A systematic review of qualitative studies: patients' experiences of preoperative communication.
This article reports on a systematic review of qualitative studies on patients' experiences of preoperative communication with healthcare professionals. Communication is critical for providing efficient care to patients. It is especially important for patients waiting for surgery, as they experience a variety of unknowns before the procedure. Through communication with healthcare professionals, patients gain a better understanding of the surgery and the issues related to their life after the surgery. Thus, the preoperative communication between healthcare professionals and patients is a significant topic for review. Systematic review. Six electronic databases (CINAHL, Cochrane Library, Embase, Medline, PsycINFO and PUBMED) were systematically searched. Qualitative studies of patients' experiences before surgery were purposely selected for synthesis. Key themes and concepts were extracted and synthesised. Eleven studies on patients' experiences before surgery were identified. Four main themes relating to patients' experiences of preoperative communication with healthcare professionals were identified from all 11 articles. These themes were as follows: need for information, involving relatives, need for control and healthcare professionalism. Patients' experience of preoperative communication with healthcare professionals showed different needs and feelings for communication. Healthcare professionals need to have adequate knowledge, skills and positive attitudes to help patients through the journey of this critical life event. Patients' sensitivity and their different needs for communication may contribute to future advances in the training of healthcare professionals with regard to their communication knowledge and skills. They may also affect the allocation of resources for patients waiting for surgery and educating related professionals about their knowledge and skills of communication and their attitudes. Adequate space for meeting simultaneously with patients and their relatives and extra human resources and tools for the assessment of individuals' need for communication are also required.


The phosphatidylinositol 4-phosphate 5-kinase family.
The existence of a PIP5K family of enzymes has been suggested by Western blotting and purification of numerous PIP5Ks from various tissues and cell types. The erythrocyte has at least two PIP5Ks, named PIP5KI and PIP5KII, while the brain appears to have even more isoforms. The cloning of the first PIP5K, the PIP5KII alpha, is just the beginning of the molecular classification of this protein family. The PIP5KII alpha sequence has shown that these enzymes lack obvious homology to protein, sugar and other lipid kinases. The identification of two S. cerevisiae homologues, Mss4p and Fab1p, confirms that this family of kinases is widely distributed in eukaryotes. Not surprisingly, cloning experiments have identified additional isoforms. By cloning additional isoforms, insights into the structure and functions of this family of enzymes will be gained. One reason for a large family of PIP5Ks is that many forms of regulation and cellular functions have been ascribed to PIP5Ks, as summarized in Figure 10. Some of these functional links result from PtdIns[4,5]P2 being required for a given process, but the direct involvement of specific PIP5Ks is not well defined. Which PIP5K isoforms are regulated by a specific mechanism or are involved in a cellular process often is not clear. For example, which PIP5Ks produce PtdIns[4,5]P2 that is hydrolyzed by PLC or phosphorylated by the PI 3-kinase is not known. A few exceptions are PIP5KII not being able to phosphorylate PtdIns[4,5]P2 in native membranes, and PIP5KIs being stimulated by PtdA, required for secretion, and possibly regulated by G proteins of the Rho subfamily. The multiplicity of regulation and functions of each PIP5K isoform remains to be elucidated. Another factor governing the number of isoforms may be presence of multiple pools of polyphosphoinositides and the localizing of PIP5K function within cells. The polyphosphoinositides appear to be compartmentalized within cells and each pool appears to be sensitive to specific signals. These polyphosphoinositide pools may include those in the plasma membrane that are used by PLC, nuclear pools that appear to turn over separately from cytoplasmic pools and a small pool at sites of vesicle fusion with the plasma membrane. Each pool may be controlled by a specific PIP5K isoform. This would explain the diversity of PIP5K cellular roles. Another possibility is that the PIP5Ks are localized to certain areas of the cell by being part of a protein or proteolipid complex. Furthermore, the presence of PITP or PLC in the complex would potentially impart specificity and speed on the use of PtdIns[4]P and PtdIns[4,5]P2 because these lipids could be channeled quickly from one enzyme to the next. The concept of localized complexes containing particular PIP5K isoforms that control the composition of different polyphosphoinositide pools will likely be important as the family of PIP5K isoforms grows.


Perception and action in hemispatial neglect.
Hemispatial neglect is a neurological disorder which entails a spatial bias that penalizes events occurring in the hemispace contralateral to a brain lesion. Mechanisms operating upon various stages ranging from perception to action have been invoked to explain neglect. The present study explores the contribution of a defective programming of arm movements towards the neglected hemispace to neglect behaviour. Two reaction time tasks -- a "perceptual" task and a "motor" task -- were performed by right brain-damaged (RBD) patients with left hemispatial neglect, RBD patients without signs of neglect and control subjects. The perceptual task consisted of lateralized visual stimuli and central motor responses, whereas the motor task consisted of visual stimuli presented on the vertical midline and hand responses to be produced in either hemispace. Neglect patients showed a rightward bias on the perceptual task, but only two RBD patients (showing no signs of severe neglect) were consistently slowed in producing leftward motor responses. Different reference frames may thus be used in perceptual tasks and tasks involving arm movements. We conclude that hemispatial neglect commonly results from attentional impairments operating upon a visual perceptual frame of reference; additional deficits appear to be necessary to produce a directional motor disorder.


Realizing Cross-linking-free Acrylic Pressure-Sensitive Adhesives with Intensive Chain Entanglement through Visible-Light-Mediated Photoiniferter-Reversible Addition-Fragmentation Chain-Transfer Polymerization.
A versatile and simplified synthesis scheme for intensively entangled acrylic pressure-sensitive adhesives (PSAs) was developed in this study by leveraging visible-light-driven controlled radical polymerization (photoiniferter/reversible addition-fragmentation chain-transfer polymerization) of acrylic copolymers under a controlled manner; the approach was differentiated by a single factor; molecular weight (Mw up to 2.8 MDa) with identical compositions. By manipulating Mw up to ultra-high ranges, PSAs with diversified viscoelastic properties were prepared and then assessed with a focus on realizing PSAs with a maximized degree of entanglement per chain through domination of high Mw contents, to help achieve excellent cohesiveness without a reinforcing cross-linking network. Moreover, fully linear solvent-soluble poly(acrylate)s were synthesized to facilitate reprocessing and reuse, highlighting the sustainability of the devised method and, consequently, its potential to be applied for effectively reducing industrial or daily waste.


Exophagy of annexin A2 via RAB11, RAB8A and RAB27A in IFN-γ-stimulated lung epithelial cells.
Annexin A2 (ANXA2), a phospholipid-binding protein, has multiple biological functions depending on its cellular localization. We previously demonstrated that IFN-γ-triggered ANXA2 secretion is associated with exosomal release. Here, we show that IFN-γ-induced autophagy is essential for the extracellular secretion of ANXA2 in lung epithelial cells. We observed colocalization of ANXA2-containing autophagosomes with multivesicular bodies (MVBs) after IFN-γ stimulation, followed by exosomal release. IFN-γ-induced exophagic release of ANXA2 could not be observed in ATG5-silenced or mutant RAB11-expressing cells. Furthermore, knockdown of RAB8A and RAB27A, but not RAB27B, reduced IFN-γ-triggered ANXA2 secretion. Surface translocation of ANXA2 enhanced efferocytosis by epithelial cells, and inhibition of different exophagic steps, including autophagosome formation, fusion of autophagosomes with MVBs, and fusion of amphisomes with plasma membrane, reduced ANXA2-mediated efferocytosis. Our data reveal a novel route of IFN-γ-induced exophagy of ANXA2.


The millennium Cohort Study: a 21-year prospective cohort study of 140,000 military personnel.
Does military service, in particular operational deployment, result in a higher risk of chronic illness among military personnel and veterans? The Millennium Cohort Study, the largest Department of Defense prospective cohort study ever conducted, will attempt to answer this question. The probability-based sample of 140,000 military personnel will be surveyed every 3 years during a 21-year period. The first questionnaire, scheduled for release in summer 2001, will be sent to 30,000 veterans who have been deployed to southwest Asia, Bosnia, or Kosovo since August 1997 and 70,000 veterans who have not been deployed to these conflict areas. Twenty thousand new participants will be added to the group in each of the years 2004 and 2007 to complete the study population of 140,000. The participants will have the option of completing the study questionnaire either on the paper copy received in the mail or through the World Wide Web-based version, which is available at www.MillenniumCohort.org. This will be one of the first prospective studies ever to offer such an option. The initial survey instrument will collect data regarding demographic characteristics, self-reported medical conditions and symptoms, and health-related behaviors. Validated instruments will be incorporated to capture self-assessed physical and mental functional status (Short Form for Veterans), psychosocial assessment (Patient Health Questionnaire), and post-traumatic stress disorder (Patient Checklist-17). Information obtained from the survey responses will be linked with other military databases, including data on deployment, occupation, vaccinations, health care utilization, and disability. In addition to revealing changes in veterans' health status over time, the Millennium Cohort Study will serve as a data repository, providing a solid foundation upon which additional epidemiological studies may be constructed.


Adventitial cystic disease of the lesser saphenous vein.
Adventitial cystic disease or degeneration of the blood vessel wall is an unusual form of peripheral vascular disease that occurs almost exclusively in the popliteal artery and accounts for an estimated one in 1200 cases of claudication. The cause of adventitial cystic disease is unknown, but it has been attributed to repeated trauma, an ectopic ganglion, or primary dysplasia of the vascular connective tissue. We describe an unusual case of adventitial cystic disease of the lesser saphenous vein located adjacent to the ankle joint. Only a handful of cases of venous adventitial cystic disease have been reported in the English literature, and, to our knowledge, none involved the lesser saphenous vein.


