Miracle-dz/UniFAR-FTUs huggingface dataset:
Recombinant Vitronectin Is a Functionally Defined Substrate That Supports Human Embryonic Stem Cell Self‐Renewal via αVβ5 Integrin

Defined growth conditions are essential for many applications of human embryonic stem cells (hESC). Most defined media are presently used in combination with Matrigel, a partially defined extracellular matrix (ECM) extract from mouse sarcoma. Here, we defined ECM requirements of hESC by analyzing integrin expression and ECM production and determined integrin function using blocking antibodies. hESC expressed all major ECM proteins and corresponding integrins. We then systematically replaced Matrigel with defined medium supplements and ECM proteins. Cells attached efficiently to natural human vitronectin, fibronectin, and Matrigel but poorly to laminin + entactin and collagen IV. Integrin‐blocking antibodies demonstrated that αVβ5 integrins mediated adhesion to vitronectin, α5β1 mediated adhesion to fibronectin, and α6β1 mediated adhesion to laminin + entactin. Fibronectin in feeder cell‐conditioned medium partially supported growth on all natural matrices, but in defined, nonconditioned medium only Matrigel or (natural and recombinant) vitronectin was effective. Recombinant vitronectin was the only defined functional alternative to Matrigel, supporting sustained self‐renewal and pluripotency in three independent hESC lines.
PS2 mutation increases neuronal cell vulnerability to neurotoxicants through activation of caspase-3 by enhancing of ryanodine receptor-mediated calcium release.

SPECIFIC AIMSTo determine neurotoxic mechanisms of PS2 mutation, disruption of cellular calcium homeostasis through ryanodine receptor pathway, interaction between PS2 and ryanodine receptor, and sensitization of neurons to neurotoxicants by activation of caspase-3 activity were investigated in the stably transfected PC12 cells and cortical neurons from transgenic mice expressing wild or mutant PS2 (N141I). PRINCIPAL FINDINGS1. Increased vulnerability, intracellular calcium level, and colocalization of RyR and PS2 in the neuronal cells expressing mutant PS2PC12 cells expressing mutant PS2 and cortical neurons from mutant PS2 transgenic mice were significantly more vulnerable against L-glutamate and Aβ treatment compared with PC12 cells expressing wild-type (WT) PS2, and cortical neurons from WT PS2 mice, as determined by MTT reduction assay in the PC12 cells, and by Trypan blue staining in cortical neuron or DAPI staining (data not shown). To determine whether PS2 mutations increase calcium release and the.
Outcomes following chronic obstructive pulmonary disease presentations to emergency departments in Alberta: a population-based study.

INTRODUCTION Chronic obstructive pulmonary disease (COPD) is a complex, multisystem disorder that often results in exacerbations requiring emergency department (ED) management. Following an exacerbation and discharge from the ED, reassessment and management adjustment with a health care provider are recommended to re-establish control of the disease. OBJECTIVES To describe outcomes of all COPD presentations to EDs made by adults in Alberta including the time spent in the ED and the physician visits following the ED visit. METHODS Provincial administrative databases were used to obtain all ED encounters for COPD during six fiscal years (1999 to 2005). The information extracted included demographics, ED visit timing, and acute and subacute outcomes (physician visits up to 365 days after discharge for all 7302 discharged individuals during a one-year period). Data analysis included descriptive summaries and survival curves. RESULTS There were 85,330 ED visits for acute COPD, of which 67% were discharged from the ED. Median ED length of stay was longer in large urban areas (Calgary: 5 h 9 min; Edmonton: 4 h 58 min) than in other regions of Alberta (1 h 17 min). Admissions resulted from 32% of visits and varied among regions; however, few were admitted to the intensive care unit (1%) or died (0.1%). Following discharge, the median time to first follow-up with a physician was 13 days; however, only 40% of patients had follow-up visits in the first seven days. Repeat ED visits within seven days occurred in 5.7% of discharged patients, while 25.6% of discharged patients had repeat ED visits within 365 days of discharge. CONCLUSIONS More than 30% of COPD ED visits resulted in admission; regional variation was significant. Moreover, discharged patients experienced delayed follow-up and often required repeat ED visits. Interventions to improve reassessment and reduce COPD-related repeat ED visits should be explored.
Gender Differences and Psychopathological Features Associated With Addictive Behaviors in Adolescents

