individuals with the suspects' images. Those higher in social dominance orientation (SDO) and right-wing authoritarianism (RWA)-concerned with enforcing status boundaries and adherence to ingroup norms, respectively-perceived these low status and low conformity suspects as looking less White and less British, thus denying them ingroup characteristics. Perceiving suspects in more exclusionary terms increased support for treating them harshly, and for militaristic counter-terrorism policies prioritizing ingroup safety over outgroup harm. Studies 3 and 4 experimentally manipulated a racially ambiguous target's status and conformity. Results suggested that target status and conformity critically influence SDO's (status) and RWA's (conformity) effects on inclusionary versus exclusionary perceptions.


Differential splicing of KLK5 and KLK7 in epithelial ovarian cancer produces novel variants with potential as cancer biomarkers.
The wild-type or variant mRNAs of several kallikrein (KLK) genes, such as KLK4, are highly expressed in ovarian carcinomas and may have potential as tumor markers. Two of these KLK genes (KLK5 and KLK7) and their proteins (hK5 and hK7) were first identified in the skin epidermis, where hK5 may be the physiological activator of hK7. The purpose of this study was to reexamine the expression of KLK5/hK5 and KLK7/hK7 and their association and to determine whether cancer-related variant transcripts were expressed. The expression of KLK5/hK5 and KLK7/hK7 was analyzed in the same cohort (n = 37) of benign (n = 4) and malignant ovarian tissue (n = 23) samples and primary cultured cells (n = 21) and in 8 ovarian cancer cell lines using semiquantitative RT-PCR; Southern, Northern, and Western blot analyses; and immunohistochemistry techniques. We showed the concordant higher expression of both KLK5/hK5 and KLK7/hK7 in ovarian carcinomas, especially late-stage serous carcinomas, compared with normal ovaries and benign adenomas. We also found that one novel KLK5 transcript with a short 5'-untranslated region and a novel KLK7 transcript with a long 3'-untranslated region were highly expressed in the ovarian cancer cell lines OVCAR-3 and PEO1, respectively, but were expressed at very low levels in normal ovarian epithelial cells. Both Western blot and immunohistochemistry analyses showed that these two enzymes are secreted from ovarian carcinoma cells. Our study demonstrated that hK5 and hK7, or more specifically, the short KLK5 and long KLK7 transcripts, may be useful as tumor markers for epithelial-derived serous carcinomas. However, additional clinical studies assessing serum levels of these putative biomarkers are required to confirm their usefulness in the diagnosis and/or monitoring of these tumors.


Enhanced chloroplast transgene expression in a nuclear mutant of Chlamydomonas.
Chloroplast transformation in microalgae offers great promise for the production of proteins of pharmaceutical interest or for the development of novel biofuels. For many applications, high level expression of transgenes is desirable. We have transformed the chloroplast of Chlamydomonas reinhardtii with two genes, acrV and vapA, which encode antigens from the fish pathogen Aeromonas salmonicida. The promoters and 5' untranslated regions of four chloroplast genes were compared for their ability to drive expression of the bacterial genes. The highest levels of expression were obtained when they were placed under the control of the cis-acting elements from the psaA-exon1 gene. The expression of these chimeric genes was further increased when a nuclear mutation that affects a factor involved in psaA splicing was introduced in the genetic background of the chloroplast transformants. Accumulation of both the chimeric mRNAs and the recombinant proteins was dramatically increased, indicating that negative feedback loops limit the expression of chloroplast transgenes. Our results demonstrate the potential of manipulating anterograde signalling to alter negative regulatory feedback loops in the chloroplast and improve transgene expression.


The Effect of Selenium on Ischemia-Reperfusion Injury: An Experimental Study on a Transverse Rectus Abdominis Musculocutaneous Flap Model.
The aim of this study is to investigate effects of selenium and enlighten the possible mechanism of action in a rat transverse musculocutaneous flap model following ischemia-reperfusion injury. In this study, an experimental model, which mimicked free tissue transfer, was applied. Twenty-four male Wistar Albino rats were divided into a control group (N = 12), and a selenium treated group (N = 12). A superiorly based transverse rectus abdominis musculocutaneous (TRAM) flap was elevated and an ischemic insult for 4 hours was given. In selenium treated group (Group 2), sodium selenite (0.625 mg/kg) was injected intraperitoneally (i.p), 2 hours before the induction of ischemia. Six rats from each group were sacrificed at 24 hours after the operation and malonyldialdehyde (MDA), nitric oxide (NO), and glutathione (GSH) levels were measured biochemically, whereas the intensity of neutrophil infiltration was evaluated. For the rest of the rats in Group 2, sodium selenite was injected at the same dose everyday to the postoperative 10th day, in which the remaining 6 rats from each group were sacrificed. On postoperative 10th day, flap viability was assessed along with the evaluation of intensity of neovascularization. In Group 1, MDA levels were higher significantly (P < 0.05) when compared with Group 2. No statistical difference, however, was found for NO (P > 0.05), and GSH (P > 0.05) levels among Group 1 and 2. Neutrophil infiltration was more intense in Group 1, when compared with Group 2 whereas neovascularization was more abundant in samples of Group 2. Group 2 shows higher average flap surface areas when compared with Group 1 (P < 0.05). The results of this study demonstrated the preventive effect of selenium against ischemia-reperfusion injury by reducing tissue necrosis in muscle flaps possibly by decreasing MDA, increasing neovascularization, and decreasing neutrophil infiltration, thus suppressing inflammation.