Pivotal Roles of Ginsenoside Rg3 in Tumor Apoptosis Through Regulation of Reactive Oxygen Species.
Elevated production of reactive oxygen species (ROS) is observed in various cancer types and pathophysiological conditions. In cancer cells, ROS induce cell proliferation, genetic instability, and a malignant phenotype. Ginsenoside Rg3 is the main pharmacologically active component in ginseng and has been reported to have an antioxidant effect. To overcome lung cancer by regulating the ROS level, we investigated the antitumor effect and mechanism of Rg3 and its antioxidative property on Lewis lung carcinoma (LLC) cells. Inhibition of ROS was suppressed in LLC cells by Rg3 treatment, and these cells were used to investigate the antioxidant, antiproliferative, and antitumor effects in LLC cells. ROS production was increased in cells grown in serum-containing media (conditioned media) compared to those grown in serum-free media. The high level of ROS induced LLC cell proliferation, but treatment with Rg3 (200 ng/ml) resulted in reduction of ROS, leading to inhibition of cell proliferation. Treatment with Rg3 significantly reduced cyclin and cyclin-dependent kinase expression in LLC cells. Additionally, Rg3 treatment significantly suppressed activation of mitogen-activated protein kinases and induced LLC cell apoptosis through activation of pro-apoptotic proteins and suppression of anti-apoptotic proteins. Taken together, these findings demonstrate the role of Rg3 in reduction of the intracellular ROS level, attenuation of proliferation via augmentation of cell cycle- and cell proliferation-associated proteins, and activation of apoptosis through regulation of apoptosis-associated proteins in LLC. These findings suggest that Rg3 could be used as a therapeutic agent in lung cancer.


[Current Issues in Photosafety Evaluation].
Phototoxicity is a toxic response elicited by topically applied or systemically administered photoreactive chemicals after exposure to light and can be broadly categorized into photoirritation, photoallergy, photogenotoxicity, and photocarcinogenicity. The need in the 21st century for accurate evaluation of photosafety has led to the publication of a number of guidelines from government agencies in Europe and the U.S.A. as well as the Organisation for Economic Co-operation and Development (OECD). In this review, we first discuss the mechanisms of phototoxicity and how they can be evaluated. We then discuss the state of the art and challenges now faced in photosafety evaluation of pharmaceuticals and cosmetics. Additionally, we describe the latest developments in OECD test guidelines (TG) for assessing photosafety, including revisions to the in vitro 3T3 neutral red uptake (NRU) phototoxicity test (TG 432) and the newly adopted reactive oxigen species (ROS) assay (TG 495). We will emphasize the importance of selecting the most appropriate means of evaluation with reference to the latest guidelines and other legal criteria for conducting photosafety evaluation.


The effect of the macrophage migration inhibitory factor (MIF) on excisional wound healing in vivo.
Background: The macrophage migration inhibitory factor (MIF) has been determined as a cytokine exerting a multitude of effects in inflammation and angiogenesis. Earlier studies have indicated that MIF may also be involved in wound healing and flap surgery. Methods: We investigated the effect of MIF in an excisional wound model in wildtype, Mif-/- and recombinant MIF treated mice. Wound closure rates as well as the macrophage marker Mac-3, the pro-inflammatory cytokine tumor necrosis factor α (TNFα) and the pro-angiogenic factor von Willebrand factor (vWF) were measured. Finally, we used a flap model in Mif-/- and WT mice with an established perfusion gradient to identify MIF's contribution in flap perfusion. Results: In the excision wound model, we found reduced wound healing after MIF injection, whereas Mif deletion improved wound healing. Furthermore, a reduced expression of Mac-3, TNFα and vWF in Mif-/- mice was seen when compared to WT mice. In the flap model, Mif-/- knockout mice showed mitigated flap perfusion with lower hemoglobin content and oxygen saturation as measured by O2C measurements when compared to WT mice. Conclusions: Our data suggest an inhibiting effect of MIF in wound healing with increased inflammation and perfusion. In flaps, by contrast, MIF may contribute to flap vascularization.


Associations of Macro- and Microvascular Endothelial Dysfunction With Subclinical Ventricular Dysfunction in End-Stage Renal Disease.
Patients with end-stage renal disease (ESRD) suffer high rates of heart failure and cardiovascular mortality, and we lack a thorough understanding of what, if any, modifiable factors contribute to cardiac dysfunction in these high-risk patients. To evaluate endothelial function as a potentially modifiable cause of cardiac dysfunction in ESRD, we investigated cross-sectional associations of macro- and microvascular dysfunction with left and right ventricular dysfunction in a well-controlled ESRD cohort. We performed comprehensive echocardiography, including tissue Doppler imaging and speckle-tracking echocardiography of the left and right ventricle, in 149 ESRD patients enrolled in an ongoing prospective, observational study. Of these participants, 123 also underwent endothelium-dependent flow-mediated dilation of the brachial artery (macrovascular function). Microvascular function was measured as the velocity time integral of hyperemic blood flow after cuff deflation. Impaired flow-mediated dilation was associated with higher left ventricular mass, independently of age and blood pressure: per 2-fold lower flow-mediated dilation, left ventricular mass was 4.1% higher (95% confidence interval, 0.49-7.7; P=0.03). After adjustment for demographics, blood pressure, comorbidities, and medications, a 2-fold lower velocity time integral was associated with 9.5% higher E/e' ratio (95% confidence interval, 1.0-16; P=0.03) and 6.7% lower absolute right ventricular longitudinal strain (95% confidence interval, 2.0-12; P=0.003). Endothelial dysfunction is a major correlate of cardiac dysfunction in ESRD, particularly diastolic and right ventricular dysfunction, in patients whose volume status is well controlled. Future investigations are needed to determine whether therapies targeting the vascular endothelium could improve cardiac outcomes in ESRD.


A new phyllocarid (Crustacea: Malacostraca) from the Silurian Fossil-Lagerstätte of Herefordshire, UK.
A new three-dimensionally preserved arthropod, Cinerocaris magnifica, from the Wenlock Series (Silurian) of Herefordshire, UK, is described and assigned to the Phyllocarida (Crustacea). The description and reconstruction are based on specimens that have been serially ground, reconstructed by computer and rendered in three dimensions as coloured virtual models. Cinerocaris magnifica displayed the tagmosis characteristic of phyllocarids, with eight thoracic and seven abdominal somites, terminating in a telson with furca. The remarkable preservation of the appendages makes this the earliest completely known malacostracan crustacean. Two pairs of antennae (the first with two flagella) were followed by a mandible and first maxilla, each with a slender palp-like ramus. The second maxilla consisted of a limb stem with endites and an endopod that tapered distally. There was no exopod. The thoracopods comprised a limb stem with six or seven endites, an arrangement previously known only in entomostracans, and an endopod with about five endites. Flap-like outer rami correspond to an exopod and epipods. The pleopods bore two long slender oar-blade-like rami. Cladistic analysis places C. magnifica as a plesion within the Echinocaridina. It provides critical evidence of the limb morphology of an early malacostracan, which will be important in understanding crustacean evolution.


Swimming against the tide: investigations of the C-bouton synapse.
C-boutons are important cholinergic modulatory loci for state-dependent alterations in motoneuron firing rate. m2 receptors are concentrated postsynaptic to C-boutons, and m2 receptor activation increases motoneuron excitability by reducing the action potential afterhyperpolarization. Here, using an intensive review of the current literature as well as data from our laboratory, we illustrate that C-bouton postsynaptic sites comprise a unique structural/functional domain containing appropriate cellular machinery (a "signaling ensemble") for cholinergic regulation of outward K(+) currents. Moreover, synaptic reorganization at these critical sites has been observed in a variety of pathologic states. Yet despite recent advances, there are still great challenges for understanding the role of C-bouton regulation and dysregulation in human health and disease. The development of new therapeutic interventions for devastating neurological conditions will rely on a complete understanding of the molecular mechanisms that underlie these complex synapses. Therefore, to close this review, we propose a comprehensive hypothetical mechanism for the cholinergic modification of α-MN excitability at C-bouton synapses, based on findings in several well-characterized neuronal systems.


miRNA-125b regulates apoptosis of human non-small cell lung cancer via the PI3K/Akt/GSK3β signaling pathway.
The present investigation demonstrated that regulation of microRNA (miR)-125b affected the apoptosis of human non-small cell lung cancer (NSCLC) through targeting of the PI3K/Akt and Wnt/β-catenin signaling pathways. The expression of miR-125b was assessed in patients with NSCLC, which demonstrated that miR-125b expression in NSCLC tissue was higher than that in para-carcinoma tissue. Furthermore, survival analysis of patients with NSCLC over 3 years indicated that the overall survival (OS) and disease-free survival (DFS) rates of patients with low miR-125b expression were higher than those of patients with high miR-125b expression. Proliferation and apoptosis assays were subsequently conducted in the human NSCLC cell line A549 using MTT assay and Annexin V-FITC/PI kits, respectively. Caspase-3 activity ELISA and western blot analysis were also used to assess caspase-3 activity and the protein expression of Bax, Akt, phosphorylated (p)-Akt, p-GSK3β, Wnt and β-catenin. It was observed that downregulation of miR-125b inhibited the proliferation and induced the apoptosis of A549 cells. Downregulation of miR-125b also suppressed the protein expression of p-Akt, Wnt and β-catenin, and increased caspase-3 activity and Bax protein expression in A549 cells. In addition, downregulation of miR-125b combined with the PI3K inhibitor LY294002 enhanced cell growth inhibition, suppression of p-GSK3β, Wnt and β-catenin protein expression and promotion of caspase-3 activity in A549 cells. These results revealed that the downregulation of miR-125b regulates apoptosis in human NSCLC through the suppression of the PI3K/Akt/GSK3β and Wnt/β-catenin signaling pathways.


[Correlation between the prick test and specific IgE against allergens of house dust and Dermatophagoides sp].
Of the techniques which are usually used for the in vitro etiologic diagnosis of determined allergic processes, it is the RAST technique which is most widely used for determining specific antibodies of the IgE class. On the other hand, also of interest is the quantification of total IgE in these patients. We have studied 80 allergic and non allergic patients in order to evaluate the possible correlation between the Prick and the RAST tests applied to different allergens such house dust. Dermatophagoides pteronyssinus and Dermatophagoides farinae. The patients were distributed in four groups in relation to the clinical history and serum levels of total IgE, as follows: Group I: Patients with positive clinical history and increases levels of total IgE. Group II: patients with positive history and normal values of total IgE. Group III: patients with negative history and increased levels of serum IgE, and Group IV with non atopic subjects with normal values of IgE. The results show a high correlation between both tests for house dust mite allergens in the group I. The relation to inferior in the group II. As far as house dust is concerned, there is no correlation between the cutaneous test in the RAST test even in the group with positive clinical history. The data observed with house dust mites suggest a relation between the clinical history and the cutaneous test and also between the RAST and the levels of total serum IgE. These relations are not fund with house dust. It is discussed the validity and applications of both tests to the diagnosis of immediate hypersensitivity reactions to house dust mites and house dust.