Background The aims of the study were to assess prevalence and gender differences of addictive behaviors (substance- and non-substance-related) in an adolescent population, and their association with psychopathological features and academic performance. Material and methods A sample of high school Italian students (n = 996; M = 240, F = 756) was examined using a self-report survey concerning sociodemographic characteristics, cigarette smoking, alcohol and substance use, perceived academic performance, activities, and behaviors (Internet use, gambling, and physical exercising). The Internet Addiction Test, the South Oaks Gambling Screen-revised Adolescent, and the Exercise Addiction Inventory-Short Form were administered to identify problematic behaviors. The Barratt Impulsiveness Scale for Adolescent, the Snaith–Hamilton Pleasure Scale, the Dissociative Experience Scale for Adolescent, and the Toronto Alexithymia Scale were used to investigate psychopathological dimensions. Results Frequent alcohol intake and lifetime substances consumption were more common among males. The occurrence of other addictive behaviors was 22.1% for problematic Internet use (M = F), 9.7% for at-risk/problematic gambling (M > F), and 6.2% for maladaptive physical exercise (M = F). We also found an association between substance-/non-substance-related addictive behaviors and psychopathological dimensions. Addictive behaviors were more frequent among students reporting poor school performance. Conclusion Our study showed a relevant prevalence of addictive behaviors in a sample of Italian high school students, with specific gender differences. We underlined the cooccurrence of substance and non-substance-related addictive behaviors, and their association with worse school performance. Dissociative proneness, anhedonia, alexithymia, and impulsivity were associated with addictive behaviors in adolescents and might represent vulnerability factors for the development of psychiatric disorders in adulthood. A better understanding of psychopathological features associated with addictive behaviors might be useful for the prevention/early intervention.
Suicide notes: what do they tell us?

Police investigation records of all suicide cases in 1992 (n= 769) and the suicide notes that had been left (224 notes for 154 subjects) were examined. Note‐leavers were characterized as young females, of non‐widowed marital status, with no history of previous suicide attempts, no previous psychiatric illness, and with religious beliefs. Suicide notes written by young people were longer, rich in emotions, and often begging for forgiveness. Suicide notes written by the elderly were shorter, contained specific instructions, and were less emotional. A significant proportion of note‐leavers did mention their difficulties. Suicide notes may serve some explanatory purpose and may have a therapeutic role in helping the surviving relatives to understand the suicide. A knowledge of the messages contained within suicide notes could be useful for suicide prevention programmes. The significance of suicide notes is best understood within the context of the occurrence of suicides.
Simulation of propagation along a cylindrical bundle of cardiac tissue. I. Mathematical formulation

A mathematical description, based on a three-dimensional model for studying propagation in cardiac muscle is given. The model makes use of the bidomain concept to construct a representation of a cylindrical, multicellular bundle lying in an extensive volume conductor. The equations for the cylindrical bidomain are derived for different combinations of boundary conditions and simplifying assumptions. The analysis shows that an analytic model for propagation can be set up if one assumes that the ratio of the intracellular and interstitial bidomain conductivities in the radial and axial direction are the same (i.e. equal anisotropy) and the intracellular radial current density vanishes at the surface. As a point of reference, the classical one-dimensional cable model is also examined and the expressions governing propagation are reformulated to account for the extracellular medium, a factor ignored in most simulation studies. <<ETX>>
Concurrent Infection with an Intestinal Helminth Parasite Impairs Host Resistance to Enteric Citrobacter rodentium and Enhances Citrobacter-Induced Colitis in Mice