Association between health-service use and multiplex genetic testing.
The objective of this work was to examine whether offers of multiplex genetic testing increase health-care utilization among healthy patients aged 25-40 years. The identification of genetic variants associated with common disease is accelerating rapidly. "Multiplex tests" that give individuals feedback on large panels of genetic variants have proliferated. Availability of these test results may prompt consumers to use more health-care services. A total of 1,599 continuously insured adults aged 25-40 years were surveyed and offered a multiplex genetic susceptibility test for eight common health conditions. Health-care utilization from automated records was compared in 12-month pre- and posttest periods among persons who completed a baseline survey only (68.7%), those who visited a study website but opted not to test (17.8%), and those who chose the multiplex genetic susceptibility test (13.6%). In the pretest period, persons choosing genetic testing used an average of 1.02 physician visits per quarter as compared with 0.93 and 0.82 for the baseline-only and Web-only groups, respectively (P < 0.05). There were no statistically significant differences by group in the pretest use of any common medical tests or procedures associated with four common health conditions. When changes in physician and medical test/procedure use in the posttest period were compared among the groups, no statistically significant differences were observed for any utilization category. Persons offered and completing multiplex genetic susceptibility testing used more physician visits before testing, but testing was not associated with subsequent changes in use. This study supports the supposition that multiplex genetic testing offers can be provided directly to the patients in such a way that use of health services is not inappropriately increased.


Poly(A)-binding protein-interacting protein 1 binds to eukaryotic translation initiation factor 3 to stimulate translation.
Poly(A)-binding protein (PABP) stimulates translation initiation by binding simultaneously to the mRNA poly(A) tail and eukaryotic translation initiation factor 4G (eIF4G). PABP activity is regulated by PABP-interacting (Paip) proteins. Paip1 binds PABP and stimulates translation by an unknown mechanism. Here, we describe the interaction between Paip1 and eIF3, which is direct, RNA independent, and mediated via the eIF3g (p44) subunit. Stimulation of translation by Paip1 in vivo was decreased upon deletion of the N-terminal sequence containing the eIF3-binding domain and upon silencing of PABP or several eIF3 subunits. We also show the formation of ternary complexes composed of Paip1-PABP-eIF4G and Paip1-eIF3-eIF4G. Taken together, these data demonstrate that the eIF3-Paip1 interaction promotes translation. We propose that eIF3-Paip1 stabilizes the interaction between PABP and eIF4G, which brings about the circularization of the mRNA.


The development of mature B lymphocytes requires the combined function of CD19 and the p110δ subunit of PI3K.
Mice lacking either CD19 or p110δ have reduced numbers of marginal zone and B1 B cells but normal numbers of naïve B2 cells which occupy the follicles of the lymphoid organs. We show here that mice lacking both CD19 and p110δ have normal B cell development in the bone marrow but have a significant reduction in the number of naïve B2 cells in the bone marrow, spleen and lymph nodes. These p110δ/CD19 double mutant B cells show a survival defect and reduced responsiveness to the pro-survival cytokine BAFF despite normal NFκB2/p100 processing and elevated expression of Bcl-2. Although the combined loss of p110δ and CD19 did not increase switching to Ig-lambda in immature B cells, mature B lymphocytes from the lymph nodes of p110δ/CD19 double mutant mice express highly elevated levels of mRNA encoding RAG-1 and RAG-2, which confirms the existing synergy between CD19 and p110δ-mediated signaling.