Potential application of fish scales as feedstock in thermochemical processes for the clean energy generation.
The replacement of fossil fuels by renewable sources has been discussed globally, because fossil fuels account for a large portion of the pollutant emissions into the atmosphere. Several cities along the Brazilian coast produce a variety of fish types, generating a large amount of waste, including viscera and fish scales, which are already used in several industrial processes. However, these cities still face a large environmental problem, i.e., residue disposal from commercial establishments, e.g., fishmongers, which are often discarded in a disordered and/or unplanned manner in inappropriate places. Within this scenario, the energy utilization of an animal biomass supplied by a fishery in the city of São Luís was investigated, submitting samples to combustion (synthetic air) and pyrolysis (100% N2) processes for the bioenergy generation. Physicochemical properties from fish scales were evaluated by proximate and ultimate analyzes, scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-Ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and inductively coupled plasma - optical emission spectroscopy (ICP-OES). The thermal behavior of samples was evaluated by thermogravimetry/derivative thermogravimetry (TG/DTG), differential thermal analysis (DTA) and calorimetry (HHV/LHV). It was verified that the fish scales have carbon and oxygen the major elements, and insignificant amounts of sulfur and heavy metals (lead, copper, chromium, lithium, zinc). This material also presented a large amorphous region (89%), in addition to the presence of collagen fibers and hydroxyapatite crystals. The thermal and physicochemical characteristics of this material were evaluated and compare it to other biomasses already in use, predicting its use for the bioenergy generation.


Thyroid hormone-dependent adult pigment cell lineage and pattern in zebrafish.
Pigment patterns are useful for elucidating fundamental mechanisms of pattern formation and how these mechanisms evolve. In zebrafish, several pigment cell classes interact to generate stripes, yet the developmental requirements and origins of these cells remain poorly understood. Using zebrafish and a related species, we identified roles for thyroid hormone (TH) in pigment cell development and patterning, and in postembryonic development more generally. We show that adult pigment cells arise from distinct lineages having distinct requirements for TH and that differential TH dependence can evolve within lineages. Our findings demonstrate critical functions for TH in determining pigment pattern phenotype and highlight the potential for evolutionary diversification at the intersection of developmental and endocrine mechanisms.


History, rare, and multiple events of mechanical unfolding of repeat proteins.
Mechanical unfolding of proteins consisting of repeat domains is an excellent tool to obtain large statistics. Force spectroscopy experiments using atomic force microscopy on proteins presenting multiple domains have revealed that unfolding forces depend on the number of folded domains (history) and have reported intermediate states and rare events. However, the common use of unspecific attachment approaches to pull the protein of interest holds important limitations to study unfolding history and may lead to discarding rare and multiple probing events due to the presence of unspecific adhesion and uncertainty on the pulling site. Site-specific methods that have recently emerged minimize this uncertainty and would be excellent tools to probe unfolding history and rare events. However, detailed characterization of these approaches is required to identify their advantages and limitations. Here, we characterize a site-specific binding approach based on the ultrastable complex dockerin/cohesin III revealing its advantages and limitations to assess the unfolding history and to investigate rare and multiple events during the unfolding of repeated domains. We show that this approach is more robust, reproducible, and provides larger statistics than conventional unspecific methods. We show that the method is optimal to reveal the history of unfolding from the very first domain and to detect rare events, while being more limited to assess intermediate states. Finally, we quantify the forces required to unfold two molecules pulled in parallel, difficult when using unspecific approaches. The proposed method represents a step forward toward more reproducible measurements to probe protein unfolding history and opens the door to systematic probing of rare and multiple molecule unfolding mechanisms.


[Thoracoscopy in nonspecific spontaneous and iatrogenic pneumothorax].
Thoracoscopy was used in 92 patients. The etiology of pneumothorax was established in 76 patients. In most of them the treatment was effective. Suture of the pleura and lung defect, pleurodesis, pleurectomy, coagulation of tissues were performed under the control of thoracoscope. Thoracoscopy allowed to avoid extensive thoracotomy, to shorten the period of treatment at the hospital.


Searching the expressive face: evidence for both the right hemisphere and valence-specific hypotheses.
Quick and accurate judgments of emotional expressivity and attractiveness facilitate social interactions. Eye tracking was used to examine left/right asymmetries across 2 studies. Fixations to each hemiface, and to the eyes and mouth, when judging attractiveness and emotional expressivity were examined. Overall, more fixations occurred on the left hemiface (from the viewer's point of view), even when mirror-reversed, supporting the suggestion that we intuitively know the left hemiface is more expressive. The right side of the mouth was fixated more when judging happiness, whereas the left eye was fixated more for sadness and the left mouth when rating emotional expressivity. The present findings support the notion that the right hemisphere and valence-specific hypotheses are not mutually exclusive. The right hemisphere hypothesis is supported when assessing global facial qualities (i.e., hemiface); however, hemispheric processing differences emerge when exploring the eyes and mouth. The current findings highlight the importance of not only considering how the face is examined more generally, but of also exploring smaller regions of interest to investigate lateral biases. Future research should therefore include analyses of fixations to the hemifaces, as well as to these smaller regions of interest.


Aberrant nestin expression during ethylnitrosourea-(ENU)-induced neurocarcinogenesis.
Nestin is a unique intermediate filament protein. While it is robustly expressed in developing brain, postnatal expression is limited to the brain's subventricular zone (SVZ) and endothelial cells. Reexpression occurs, however, under several pathological conditions, including injury and neoplasia. We hypothesized that nestin would be a sensitive marker of early neoplasia after transplacental exposure of rats to ethylnitrosourea (ENU). Rats of various ages were administered bromodeoxyuridine (BudR) before sacrifice, and brain sections were examined for proliferative cells and several immunohistochemical markers, including nestin. Additional rats were examined after a stab wound injury to assess the expression of two of these markers, GFAP and nestin, in reactive astrocytes. All ENU-induced brain tumors (n = 9) were classified as gliomas (astrocytomas or oligoastrocytomas) based on their histology and immunophenotype. Nestin expression was noted in all tumors examined and was present in tumor cells as well as endothelial cells. During tumor development, we consistently noted nestin-expressing cells bearing multiple processes distributed throughout brain parenchyma. Both single cells and multiple cell clusters were observed as early as postnatal day 30 in all ENU-exposed brains examined (n = 11). Such distinctive nestin-expressing cells were not seen in nestin-stained control brains or ENU-exposed brains stained for GFAP or vimentin, nor was such a cell seen in a stab wound model used to assess reactive astrocytosis. While the number of these clusters was highly variable among rats, their size increased between 30 and 90 days. The data suggest that these nestin-expressing cells represent an early stage of the neoplastic process. It remains to be determined whether these cells become apparent at 30 days of age due to "dedifferentiation" of a local resident astrocyte or astrocyte precursor cell or migration of a relatively undifferentiated precursor/stem cell from the SVZ.


Mother's educational level and fetal growth: the genesis of health inequalities.
Women of low socio-economic status (SES) give birth to lighter babies. It is unknown from which moment during pregnancy socio-economic differences in fetal weight can be observed, whether low SES equally affects different fetal-growth components, or what the effect of low SES is after taking into account mediating factors. In 3545 pregnant women participating in the Generation R Study, we studied the association of maternal educational level (high, mid-high, mid-low and low) as a measure of SES with fetal weight, head circumference, abdominal circumference and femur length. We did this before and after adjusting for potential mediators, including maternal height, pre-pregnancy body mass index and smoking. In fetuses of low-educated women relative to those of high-educated women, fetal growth was slower, leading to a lower fetal weight that was observable from late pregnancy onwards. In these fetuses, growth of the head [-0.16 mm/week; 95% confidence interval (CI): -0.25 to -0.07; P = 0.0004], abdomen (-0.10 mm/week; 95% CI: -0.21 to 0.01; P = 0.08) and femur (-0.03 mm/week; 95% CI: -0.05 to -0.006; P = 0.01) were all slower; from mid-pregnancy onwards, head circumference was smaller, and from late pregnancy onwards, femur length was also smaller. The negative effect of low education was greatest for head circumference (difference in standard deviation score in late pregnancy: -0.26; 95% CI: -0.36 to -0.15; P < 0.0001). This effect persevered even after adjustment for the potential mediators (adjusted difference: -0.14; 95% CI: -0.25 to -0.03; P = 0.01). Low maternal education is associated with a slower fetal growth and this effect appears stronger for growth of the head than for other body parts.


[Role of membrane structure in the formation of the myofibrillar system in myogenesis].
The leading role of membranes in the formation of the myofibrillar system at different stages of chick embryo development (on the 8th, 12th, 15th day) was considered. At the early stages the myofibrillar assembly depends mainly on the plasma membrane (myofibrils are located beneath the sarcolemma) and later on it depends on the developing sarcoplasmic reticulum and T-system. It was shown that transverse tubules invaginating from the plasma membrane are the framework for the forming myofibrillar system, and thin filaments are attached to the transverse tubules at the sites of future Z-lines. These results support the idea that Z-lines originate from the membrane. Destruction of the membrane elements provokes disorganization of myofibrillar contractile material.


Factors affecting career choice among the next generation of academic vascular surgeons.
Few studies have examined factors that influence an individual's decision to enter an academic medical career after residency training. We sought to evaluate whether sex, ethnicity, child care issues, and debt burden influenced residents' choice for a career in academic vascular surgery. A 39-item Web survey, designed to elucidate which factors motivated residents to seek a career in academic vascular surgery, was sent to 295 vascular surgery residents currently enrolled in Accreditation Council on Graduate Medical Education-accredited training programs. A total of 128 responses (43%) were received. Of these, 53% of respondents were white and 47% were nonwhite and 34 (27%) were women and 94 (73%) were men. Fifty-seven percent of minorities anticipate a career in academic vascular surgery. There were no statistical differences between sex and ethnicity for factors influencing career choice, including training paradigm, presence of a life partner or dependents, mentorship role, participation in research, service, and teaching, anticipated salary, and debt burden (P > .05). Seventy-seven percent of respondents carry significant debt; of those with debt, 81% owe >$100,000 and 40% owe >$200,000. Seventy-three percent of 0+5 trainees anticipated choosing an academic practice compared with 42% of 5+2 trainees (P < .01). Respondents planning an academic career cited procedural variation, breadth and depth of practice/tertiary referral experience, and research opportunities as the most important drivers of career choice. Income potential, strength of the job market, and child care needs were deemed less important. This study shows that academic vascular surgery is a popular career option for current vascular surgery trainees, especially those in 0+5 programs. Choosing a career in academic vascular surgery appears not to be influenced by sex, ethnicity, child care concerns, salary expectations, or debt burden, even though most trainees carry enormous debt. The data imply future academic vascular surgeons will likely have greater gender and ethnic variability than is currently seen.