ABSTRACT Infections with intestinal helminth and bacterial pathogens, such as enteropathogenic Escherichia coli, continue to be a major global health threat for children. To test the hypothesis that intestinal helminth infection may be a risk factor for enteric bacterial infection, a murine model was established by using the intestinal helminth Heligomosomoides polygyrus. To analyze the modulatory effect of a Th2-inducing helminth on the outcome of enteric bacterium Citrobacter rodentium infection, BALB/c and STAT 6 knockout (KO) mice were infected with H. polygyrus, C. rodentium, or both. We found that only BALB/c mice coinfected with H. polygyrus and C. rodentium displayed a marked morbidity and mortality. The enhanced susceptibility to C. rodentium and intestinal injury of coinfected BALB/c mice were shown to be associated with a significant increase in helminth-driven Th2 responses, mucosally and systemically, and correlated with a significant downregulation of protective gamma interferon and with a dramatic upregulation of the proinflammatory tumor necrosis factor alpha response. In addition, C. rodentium-associated colonic pathology in coinfected BALB/c mice was significantly enhanced, whereas bacterial burden was increased and clearance was delayed. In contrast, coinfection in STAT 6 KO mice failed to promote C. rodentium infection or to induce a more severe intestinal inflammation and tissue injury, demonstrating a mechanism by which helminth influences the development of host protective immunity and susceptibility to bacterial infections. We conclude that H. polygyrus coinfection can promote C. rodentium-associated disease and colitis through a STAT 6-mediated immune mechanism.
Deoxynucleic Acids from Cryptococcus neoformans Activate Myeloid Dendritic Cells via a TLR9-Dependent Pathway1

The mechanism of host cell recognition of Cryptococcus neoformans, an opportunistic fungal pathogen in immunocompromised patients, remains poorly understood. In the present study, we asked whether the DNA of this yeast activates mouse bone marrow-derived myeloid dendritic cells (BM-DCs). BM-DCs released IL-12p40 and expressed CD40 upon stimulation with cryptococcal DNA, and the response was abolished by treatment with DNase, but not with RNase. IL-12p40 production and CD40 expression were attenuated by chloroquine, bafilomycin A, and inhibitory oligodeoxynucleotides (ODN) that suppressed the responses caused by CpG-ODN. Activation of BM-DCs by cryptococcal DNA was almost completely abrogated in TLR9 gene-disrupted (TLR9−/−) mice and MyD88−/− mice, similar to that by CpG-ODN. In addition, upon stimulation with whole yeast cells of acapsular C. neoformans, TLR9−/− BM-DCs produced a lower amount of IL-12p40 than those from wild-type mice, and TLR9−/− mice were more susceptible to pulmonary infection with this fungal pathogen than wild-type mice, as shown by increased number of live colonies in lungs. Treatment of cryptococcal DNA with methylase resulted in reduced IL-12p40 synthesis by BM-DCs. Furthermore, using a luciferase reporter assay, cryptococcal DNA activated NF-κB in HEK293 cells transfected with the TLR9 gene. Finally, confocal microscopy showed colocalization of fluorescence-labeled cryptococcal DNA with CpG-ODN and the findings merged in part with the distribution of TLR9 in BM-DCs. Our results demonstrate that cryptococcal DNA causes activation of BM-DCs in a TLR9-dependent manner and suggest that the CpG motif-containing DNA may contribute to the development of inflammatory responses after infection with C. neoformans.
Immunization coverage and its determinants among children 12-23 months of age in Aden, Yemen.

I am pleased to know that high immunization coverage (83.1%) is achieved in children 12-23 months of age in Aden, Yemen.1 However, the remaining 16.9% of children who did not have complete immunization still yield deep concerns. I presume that many reasons generally contribute to parental decline of completing immunizing their children. Non-availability of vaccines, inconvenient time/venue, and being unaware of need for additional doses are well-known reasons. However, parental misbelief on vaccines still represent a major factor contributing to total parental refusal to immunize their children, particularly in developing countries. These might include interference with child’s natural immunity, contradictions with God’s will, being ineffective, and taking the child to the clinic for immunization wastes a lot of time and money. The World Health Organization (WHO) and United Nations International Children’s Emergency Fund (UNICEF) have produced a new Global Immunization Vision and Strategy for 2006-2015, which aims to protect more people of all age groups against more diseases, and set a number of immunization goals.2 Therefore, it would be pertinent to scrutinize real factors hampering immunizing children in Yemen, and institute suitable programs to mitigate these factors towards increasing the immunization coverage to more than 90%. Mahmood D. Al-Mendalawi Department of Pediatrics Al-Kindy College of Medicine Baghdad University Baghdad, Iraq Reply from the Author
The Limitation of DEXA Analysis for Bone Mass Determination in Mice