Costs of illness due to endemic cholera.
Economic analyses of cholera immunization programmes require estimates of the costs of cholera. The Diseases of the Most Impoverished programme measured the public, provider, and patient costs of culture-confirmed cholera in four study sites with endemic cholera using a combination of hospital- and community-based studies. Families with culture-proven cases were surveyed at home 7 and 14 days after confirmation of illness. Public costs were measured at local health facilities using a micro-costing methodology. Hospital-based studies found that the costs of severe cholera were US$32 and US$47 in Matlab and Beira. Community-based studies in North Jakarta and Kolkata found that cholera cases cost between US$28 and US$206, depending on hospitalization. Patients' cost of illness as a percentage of average monthly income were 21% and 65% for hospitalized cases in Kolkata and North Jakarta, respectively. This burden on families is not captured by studies that adopt a provider perspective.


Marine extinction risk shaped by trait-environment interactions over 500 million years.
Perhaps the most pressing issue in predicting biotic responses to present and future global change is understanding how environmental factors shape the relationship between ecological traits and extinction risk. The fossil record provides millions of years of insight into how extinction selectivity (i.e., differential extinction risk) is shaped by interactions between ecological traits and environmental conditions. Numerous paleontological studies have examined trait-based extinction selectivity; however, the extent to which these patterns are shaped by environmental conditions is poorly understood due to a lack of quantitative synthesis across studies. We conducted a meta-analysis of published studies on fossil marine bivalves and gastropods that span 458 million years to uncover how global environmental and geochemical changes covary with trait-based extinction selectivity. We focused on geographic range size and life habit (i.e., infaunal vs. epifaunal), two of the most important and commonly examined predictors of extinction selectivity. We used geochemical proxies related to global climate, as well as indicators of ocean acidification, to infer average global environmental conditions. Life-habit selectivity is weakly dependent on environmental conditions, with infaunal species relatively buffered from extinction during warmer climate states. In contrast, the odds of taxa with broad geographic ranges surviving an extinction (>2500 km for genera, >500 km for species) are on average three times greater than narrow-ranging taxa (estimate of odds ratio: 2.8, 95% confidence interval = 2.3-3.5), regardless of the prevailing global environmental conditions. The environmental independence of geographic range size extinction selectivity emphasizes the critical role of geographic range size in setting conservation priorities.


Heatstroke Effect on Brain Heme Oxygenase-1 in Rats.
Exposure to high environmental temperature leading to increased core body temperature above 40°C and central nervous system abnormalities such as convulsions, delirium, or coma is defined as heat stroke. Studies in humans and animals indicate that the heat shock responses of the host contribute to multiple organ injury and death during heat stroke. Heme oxygenase-1 (HO-1)-a stress-responsive enzyme that catabolizes heme into iron, carbon monoxide, and biliverdin-has an important role in the neuroprotective mechanism against ischemic stroke. Here, we investigated the role of endogenous HO-1 in heat-induced brain damage in rats. RT-PCR results revealed that levels of HO-1 mRNA peaked at 0 h after heat exposure and immunoblot analysis revealed that the maximal protein expression occurred at 1 h post-heat exposure. Subsequently, we detected the HO-1 expression in the cortical brain cells and revealed the neuronal cell morphology. In conclusion, HO-1 is a potent protective molecule against heat-induced brain damage. Manipulation of HO-1 may provide a potential therapeutic approach for heat-related diseases.


Incidence of health of the nation cancers by social class.
Using data from the Longitudinal Study social class patterns in the incidence of breast, lung and cervical cancer in women, and lung cancer in men, for the period 1976-89 were examined. At working ages, 15 to 64, there was very little difference in breast cancer incidence between women in non-manual and manual classes. At older ages the incidence was higher in women in non-manual classes than in those in manual classes. Cervical cancer incidence was considerably higher among younger women in manual than in non-manual classes and these differences were greatest in 1986-89. Among both younger and older men and women, strong class differentials in the incidence of lung cancer were evident in 1986-89. These findings indicate the need to target prevention strategies sensitively and to ensure equitable access to services.


The use of whole organ decellularization for the generation of a vascularized liver organoid.
A major roadblock to successful organ bioengineering is the need for a functional vascular network within the engineered tissue. Here, we describe the fabrication of three-dimensional, naturally derived scaffolds with an intact vascular tree. Livers from different species were perfused with detergent to selectively remove the cellular components of the tissue while preserving the extracellular matrix components and the intact vascular network. The decellularized vascular network was able to withstand fluid flow that entered through a central inlet vessel, branched into an extensive capillary bed, and coalesced into a single outlet vessel. The vascular network was used to reseed the scaffolds with human fetal liver and endothelial cells. These cells engrafted in their putative native locations within the decellularized organ and displayed typical endothelial, hepatic, and biliary epithelial markers, thus creating a liver-like tissue in vitro. These results represent a significant advancement in the bioengineering of whole organs. This technology may provide the necessary tools to produce the first fully functional bioengineered livers for organ transplantation and drug discovery.