Prevalence of Toxoplasma gondii infection in wild birds in Durango, Mexico.
There is a lack of information concerning the prevalence of Toxoplasma gondii infection in wild birds in Mexico. In the present study, serum samples and tissues from 653 birds from Durango State, Mexico, were evaluated for T. gondii infection. Antibodies to T. gondii (modified agglutination test, titer 1∶25 or higher) were found in 17 (2.6%) of the 653 birds, including 1 of 2 curve-billed thrashers (Toxostoma curvirostre), 2 (1 Anas platyrhynchos, 1 Anas diazi) of 4 ducks, 1 of 2 eagles (Aquila sp.), 5 (27.8%) of 18 great-tailed grackles (Quiscalus mexicanus), 7 (1.3%) of 521 rock pigeons (Columba livia), and 1 (14.3%) of 7 quail (Coturnix coturnix). The seroprevalence of T. gondii infection in birds captured in a park outside the city zoo (11.6%, 8/69) was significantly higher than that found in birds from other regions (1.5%, 9/584, OR = 8.38; 95% CI: 2.82-24.77; P = 0.0001). Brains and hearts of 23 birds (17 seropositive, 6 seronegative) were bioassayed in mice for the isolation of T. gondii . Viable T. gondii was isolated from 1 of 7 seropositive pigeons. The DNA obtained from the T. gondii isolate from the pigeon was genotyped using the PCR-RFLP typing using 11 markers (B1, SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico) and revealed an atypical genotype. This is the first report of T. gondii infection in great-tailed grackles, the Mexican duck, and curved-billed thrashers and the first survey of wild birds in Mexico.


[General and local antibiotic treatment with ceftriaxone of suppurative-septic diseases and complications].
A third-generation cephalosporin, Ceftriaxone, was used in intensive care of patients subjected to elective and urgent surgery in the Regional Clinical Hospital, St. Petersburg. A total of 105 patients were divided in 4 groups: 1) a course of ceftriaxone in combination with aminoglycosides started before the intervention; 2) the same, with the disease course complicated by peritonitis; 3) patients with neurosurgical diseases and brain injuries complicated by secondary meningoencephalitis; and 4) abdominal surgical patients in whom the severity of illness was determined by the abdominal process of different localization. The treatment included general and local use of ceftriaxone under ultrasonic control. The results indicate that ceftriaxone is a broad-spectrum drug effective in the treatment of nosocomial infections and neuroinfections; it can be applied locally and is economic.


Life-cycle analysis of environmental loads from household septic systems in Japan focusing on effluent water discharge.
Various types of small-scale wastewater treatment systems are widely used in rural areas, and life-cycle assessment (LCA) should be performed to evaluate their environmental performance. In this study, septic systems were first classified into five categories based on their wastewater treatment performance. Effluent samples from actual systems were collected, and their water qualities were determined. A model to evaluate the environmental load from the septic systems using LCA methods was then established. The water-quality values obtained were input to the model, and the life-cycle environmental costs of the classified septic systems were calculated. The mean environmental load of the effluent during the operation stage was 37.6%, confirming that evaluation of an effluent discharge inventory using LCA, inspection, and water-quality monitoring to improve operations is critical for reducing the environmental load. The operation stage accounts for over 99% of the involved eutrophication, biological toxicity, and toxic chemicals, which are strongly related to the quality of the effluent. Evaluation of the effluent discharge inventory using LCA is of great significance, even for small-scale wastewater treatment systems. The set of procedures developed in this study can be used to calculate comprehensive environmental impacts at wastewater treatment plants.


Microbial Consortium Associated with the Antarctic Marine Ciliate Euplotes focardii: An Investigation from Genomic Sequences.
We report the characterization of the bacterial consortium associated to Euplotes focardii, a strictly psychrophilic marine ciliate that was maintained in laboratory cultures at 4 °C after its first isolation from Terra Nova Bay, in Antarctica. By Illumina genome analyser, we obtained 11,179 contigs of potential prokaryotic origin and classified them according to the NCBI's prokaryotic attributes table. The majority of these sequences correspond to either Bacteroidetes (16 %) or Proteobacteria (78 %). The latter were dominated by gamma- (39 %, including sequences related to the pathogenic genus Francisella), and alpha-proteobacterial (30 %) sequences. Analysis of the Pfam domain family and Gene Ontology term variation revealed that the most frequent terms that appear unique to this consortium correspond to proteins involved in "transmembrane transporter activity" and "oxidoreductase activity". Furthermore, we identified genes that encode for enzymes involved in the catabolism of complex substance for energy reserves. We also characterized members of the transposase and integrase superfamilies, whose role in bacterial evolution is well documented, as well as putative antifreeze proteins. Antibiotic treatments of E. focardii cultures delayed the cell division of the ciliate. To conclude, our results indicate that this consortium is largely represented by bacteria derived from the original Antarctic sample and may contribute to the survival of E. focardii in laboratory condition. Furthermore, our results suggest that these bacteria may have a more general role in E. focardii survival in its natural cold and oxidative environment.


All-biomaterial laser using vitamin and biopolymers.
Lasers based on biomaterials known as Generally-Recognized-As-Safe (GRAS) substances approved by the U.S. Food and Drug Administration (FDA) are demonstrated. Vitamin B2-doped microdroplet lasers are generated and trapped on a super-hydrophobic poly-L-lactic acid substrate. The spheres support whispering gallery mode lasing at optical pump energies as low as 15 nJ per pulse (≈1 kW/mm2).


Predictors and outcome of readmission after laparoscopic intestinal surgery.
Previous studies have failed to identify predictors of early readmission after major intestinal operations. The objectives of this study were to determine readmission rates, outcomes, and predictors of readmission for patients undergoing laparoscopic colon and rectal operations. Patients readmitted (PR) to the hospital within 30 days of discharge after laparoscopic colon and rectal operations were identified from a prospectively maintained database. The PR group was compared with patients that were not readmitted (NR). Outcomes and variables related to readmission were evaluated. There were 820 consecutive elective laparoscopic colon and rectal operations performed over a 5-year period, with adequate follow-up data for 787 cases. Seventy-nine (10%) patients were readmitted. There was no difference in the age, sex, surgeon, or type of operation between the PR and NR groups. The most common causes for readmission were bowel obstruction (19%), ileus (18%), intra-abdominal abscess (14%), and anastomotic leak (9%). Overall mean (median) length of stay (LOS) for the index admission was 3.7 +/- 4.3 (3.0) days. Patients in the PR group had a trend toward a longer index admission LOS than the NR group (5.4 +/- 8.8 [3.0] versus 3.5 +/- 3.3 [3.0], p = 0.068). Univariate analysis demonstrated that patients with inflammatory bowel disease, pulmonary comorbidities, and steroid use were more likely to be readmitted. Multivariate analysis confirmed that inflammatory bowel disease and pulmonary comorbidity are independent risk factors for readmission. Early readmission after laparoscopic colon and rectal operations is not associated with early discharge. Identification of specific patient characteristics indicating risk for early readmission may allow for selective changes in perioperative care or discharge criteria to avoid unexpected readmission. An erratum to this article can be found at


Effect of spermidine on misfolding and interactions of alpha-synuclein.
Alpha-synuclein (α-Syn) is a 140 aa presynaptic protein which belongs to a group of natively unfolded proteins that are unstructured in aqueous solutions. The aggregation rate of α-Syn is accelerated in the presence of physiological levels of cellular polyamines. Here we applied single molecule AFM force spectroscopy to characterize the effect of spermidine on the very first stages of α-Syn aggregation--misfolding and assembly into dimers. Two α-Syn variants, the wild-type (WT) protein and A30P, were studied. The two protein molecules were covalently immobilized at the C-terminus, one at the AFM tip and the other on the substrate, and intermolecular interactions between the two molecules were measured by multiple approach-retraction cycles. At conditions close to physiological ones at which α-Syn misfolding is a rare event, the addition of spermidine leads to a dramatic increase in the propensity of the WT and mutant proteins to misfold. Importantly, misfolding is characterized by a set of conformations, and A30P changes the misfolding pattern as well as the strength of the intermolecular interactions. Together with the fact that spermidine facilitates late stages of α-Syn aggregation, our data demonstrate that spermidine promotes the very early stages of protein aggregation including α-Syn misfolding and dimerization. This finding suggests that increased levels of spermidine and potentially other polyamines can initiate the disease-related process of α-Syn.


Idiopathic multicentric Castleman disease with novel heterozygous Ile729Met mutation in exon 10 of familial Mediterranean fever gene.
While the aetiology of idiopathic multicentric Castleman disease (iMCD) remains unclear, the involvement of autoinflammatory mechanisms has been suggested. Herein we report a Japanese patient with iMCD with a novel heterozygous Ile729Met mutation in exon 10 of the Mediterranean fever (MEFV) gene. We performed genetic analysis via targeted next-generation sequencing analysis and Sanger sequencing and conducted molecular dynamics simulations to investigate the hydrophobic interactions around the 729th amino acid in human pyrin. In February 2011, a 59-year-old man was diagnosed with IgG4-related disease at our department based on the findings of cervical and hilar lymphadenopathies, typical lung lesions and cervical lymph node biopsy. The patient was followed up without treatment, as he was asymptomatic. However, he had been experiencing prolonged fatigue and fever with high levels of CRP since June 2017. Axillary lymph node biopsy findings led to the diagnosis of iMCD. He was successfully treated with an IL-6 inhibitor and has been in remission for 12 months. Genetic analyses for hereditary autoinflammatory disease-related genes were performed, revealing a novel heterozygous Ile729Met mutation in exon 10 of the MEFV gene. We identified that this novel mutation significantly altered the local interaction of the human pyrin B30.2 domain by molecular dynamics simulation analysis and experimentally had the potential for inflammasome activation with increased inflammatory cytokines. The abnormal function of pyrin due to a mutation in the MEFV gene in this patient may have contributed to the development of MCD by inducing IL-6 production via inflammasome signalling.