An increase in femoral and tibio/fibular bone mass following periosteal membrane stimulation by Moloney sarcoma virus inoculation into thigh muscles of mice was measured in situ on formalin fixed excised hind limbs using a Hologic 4500A Fan Beam X-ray bone densitometer adapted for small bone samples. These results were verified by measurements of constant dry bone mass of the same bones liberated from soft limb tissues by NaOH hydrolysis. There was no consistent data correlation found between the DEXA scan and dry bone mass evaluations. It is concluded that the sensitivity of the DEXA measurement is unsuitable when assessing very small bone samples, weighing merely 20-30 mg.
Learning Selection of User Generated Event Videos

User generated images and videos can enhance the coverage of live events on social and online media, as well as in broadcasts. However, the quality, relevance and complementarity of the received contributions varies greatly. In a live scenario, it is often not feasible for the editorial team to review all content and make selections. We propose to support this work by automatic selection based on captured metadata, and extracted quality and content features. It is usually desired to have a human in the loop, thus the automatic system does not make a final decision, but provides a ranked list of content items. As the operator makes selections, the automatic system shall learn from these decisions, which may change over time. Due to the need for online learning and quick adaptation, we propose the use of online random forests for this task. We show on data from three real live events that the approach is able to provide a ranking based on the predicted selection likelihood after an initial adjustment phase.
Etude dynamique des apports en éléments majeurs et nutritifs des eaux de la lagune de Porto-Novo (Sud Bénin)

Afin dfevaluer le niveau trophique de la lagune qui expliquerait la proliferation des algues sur la lagune, les nutriments (NTK et phosphore total) et la Demande Chimique en Oxygene (DCO) des eaux de la lagune Porto-Novo ont ete determines suivant les quatre saisons de lfannee. Lfetude a egalement permis dfanalyser par chromatographie les elements mineraux, anions et cations, dans les eaux de la lagune. Les resultats ont montre que les concentrations en chlore (variant entre 0,84 et 1180 mg/L) et en sodium (variant entre 35,52 et 7305 mg/L) sont plus elevees au cours de la periode de basses eaux ; les eaux marines arrivent dans la lagune par lfintermediaire du lac Nokoue. Les concentrations obtenues au cours de la periode des basses eaux pour les NTK montrent que le Canal de Totche et la savonnerie de lfIndustrie Beninoise des Corps Gras (IBCG) sont tres riches en NTK. De meme, les concentrations elevees pour le phosphore total et les phosphates sont obtenues au debut de la saison des pluies, la concentration la plus elevee est obtenue a lfIBCG. Les valeurs moyennes annuelles de phosphore total dans les eaux varient de 0,31 mg/L a 6,05 mg/L, elles depassent donc 100 ƒEgP/L : la lagune est donc hypereutrophe selon lfOrganisation de Cooperation et Developpement Economique (OCDE, 1982). Quant aux valeurs moyennes de la DCO, elles varient de 101 mgO2/L a 142 mgO2/L. Les mesures effectuees au cours des differentes periodes de lfannee montrent que les eaux de ruissellement contribuent beaucoup a lfeutrophisation de la lagune. Ceci montre aussi lfurgence de la mise en place dfun systeme de gestion et de controle des eaux usees avant leur deversement dans la lagune.
Adaptation of chondrocytes to low oxygen tension: Relationship between hypoxia and cellular metabolism