The effects of Nobiletin, Hesperetin, and Letrozole in a combination on the activity and expression of aromatase in breast cancer cells.
Nobiletin (NOB) and hesperetin (HES) are the citrus polymethoxyflavone and flavonone. Aromatase or cytochrome P450 (CYP19) enzyme is a key enzyme in estrogen biosynthesis. The objective of this study was to investigate the combinational effects of HES, NOB and letrozole (LET) as aromatase inhibitors on the activity and expression of aromatase in MCF-7 cells. In this study, aromatase enzyme activity based on the conversion of androgen substrate testosterone to 17β-Estradiol was determined. Estradiol concentrations were measured using an electrochemiluminescence immunoassay. CYP19 gene expression was determined by quantitative real-time PCR. Our findings demonstrated that none of combinations including LET+NOB, LET+HES, LET+NOB+HES, and NOB+HES had no significant effects on aromatase activity and expression. The present study showed for the first time that the combination of HES, NOB, and LET had no effects on activity and expression of aromatase in MCF-7 breast cancer cells.


Developments in ion mobility spectrometry-mass spectrometry.
Ion mobility spectrometry (IMS) has been used for over 30 years as a sensitive detector of organic compounds. The following is a brief review of IMS and its principles with an emphasis on its usage when coupled to mass spectrometry. Since its inception, IMS has been interfaced with quadrupole, time-of-flight, and Fourier-transform ion cyclotron resonance mass spectrometry. These hybrid instruments have been employed for the analysis of a variety of target analytes, including biomolecules, explosives, chemical warfare degradation products, and illicit drugs.


Preventing violence against children in schools (PVACS): protocol for a cluster randomised controlled trial of the EmpaTeach behavioural intervention in Nyarugusu refugee camp.
We aim to test the effectiveness of the EmpaTeach intervention to prevent physical violence from teachers to students in Nyarugusu Refugee Camp, Tanzania. EmpaTeach is a 10-week, 14-session, classroom management and cognitive-behavioural therapy-based intervention for groups of teachers for delivery by lay personnel in resource-constrained settings. We will conduct a two-arm cluster randomized controlled trial (RCT) with parallel assignment and an approximately 1:1 allocation ratio. All primary and secondary schools in Nyarugusu will be invited to participate. Whole schools will be stratified according to whether they are Congolese or Burundian, and primary or secondary schools, then randomised to active intervention or wait-list control conditions via a public meeting with headteachers. We will collect survey data from n = 500 teachers and at least n = 1500 students before the intervention, soon after, and at least 6 months after the end of the intervention. The primary outcome measure will be students' self-reports of experience of physical violence from school staff in the past week, measured using a modified version of the International Society for the Prevention of Child Abuse and Neglect Screening Tool-Child Institutional at the first follow-up after the intervention. Secondary outcomes include emotional violence, depressive symptoms and educational test scores. Analysis will be intention to treat, using repeat cross-sectional data from individuals. If successful, the EmpaTeach intervention would represent one of a handful of proven interventions to reduce violence from teachers to students in any setting. IRC provides an immediate platform for scale up of the intervention via its current work in more than 40 conflict-affected countries. NCT03745573 , registered November 19, 2018 at clinicaltrials.gov, https://clinicaltrials.gov/ct2/show/NCT03745573 .


Cholesterol sulfate: a naturally-occurring inhibitor of cholesterol side-chain cleavage which functions at the level of intramitochondrial cholesterol translocation.
Cholesterol sulfate is a naturally occurring compound which is widely distributed among various tissues including the adrenal cortex. When added to adrenal mitochondria from ether-stressed rats, it inhibits pregnenolone synthesis from exogenous but not endogenous cholesterol. Evidence supports a locus of action at the level of an intramitochondrial cholesterol translocation system with no effect on the side-chain cleavage enzymatic system (cytochrome P-450scc). Levels of endogenous cholesterol sulfate in the adrenal are similar to the Ki for inhibition by this compound, suggesting a possible physiological role. Moreover, quantities of cholesterol sulfate present in isolated mitochondria from ether-stressed animals are variable, and levels correlate inversely with rates of pregnenolone production by these preparations. In the presence of malate, mitochondrial cholesterol sulfate is metabolized slowly to pregnenolone sulfate, and its removal correlates with activation of cholesterol side-chain cleavage. Cholesterol sulfate levels are not regulated acutely by stress, but can be decreased significantly after several weeks of daily injection of ACTH (a model of chronic stress). Such treatments result in an increased capacity of isolated adrenal mitochondria to synthesize pregnenolone, and increased activity correlates with increased levels of circulating corticosterone. Thus, we propose that cholesterol sulfate is a new physiological regulator of steroid hormone biosynthesis which may function to regulate the magnitude of the steroidogenic response of the adrenal cortex to ACTH.


Standardization of the registration and analysis of mastication: proposal for clinical application.
The purpose of this study was to verify the inter-rater agreement level as a means of obtaining an efficiency measure of a standard mastication evaluation through video recordings. The studied population included oral breathing children and teenagers with maxillary atresia. The chewing aspects studied were mode of chewing and preferential chewing side. A white tag was placed on half the subjects' chins while the recordings were made. Two expert evaluators analyzed 54 video recordings at regular viewing speed. The lead author analyzed the same video recordings both at reduced speed and at reduced speed linked through graphical computing techniques. The analysis was conducted on chewing cycles with the viewing angle of the frontal plane. Findings indicated that when comparing the data for the three manners of watching the video recordings, the agreement level was higher for videos with the tag on the chin watched at reduced speed. It was also determined that alternating and bilateral mastication modes were prevalent (64.7%) in this sample.


Improved peri-operative outcomes with epidural analgesia in patients undergoing a pancreatectomy: a nationwide analysis.
In spite of limited evidence demonstrating a benefit, epidural analgesia (EA) is often used for patients undergoing a pancreatectomy. In the present study, the impact of epidural analgesia on post-operative outcomes after a pancreatectomy is examined. Utilizing the Nationwide Inpatient Sample, the effect of EA on peri-operative outcomes after a pancreatectomy was examined. Multivariable logistic and linear regression with propensity score matching were utilized for risk adjustment. From 2008-2011, 12,440 patients underwent a pancreatectomy. Of these, 1130 (9.1%) patients received epidural analgesia. Using univariate comparison, patients receiving EA had a significantly decreased length of stay (LOS), hospital charges and post-operative inpatient mortality. In multivariate analyses, EA was independently associated with a decreased post-operative LOS (adjusted mean difference = -1.19 days, P < 0.001), decreased hospital charges (adjusted mean difference = -$16,814, P = 0.002) and decreased post-operative inpatient mortality [adjusted odds ratio (OR) = 0.42, P < 0.001]. Using 1:1 propensity score matching, patients who received an EA (n = 1070) had significantly decreased post-operative LOS (11.0 versus 12.1 days, P = 0.011), lower hospital charges ($112,086 versus $128,939, P = 0.001) and decreased post-operative inpatient mortality (1.5% versus 3.6%, P = 0.002) compared with matched controls without EA (n = 1070). Analysis of a large hospital database reveals that EA is associated with improved peri-operative outcomes after a pancreatectomy. Additional studies are required to understand fully if this relationship is causal.


A pilot study on the effect of Catha edulis Frosk., (Celastraceae) on metabolic syndrome in WOKW rats.
This study investigated the effect of Catha edulis (khat) on some important parameters of the metabolic syndrome in Wistar Ottawa Karlsburg W (WOKW) rat. The animals were fed with the standard chow containing 5% air dried pulverized khat leaves for 14 days; followed by the standard chow for 16 days. The khat leaves were sorted into green (khat light; KL) and crimson (khat dark; KD) leaves. The control rats were fed on standard chow. Blood glucose (G), serum insulin, serum leptin and serum lipids (triglycerides, total cholesterol, HDL-, LDL-, and VLDL cholesterol) were determined. Feeding with khat leaves reduced the body weight and the triglyceride level of the animals. The effect of KD on these parameters was stronger than that of KL. KD lowered the blood glucose concentration and the leptin content whereas KL was inactive. The khat intake had no significant influence on serum insulin, total serum cholesterol, HDL-, LDL- and VLDL-cholesterol.


Determination of T cell epitopes on the S1 subunit of pertussis toxin.
To understand the immunologic characteristics of pertussis toxin molecule and to explore the possibility of developing a synthetic vaccine, T cell epitopes on the enzymatic S1 subunit of pertussis toxin were studied by measuring the proliferative response of immune murine lymph node cells and T cell lines to Ag and to synthetic peptides. The maximum in vitro T cell proliferative response was obtained by stimulating immune lymphoid cells with 20 nM of the enzymatic S1 subunit. When the T cell proliferative response of murine lymphoid cells with different MHC backgrounds was tested, only mice bearing the H-2d haplotype were high responder to the S1 subunit. To determine T cell epitopes on the S1 subunit, the proliferative response of BALB/c immune lymphoid cells to several synthetic S1 peptides was measured. Only the peptide containing amino acid residues, 65-79, was recognized by BALB/c lymphoid cells and was confirmed to contain a T cell epitope by generating S1 specific BALB/c T cell line. By using this T cell line, the response of BALB/c mice to the S1 subunit as well as to peptide 65-79 was shown to be restricted to the I-Ad sublocus of class II Ag. Finally, we showed that lymph node cells of mice immunized with peptide 65-79 respond to the native S1 subunit.


Prognostic value of the ratio between prosthesis area and indexed annulus area measured by MultiSlice-CT for transcatheter aortic valve implantation procedures.
Postprocedural aortic regurgitations following transcatheter aortic valve implantation (TAVI) procedures remain an issue. Benefit of oversizing strategies to prevent them isn't well established. We compared different level of oversizing in our cohort of consecutive patients to address if severe oversizing compared to normal sizing had an impact on post-procedural outcomes. From January 2010 to August 2013, consecutive patients were referred for TAVI with preoperative Multislice-CT (MSCT) and the procedures were achieved using Edwards Sapien(®) or Corevalve devices(®). Retrospectively, according to pre-procedural MSCT and the valve size, patients were classified into three groups: normal, moderate and severe oversizing; depending on the ratio between the prosthesis area and the annulus area indexed and measured on MSCT. Main endpoint was mid-term mortality and secondary endpoints were the Valve Academic Research Consortium (VARC-2) endpoints. Two hundred and sixty eight patients had a MSCT and underwent TAVI procedure, with mainly Corevalve(®). While all-cause and cardiovascular mortality rates were similar in all groups, post-procedural new pacemaker (PM) implantation rate was significantly higher in the severe oversizing group (P = 0.03), while we observed more in-hospital congestive heart-failure (P = 0.02) in the normal sizing group. There was a trend toward more moderate to severe aortic regurgitation (AR) in the normal sizing group (P = 0.07). Despite a higher rate of PM implantation, oversizing based on this ratio reduces aortic leak with lower rates of post-procedural complications and a similar mid-term survival.


A non-cholinergic neuronal loss in the pedunculopontine nucleus of toxin-evoked parkinsonian rats.
The pedunculopontine nucleus (PPN) controls various physiological functions, whilst being deemed a suitable target for low-frequency stimulation therapy for alleviating aspects of Parkinson's disease (PD). Previous studies showed that the PPN contains mainly cholinergic, γ-aminobutyric acid (GABA)ergic and glutamatergic neurons. Here we report on the total number of PPN neurons in laboratory rats, a species frequently used as an experimental model for simulating aspects of human PD. Moreover, the study reports that the number of PPN neurons decreases under toxic conditions that mimic in animals the core pathology seen in human PD. Immunohistochemical detection methods combined with unbiased stereology served to estimate that the PPN of healthy rats unilaterally contains ~19,028 NeuN-immunopositive neurons. The identified neurons revealed a distinct distribution pattern consisting of high cell density in the most rostral and caudal sections of the PPN nucleus, contrasting with lower densities in the medial segments. Our data also show a significant loss which affected PPN non-cholinergic cells, but not cholinergic ones in rats lesioned unilaterally in the Substantia Nigra pars compacta (SNpc) with a single injection of 6-hydroxydopamine (6-OHDA) compared to control animals. This result differs from previous studies which reported a substantial cholinergic cell loss in the PPN of post-mortem PD brains and in 6-OHDA-lesioned monkeys. Since a noted demise of dopaminergic neurons residing in the SN was confirmed in the 6-OHDA-lesioned rats, the current study suggests that a "dying-back" mechanism may underlie the cell death affecting non-cholinergic PPN neurons.


Factors Affecting Cost of Patients with Severe Community-Acquired Pneumonia in Intensive Care Unit.
The aim of this study is to investigate the factors affecting cost in patients with severe community-acquired pneumonia (CAP) who were admitted to the intensive care unit (ICU). This retrospective cohort study was conducted between January 2013 and December 2016. A total of 291 sequential patients with severe CAP were included in the study. Patients' demographic and clinical data; the need for invasive mechanical ventilation or non-invasive mechanical ventilation; intensive care severity (ICU) scores, including Acute Physiology and Chronic Health Evaluation (APACHE II), Sepsis-related Organ Failure Assessment, Quick SOFA, pneumonia severity index (PSI); and Confusion, Urea, Respiratory Rate, and Blood Pressure-65 (CURB-65) scores were obtained from medical records and recorded for all cases. The mean age of 291 patients was 68.4±16.8 years, and 61% were female. The median length of ICU stay was 7 days. Forty-six percent of patients had chronic obstructive pulmonary disease (COPD), and 42% had hypertension. The mean cost of each hospitalization was US$ 2722 (TL 5578). The highest cost was found in the group of patients aged 50-59 years, and the lowest cost was found in the patients aged <50 years. A statistically significant relationship was found between ICU severity scores and health cost. The cost of patients in PSI class V, APACHE II (>20 points), and CURB-65 score were higher. The presence of COPD, atrial fibrillation, congestive heart failure, hypoalbuminemia, mental state deterioration, in-hospital mortality, severe sepsis, septic shock, mechanical ventilation requirement, and haloperidol and vasopressor usage were associated with higher cost, while the use of florokinolon was associated with lower cost. The presence of certain comorbidities and high disease severity in patients with severe CAP hospitalized in ICU increase the cost of inpatient treatment. The need for mechanical ventilation during treatment and the presence of sepsis/septic shock are additional factors that increase the cost.


High-level heterologous expression of fungal cytochrome P450s in Escherichia coli.
A thorough understanding of the sequence-structure-function relationships of cytochrome P450 (P450) is necessary to better understand the metabolic diversity of living organisms. Significant amounts of pure enzymes are sometimes required for biochemical studies, and their acquisition often relies on the possibility of their heterologous expression. In this study, we performed extensive heterologous expression of fungal P450s in Escherichia coli using 304 P450 isoforms. Using large-scale screening, we confirmed that at least 27 P450s could be expressed with/without simple sequence deletion at the 5' end of cDNAs, which encode the N-terminal hydrophobic domain of the enzyme. Moreover, we identified N-terminal amino acid sequences that can potentially be used to construct chimeric P450s, which could dramatically improve their expression levels even when the expression of the wild-type sequence was unpromising. These findings will help increase the chance of heterologous expression of a variety of fungal and other eukaryotic membrane-bound P450s in E. coli.


Evaluation of mobile phase characteristics on three zwitterionic columns in hydrophilic interaction liquid chromatography mode for liquid chromatography-high resolution mass spectrometry based untargeted metabolite profiling of Leishmania parasites.
It has been reported that HILIC column chemistry has a great effect on the number of detected metabolites in LC-HRMS-based untargeted metabolite profiling studies. However, no systematic investigation has been carried out with regard to the optimisation of mobile phase characteristics. In this study using 223 metabolite standards, we explored the retention mechanisms on three zwitterionic columns with varied mobile phase composition, demonstrated the interference from poor chromatographic peak shapes on the output of data extraction, and assessed the quality of chromatographic signals and the separation of isomers under each LC condition. As expected, on the ZIC-cHILIC column the acidic metabolites showed improved chromatographic performance at low pH which can be attributed to the opposite arrangement of the permanently charged groups on this column in comparison with the ZIC-HILIC column. Using extracts from the protozoan parasite Leishmania, we compared the numbers of repeatedly detected LC-HRMS features under different LC conditions with putative identification of metabolites not amongst the standards being based on accurate mass (±3ppm). Besides column chemistry, the pH of the mobile phase plays a key role in not only determining the retention mechanisms of solutes but also the output of the LC-HRMS data processing. Fast evaporation of ammonium carbonate produced less ion suppression in ESI source and consequently improved the detectability of the metabolites in low abundance in comparison with other ammonium salts. Our results show that the combination of a ZIC-pHILIC column with an ammonium carbonate mobile phase, pH 9.2, at 20mM in the aqueous phase or 10mM in both aqueous and organic mobile phase components, provided the most suitable LC conditions for LC-HRMS-based untargeted metabolite profiling of Leishmania parasite extracts. The signal reliability of the mass spectrometer used in this study (Exactive Orbitrap) was also investigated.


Gene amplification in neoplasia: A cytogenetic survey of 80 131 cases.
Gene amplification is a crucial process in cancer development, leading to the overexpression of oncogenes. It manifests cytogenetically as extrachromosomal double minutes (dmin), homogeneously staining regions (hsr), or ring chromosomes (r). This study investigates the prevalence and distribution of these amplification markers in a survey of 80 131 neoplasms spanning hematologic disorders, and benign and malignant solid tumors. The study reveals distinct variations in the frequency of dmin, hsr, and r among different tumor types. Rings were the most common (3.4%) sign of amplification, followed by dmin (1.3%), and hsr (0.8%). Rings were particularly frequent in malignant mesenchymal tumors, especially liposarcomas (47.5%) and osteosarcomas (23.4%), dmin were prevalent in neuroblastoma (30.9%) and pancreatic carcinoma (21.9%), and hsr frequencies were highest in head and neck carcinoma (14.0%) and neuroblastoma (9.0%). Combining all three amplification markers (dmin/hsr/r), malignant solid tumors consistently exhibited higher frequencies than hematologic disorders and benign solid tumors. The structural characteristics of these amplification markers and their potential role in tumorigenesis and tumor progression highlight the complex interplay between cancer-initiating gene-level alterations, for example, fusion genes, and subsequent amplification dynamics. Further research integrating cytogenetic and molecular approaches is warranted to better understand the underlying mechanisms of these amplifications, in particular, the enigmatic question of why certain malignancies display certain types of amplification. Comparing the present results with molecular genetic data proved challenging because of the diversity in definitions of amplification across studies. This study underscores the need for standardized definitions in future work.


Mandibular condylar structure and growth in Macaca fascicularis are related to skeletal rather than dentitional development.
Mandibular condyles of eight male monkeys (Macaca fascicularis), ranging in weight from 1.5 to 3.0 kg, were examined using histometric, radioautographic and stereologic techniques. The animals were classified on the basis of their dentitional and, as judged from radiographs of the hand and wrist, of their skeletal development. This allowed morphometric parameter means to be plotted as a function of four dentitional and five skeletal levels of maturation. The influence of dentitional and skeletal age on total parameter variations was examined by calculating factorial analyses of variance. Although consistent and well defined within each method, condylar parameter changes plotted over skeletal age were essentially different from those over dentitional age. Whereas the latter were difficult, if not impossible, to interpret, the former closely resembled the age-related curves displaying the elongation of short bones of the fingers in M. fascicularis. Furthermore these parameter changes were also consistent with longitudinal alterations in mandibular growth as assessed radiographically in man. The analyses of variance suggested that animals exhibiting the same degree of skeletal as compared to dentitional development, particularly at late stages of maturation, were markedly more homogeneous with respect to the majority of the morphometric parameters examined. Therefore, somatic maturation rather than the stage of tooth eruption should be the basis for estimating biological age in growth studies of the mandibular condyle.


Continuous delivery of endogenous inhibitors from poly(lactic-co-glycolic acid) polymeric microspheres inhibits glioma tumor growth.
There is an urgent need for modalities that can localize and prolong the administration of the antitumor agents, particularly antiangiogenic, to achieve long-term tumor inhibition. However, one of the major obstacles is designing a device in which the biological activity of sensitive endogenous inhibitors is retained. We have designed a biodegradable polymeric device, which provides a unique and practical means of localizing and continuously delivering hemopexin (PEX) or platelet factor 4 fragment (PF-4/CTF) at the tumor site while maintaining their biological activity. The potential and efficacy of this system is shown in vitro and in vivo in a human glioma mouse model. Polymeric microspheres made of poly(lactic-co-glycolic acid) (PLGA) were loaded with very low amounts of PEX and PF-4/CTF. The release profiles of these factors from PLGA and their biological activity were confirmed in vitro using proliferation assays done on endothelial and tumor cells. Tumor inhibition using this system was studied in nude mice bearing a human s.c. glioma. PEX and PF-4/CTF released in vitro from PLGA microspheres were biologically active and significantly inhibited the proliferation of human umbilical vein endothelial cells, bovine capillary endothelial cells, and U87-MG cells. A single local s.c. injection of PLGA microspheres loaded with low amounts of PEX or PF-4/CTF resulted in an 88% and 95% reduction in glioma tumor volume 30 days post-treatment. Immunohistochemical analysis of the treated tumors showed a marked decrease in tumor vessel density compared with untreated tumors. Our findings show that polymeric microspheres are a very promising approach to locally and efficiently deliver endogenous inhibitors to the tumor site leading to a significant inhibition of the tumor.