In endochondral bone, the growth cartilage is the site of rapid growth. Since the vascular supply to the cartilage is limited, it is widely assumed that cells of the cartilage are hypoxic and that limitations in the oxygen supply regulate the energetic state of the maturing cells. In this report, we evaluate the effects of oxygen tension on chondrocyte energy metabolism, thiol status, and expression of transcription elements, HIF and AP‐1. Imposition of an hypoxic environment on cultured chondrocytes caused a proportional increase in glucose utilization and elevated levels of lactate synthesis. Although we observed a statistical increase in the activities of phosphofructokinase, pyruvate kinase, lactate dehydrogenase, and creatine kinase after exposure to lowered oxygen concentrations, the effect was small. The cultured cells exhibited a decreased utilization of glutamine, possibly due to down regulation of mitochondrial function and inhibition of oxidative deamination. With respect to total energy generation, we noted that these cells are quite capable of maintaining the energy charge of the cell at low oxygen tensions. Indeed, no changes in the absolute quantity of adenine nucleotides or the energy charge ratio was observed. Hypoxia caused a decrease in the glutathione content of cultured chondrocytes and a concomitant rise in cell and medium cysteine levels. It is likely that the fall in cell glutathione level is due to decreased synthesis of the tripeptide under reduced oxygen stress and the limited supply of glutamate. The observed rise in cellular and medium cysteine levels probably reflects an increase in the rate of degradation of glutathione and a decrease in synthesis of the peptide. To explore how cells transduce these metabolic effects, gel retardation assays were used to study chondrocyte HIF and AP‐1 binding activities. Chondrocyte nuclear preparations bound an HIF‐oligonucleotide; however, at low oxygen tensions, no increase in HIF binding was observed. In addition, we found that AP‐1 binding activities in chondrocytes exposed to low oxygen tensions was elevated, although the response was lower than that exhibited by fibroblasts exposed to the same range of oxygen concentrations. We compared these results to HIF and AP‐1 binding by cells in the growth plate. There was strong HIF and AP‐1 binding throughout the plate, but no evidence of selective binding to any one zone. The results of the study lend strong support to the view that chondrocytes are very well adapted to low oxygen tensions; thus, under hypoxic conditions, there is a high level of expression of both HIF and AP‐1, and energy conservation appears to be near‐maximum. © 1996 Wiley‐Liss, Inc.
The safety of polymyxin antibiotics

Introduction: The emergence of multidrug-resistant gram-negative bacteria has led to the increasing use of polymyxins. Nephrotoxicity and, to a lesser degree, neurotoxicity occur often during systemic polymyxin therapy. Scientific evidence regarding safety associated with polymyxins remains limited. Areas covered: Case reports/case series, observational studies and clinical trials assessing safety and toxicity of polymyxins were critically reviewed. Expert opinion: Polymyxins are drugs with a narrow therapeutic range. Nephrotoxicity is associated with both host factors and polymyxin exposure, and recent studies suggest that the relative risk of nephrotoxicity is similar for colistin and polymyxin B. Studies that have examined the safety of polymyxins have several limitations. Considering the available evidence, toxicities that may develop while on polymyxin therapy most often are mild to moderate in magnitude and reversible in nature. Strategies to minimize toxicity associated with polymyxins have evolved and include avoidance of toxic medications, careful dosing, use of critical care, therapeutic drug monitoring and development of polymyxin derivatives. However, given that polymyxin use has re-emerged in an era of increased antimicrobial resistance, the presence of other treatment modalities may be limited. Therefore, clinicians must consider overall risk to benefit ratio of continuing versus stopping polymyxin treatment and optimize minimization strategies to reduce polymyxin-induced toxicities.
Histopathological study of venous aneurysms in patients with dural arteriovenous fistulas.

OBJECT Of all intracranial dural arteriovenous fistulas (DAVFs), those with cortical venous drainage associated with cortical venous ectasia or varices are predisposed to an aggressive course and produce progressive neurological symptoms or hemorrhages. The authors undertook a histological examination of venous aneurysms and arterialized veins in the proximity of these aneurysms that had been surgically removed in patients with DAVFs. METHODS Surgical specimens were obtained in eight patients. The excised venous aneurysms and the arterialized veins in their proximity were stained using hematoxylin and eosin, van Gieson's elastic, and Masson's trichrome stain. Immunostaining was also performed for alpha smooth-muscle actin, desmin, and factor VIII antigen. Five of the patients had presented with venous hypertension, and three had intracranial hemorrhages. The arterialized vein obtained in the proximity of the venous aneurysm exhibited local irregular intimal thickening; the internal elastic lamina (IEL) was grossly preserved. All venous aneurysms in patients with venous hypertension manifested medial thickening and local intimal thickening with loss of IEL; the thickness of the wall was relatively uniform. In contrast, the wall thickness of venous aneurysms in patients with hemorrhage was extremely irregular and there was no clear delineation between the media and the intima. In media with complete disappearance of IEL, there was scant muscle tissue. CONCLUSIONS Degenerative changes in venous aneurysms in patients with hemorrhage were much greater than in patients with venous hypertension, possibly because hemorrhages result from a more complicated interplay of anatomical, hemodynamic, and degenerative factors.