Methacrylate Resin Adhesion in Root Canals Conditioned with Phosphoric Acid and Ethylenediaminetetraacetic Acid.
The purpose of this study was to determine the ability of a methacrylate resin dentin bonding agent to adhere to the dentin surfaces of prepared and conditioned root canals with either 32% phosphoric acid (PA) or 17% ethylenediaminetetraacetic acid (EDTA). Prior to the application of the methacrylate resin, the root canals of 54 intact, caries-free, single- rooted, de-crowned, extracted human maxillary incisor and canine teeth were endodontically prepared and conditioned with either 32% PA or 17% EDTA or with distilled water as the unconditioned control. The resin-treated roots were cross-sectioned at three levels and scanning electron microscope (SEM) imaged for circumferential views of the root canals at 60-90× magnification and site-specific views at 250× magnification, and then randomly coded for independent and blind evaluation by four calibrated examiners. The circumferential surface of the root canals that showed no resin adhesion were digitally measured and subtracted from the digitally measured total root canal circumference, and resin adhesion was expressed as a percentage of the circumference. The mean percentages of resin adhesion were 97% for the PA group, 94% for the EDTA group, and 76% for the control group. There were statistically significant differences among the PA, EDTA, and control groups. Root canals conditioned with 32% PA or 17% EDTA had more resin adhesion than unconditioned root canals. Root canals conditioned with 32% PA had more resin adhesion than those conditioned with 17% EDTA.


Pathologic appraisal of the thymus gland in acquired immunodeficiency syndrome in children. A study of four cases and a review of the literature.
We studied the entire thymus gland by step-serial sections in four fatal cases of acquired immunodeficiency syndrome (AIDS) in children. The location, configuration, and blood vessels of the thymus gland were normal. The weight was reduced. There was severe depletion of both lymphocytes and Hassall's corpuscles. Because of the normal location, configuration, and blood vessels and the seemingly less severe lymphocytic depletion than is seen in congenital immunodeficiency syndromes and because of the clinical and epidemiologic features, we concluded that this syndrome in children represents AIDS. We postulated that the epithelial cells of the Hassall's corpuscles may be the primary site of thymic injury in AIDS.


Modeling serum biomarkers S100 beta and neuron-specific enolase as predictors of outcome after out-of-hospital cardiac arrest: an aid to clinical decision making.
The aim of this study was to determine the added value of the serum biomarkers S100 and neuron-specific enolase to clinical characteristics for predicting outcome after out-of-hospital cardiac arrest. Serum S100 beta (S100B) and neuron-specific enolase concentrations rise after brain injury. A prolective observational study was conducted among all adult survivors of nontraumatic out-of-hospital cardiac arrest admitted to 1 hospital (April 3, 2008 to April 3, 2011). Three blood samples (on arrival and on days 1 and 3) were drawn for biomarkers, contingent on survival. Follow-up continued until in-hospital death or discharge. Outcomes were defined as good (Cerebral Performance Category score 1 or 2) or poor (Cerebral performance category score 3 to 5). A total of 195 patients were included (65.6% men, mean age 73 ± 16 years), with presenting rhythms of asystole in 61.5% and ventricular tachycardia or ventricular fibrillation in 24.1%. Only 43 patients (22.0%) survived to hospital discharge, 26 (13.3%) with good outcomes. Patients with good outcomes had significantly lower S100B levels at all time points and lower neuron-specific enolase levels on days 1 and 3 compared with those with poor outcomes. Independent predictors at admission of a good outcome were younger age, a presenting rhythm of ventricular tachycardia or ventricular fibrillation, and lower S100B level. Predictors on day 3 were younger age and lower day 3 S100B level. The area under the receiver-operating characteristic curve of the admission-day model was 0.932 with and 0.880 without biomarker data (p = 0.027 for the difference). Risk stratification after out-of-hospital cardiac arrest using both clinical and biomarker data is feasible. The biomarkers, although adding an ostensibly modest 5.2% to the area under the receiver-operating characteristic curve, substantially reduced the level of uncertainty in decision making. Nevertheless, current biomarkers cannot replace societal considerations in determining acceptable levels of uncertainty. (Protein S100 Beta as a Predictor of Resuscitation Outcome; NCT00814814).


Effect of substance P on gene expression of transforming growth factor beta-1 and its receptors in rat's fibroblasts.
To investigate the effect of substance P (SP) on gene expression of transforming growth factor beta-1 (TGFbeta-1), transforming growth factor receptor-1 (TGFR-1) and transforming growth factor receptor-2 (TGFR-2) in fibroblasts cultured in vitro from rat's granulation tissues. The fibroblasts from the granulation tissues in the skeletal muscle of rat's hind limbs injured by formaldehyde were cultured in vitro. When different concentrations (10(-9)-10(-5) mol/L) of SP were added into the culture medium, the changes of gene expression of TGFbeta-1, TGFR-1 and TGFR-2 in the cultured fibroblasts were observed with reverse transcription polymerase chain reaction at different intervals (0, 3, 6, 12 and 24 hours after incubation). The gene expression of TGFbeta-1, TGFR-1 and TGFR-2 in the fibroblasts cultured from rat's granulation tissues was up-regulated by SP. The peak level of the mRNA expression was found at 10(-8) mol/L SP and the up-regulation effect was not found at 10(-5) mol/L and 10(-6) mol/L. The peak levels of gene expression of TGFbeta-1, TGFR-1 and TGFR-2 in the fibroblasts treated with SP were achieved at 6 and 12 hours, respectively. SP has up-regulation effect on the gene expression of TGFbeta-1, TGFR-1 and TGFR-2 in fibroblasts from rat's granulation tissues in vitro, and the effect is related to different stimulating concentrations of SP. It may be concerned with proliferation and differentiation of fibroblasts and formation of scar tissues during wound healing.


Distribution and metabolism of 20 alpha-hydroxylated progestins in the female rat.
The C21 steroids, progesterone and 20 alpha-hydroxy-4-pregnen-3-one (20 alpha-DHP) play pivotal roles in the initiation, timing and maintenance of ovulatory function and pregnancy in female mammals. They also have growth factor and central nervous system (CNS) effects; some of these are non-genomic effects mediated through 5 alpha-reduced and 3 alpha-hydroxylated derivatives. These studies examined the in vivo uptake and conversion of 20 alpha-DHP in selected CNS sites and peripheral tissues after injection of [(3)H]-20 alpha-DHP. The effects of steroid mass, time after injection, and ovariectomy, adrenalectomy and estradiol treatment were assessed in the pineal gland, preoptic area of the hypothalamus (POA), medial basal hypothalamus (MBH), midbrain, cerebellum, cerebral cortex, anterior pituitary (AP), uterus and skeletal muscle. Tissue extracts were analyzed by scintillation counting and chromatography to quantify and localize 20 alpha-DHP and its 5 alpha-reduced derivatives. Injection of increasing mass of [(3)H]-20 alpha-DHP to ovariectomized/adrenalectomized (ovx/adx) rats results in a linear increase in (3)H-steroid 10 min post injection in all tissues. (3)H-steroid content increases with time over 1 h post injection in the pineal, AP and uterus. Tissue differences in (3)H-steroid level are observed with higher levels in pineal, MBH, POA, AP and midbrain than in cerebral cortex and cerebellum, and in uterus, ovary and adrenal than in muscle. Ovariectomy, adrenalectomy and estradiol treatment affect (3)H-steroid levels in a tissue dependent manner, and the metabolites of 20 alpha-DHP in MBH and AP differ between groups. The findings demonstrate that target tissues, including areas of the CNS, are able to selectively take up and retain 20 alpha-DHP, and also support a physiological role for this progestin and its metabolites in modulation of CNS and reproductive functions.


Topical Diclofenac-Induced Hepatotoxicity.
The hepatotoxic potential of diclofenac, a commonly used non-steroidal anti-inflammatory agent, is well established in literature. However, cases of diclofenac-induced liver disease have occurred almost exclusively with the oral formulation of this medication. We report the case of an elderly man with Paget's disease and osteoarthritis who developed acute hepatotoxicity, as evidenced by laboratory diagnostics, four months after use of topical diclofenac 1% gel. Once diclofenac gel was discontinued, repeat blood work three weeks after discharge demonstrated return of liver function tests to baseline. Given the temporal relationship between the initiation and escalation of topical diclofenac and the changes in liver function tests, the likelihood of diclofenac-induced liver injury was deemed possible using a well-recognized causality assessment tool. Further research on topically administered non-steroidal anti-inflammatory agents is needed to identify monitoring intervals for early detection and avoidance of adverse effects in patients using topical diclofenac.


The Pediatrics Milestones Assessment Pilot: Development of Workplace-Based Assessment Content, Instruments, and Processes.
To report on the development of content and user feedback regarding the assessment process and utility of the workplace-based assessment instruments of the Pediatrics Milestones Assessment Pilot (PMAP). One multisource feedback instrument and two structured clinical observation instruments were developed and refined by experts in pediatrics and assessment to provide evidence for nine competencies based on the Pediatrics Milestones (PMs) and chosen to inform residency program faculty decisions about learners' readiness to serve as pediatric interns in the inpatient setting. During the 2012-2013 PMAP study, 18 U.S. pediatric residency programs enrolled interns and subinterns. Faculty, residents, nurses, and other observers used the instruments to assess learner performance through direct observation during a one-month rotation. At the end of the rotation, data were aggregated for each learner, milestone levels were assigned using a milestone classification form, and feedback was provided to learners. Learners and site leads were surveyed and/or interviewed about their experience as participants. Across the sites, 2,338 instruments assessing 239 learners were completed by 630 unique observers. Regarding end-of-rotation feedback, 93% of learners (128/137) agreed the assessments and feedback "helped me understand how those with whom I work perceive my performance," and 85% (117/137) agreed they were "useful for constructing future goals or identifying a developmental path." Site leads identified several benefits and challenges to the assessment process. PM-based instruments used in workplace-based assessment provide a meaningful and acceptable approach to collecting evidence of learner competency development. Learners valued feedback provided by PM-based assessment.


The FASSET framework for assessment of environmental impact of ionising radiation in European ecosystems--an overview.
The FASSET project was launched in November 2000 under the EC 5th Framework Programme to develop a framework for the assessment of environmental impact of ionising radiation in European ecosystems. It involved 15 organisations in seven European countries and delivered its final report in spring 2004. The project set out to organise radioecological and radiobiological data into a logical structure that would facilitate the assessment of likely effects on non-human biota resulting from known or postulated depositions of radionuclides in the environment. The project included an overview of 20 pathway-based environmental assessment systems targeted at radioactive substances, or at hazardous substances in general. The resulting framework includes the following fundamental elements: source characterisation; description of seven major European ecosystems; selection of a number of reference organisms on the basis of prior ecosystem and exposure analysis; environmental transfer analysis; dosimetric considerations; effects analysis; and general guidance on interpretation including consideration of uncertainties. The project has used existing information supplemented with development in some areas, e.g. Monte Carlo calculations to derive dose conversion coefficients, model development, and the building of an effects database (FRED, the FASSET Radiation Effects Database). On the basis of experience from FASSET and other recent programmes, it can be concluded that (i) there is substantial agreement in terms of conceptual approaches between different frameworks currently in use or proposed, (ii) differences in technical approaches can be largely attributed to differences in ecosystems of concern or in national regulatory requirements, (iii) sufficient knowledge is available to scientifically justify assessments following the Framework structure, but (iv) significant data gaps exist for environmental transfer of key nuclides as well as for effects data for key wildlife groups at environmentally relevant dose rates. This paper briefly describes the overall content of the FASSET Framework, as well as highlighting a few important future challenges.


The effect of periodic disturbances and carrying capacity on the significance of selection and drift in complex bacterial communities.
Understanding how periodical disturbances affect the community assembly processes is vital for predicting temporal dynamics in microbial communities. However, the effect of dilutions as disturbances are poorly understood. We used a marine bacterial community to investigate the effect of disturbance (+/-) and carrying capacity (high/low) over 50 days in a dispersal-limited 2 × 2 factorial study in triplicates, with a crossover in the disturbance regime between microcosms halfway in the experiment. We modelled the rate of change in community composition between replicates and used this rate to quantify selection and ecological drift. The disturbed communities increased in Bray-Curtis similarity with 0.011 ± 0.0045 (Period 1) and 0.0092 ± 0.0080 day-1 (Period 2), indicating that selection dominated community assembly. The undisturbed communities decreased in similarity at a rate of -0.015 ± 0.0038 day-1 in Period 1 and were stable in Period 2 at 0.00050 ± 0.0040 day-1, suggesting drift structured community assembly. Interestingly, carrying capacity had minor effects on community dynamics. This study is the first to show that stochastic effects are suppressed by periodical disturbances resulting in exponential growth periods due to density-independent biomass loss and resource input. The increased contribution of selection as a response to disturbances implies that ecosystem prediction is achievable.


Toward Best Practice in Using Molecular Diagnosis to Guide Medical Management, Are We There Yet?
Molecular genetics testing has made several huge breakthroughs in the past two decades and many molecular technologies have been applied to our daily medical progress. However, the clinical utility has not reach a consensus by the medical and genetic peers as well as third party payers. The predictive value and clinical applications are variable from one condition to the other. Numerous questions remain including technology deficits, data interpretation and unpredicted phenotypes in complex disorders. In this commentary, the authors reviewed the historical perspective of genetic testing and summarized the current technical deficit, clinical dilemma and suggested a few critical threshold to overcome before the implementation of useful genetic information in standard health care can become a reality.


The knee kinematic patterns and associated factors in healthy Thai adults.
Reference values for normal knee kinematics were limited in Asian population and were influenced by race and other factors. This study was aimed to establish the reference values and identify the factors associated with knee kinematics in healthy Thai adults, aged 18-40 years. A retrospective cohort study was conducted between 2016 and 2020. Healthy Thai adults aged 18-40 years old with body mass index (BMI) between 18.5 and 24.9 kg/m2 were included. All eligible participants were attached with reflective markers. Their walking was captured by 8-digital cameras, and assessed by motion analysis software. The primary outcomes were average knee kinematic data (degrees) in three dimensional planes as valgus-varus, flexion-extension, and internal-external rotation. Paired t-test and multiple linear regression were applied to compare the outcomes and to determine their associated factors. Ninety-eight participants (60 females and 38 males) were included with mean age 28.5 ± 5.4 years, and BMI 21.1 ± 2.0 kg/m2. Knee kinematics showed slight adduction during the swing phase, flexion during the stance phase, and obvious external rotation throughout the gait cycle, with a peak of 30-31 degrees during mid-swing. Right knee was significantly more adducted, flexed and externally rotated than the left side, particularly at mid-stance (P = 0.047, 0.017, and < 0.001, respectively). Females had more knee abduction, flexion and external rotation than males. Age, sex, and BMI were significantly correlated with knee abduction at terminal stance (correlation coefficient - 0.12, 95% confidence interval (CI) -0.23, -0.01; -1.37, 95%CI -2.54, -0.20; and - 0.32, 95%CI -0.61, -0.39, respectively), and rotation at mid-swing (correlation coefficient - 0.36, 95%CI -0.69, -0.02; -7.37, 95%CI -10.82, -3.92; and 0.89, 95%CI 0.01, 1.78, respectively). Knee kinematics demonstrates external tibial rotation throughout the gait cycle, significant side differences, and are associated with age, sex, and BMI. Reference values from this study will be useful for functional gait assessment in healthy Thais. However, further comprehensive knee kinetic study including spatio-temporal parameter is recommended.


Coverage and quality of oral cancer information in selected popular press: May 1998 to July 2003.
A 1998 study demonstrated a lack of coverage about oral cancer in the popular press between April 1987 and April 1997. Since that study, several oral cancer-related activities took place, many of which could have increased the media's attention to oral cancer. Therefore, this study analyzed coverage and quality of oral cancer information in selected popular press between May 1998 and July 2003. Articles from magazines and newspapers were retrieved from three databases and were analyzed by specific topics and subtopics for adequacy of content and accuracy of information. Articles were categorized as either "primarily oral cancer-related" or "primarily tobacco-related." Sixty articles were identified, 39 of which were included in the analysis (14 magazines; 25 newspapers). Seventeen articles were "primarily oral cancer-related," and 22 were "primarily tobacco-related." Seventy-two percent of the articles mentioned at least one risk factor for oral cancer, the most common being tobacco use (69%). Far fewer articles noted alcohol (10%) or the combined use of tobacco and alcohol (5%) as risk factors. Only 8 percent of the articles recommended an oral cancer examination. Despite local and limited national efforts and activities aimed at increasing public awareness of oral cancer, the popular press coverage of those activities was minimal or nonexistent.


Why do intimate partners live apart? Evidence on LAT relationships across Europe.
Most research asks whether or not cohabitation has come to rival marriage. Little is known about the meaning of living apart together (LAT) relationships, and whether LAT is an alternative to marriage and cohabitation or a dating relationship. We examine across Europe: (1) the prevalence of LAT, (2) the reasons for LAT, and (3) the correlates of (a) LAT relationships vis-à-vis being single, married, or cohabiting, and (b) different types of LAT union. Using Generations and Gender Survey data from ten Western and Eastern European countries, we present descriptive statistics about LATs and estimate multinominal logistic regression models to assess the correlates of being in different types of LAT unions. LAT relationships are uncommon, but they are more common in Western than Eastern Europe. Most people in LAT unions intend to live together but are apart for practical reasons. LAT is more common among young people, those enrolled in higher education, people with liberal attitudes, highly educated people, and those who have previously cohabited or been married. Older people and divorced or widowed persons are more likely to choose LAT to maintain independence. Surprisingly, attitudinal and educational differences are more pronounced in Eastern Europe than in Western Europe. A tentative conclusion is that LAT is more often a stage in the union formation process than an alternative to marriage and cohabitation. Yet some groups do view LAT as substituting for marriage and cohabitation, and these groups differ between East and West. In Eastern Europe a cultural, highly educated elite seems to be the first to resist traditional marriage norms and embrace LAT (and cohabitation) as alternative living arrangements, whereas this is less the case in Western Europe. In Western Europe, LAT unions are mainly an alternative for persons who have been married before or had children in a prior relationship.


Estrogen receptor-beta sensitizes breast cancer cells to the anti-estrogenic actions of endoxifen.
We have previously demonstrated that endoxifen is the most important tamoxifen metabolite responsible for eliciting the anti-estrogenic effects of this drug in breast cancer cells expressing estrogen receptor-alpha (ERα). However, the relevance of ERβ in mediating endoxifen action has yet to be explored. Here, we characterize the molecular actions of endoxifen in breast cancer cells expressing ERβ and examine its effectiveness as an anti-estrogenic agent in these cell lines. MCF7, Hs578T and U2OS cells were stably transfected with full-length ERβ. ERβ protein stability, dimer formation with ERα and expression of known ER target genes were characterized following endoxifen exposure. The ability of various endoxifen concentrations to block estrogen-induced proliferation of MCF7 parental and ERβ-expressing cells was determined. The global gene expression profiles of these two cell lines was monitored following estrogen and endoxifen exposure and biological pathway analysis of these data sets was conducted to identify altered cellular processes. Our data demonstrate that endoxifen stabilizes ERβ protein, unlike its targeted degradation of ERα, and induces ERα/ERβ heterodimerization in a concentration dependent manner. Endoxifen is also shown to be a more potent inhibitor of estrogen target genes when ERβ is expressed. Additionally, low concentrations of endoxifen observed in tamoxifen treated patients with deficient CYP2D6 activity (20 to 40 nM) markedly inhibit estrogen-induced cell proliferation rates in the presence of ERβ, whereas much higher endoxifen concentrations are needed when ERβ is absent. Microarray analyses reveal substantial differences in the global gene expression profiles induced by endoxifen at low concentrations (40 nM) when comparing MCF7 cells which express ERβ to those that do not. These profiles implicate pathways related to cell proliferation and apoptosis in mediating endoxifen effectiveness at these lower concentrations. Taken together, these data demonstrate that the presence of ERβ enhances the sensitivity of breast cancer cells to the anti-estrogenic effects of endoxifen likely through the molecular actions of ERα/β heterodimers. These findings underscore the need to further elucidate the role of ERβ in the biology and treatment of breast cancer and suggest that the importance of pharmacologic variation in endoxifen concentrations may differ according to ERβ expression.