Src tyrosine kinase inhibition prevents pulmonary ischemia-reperfusion-induced acute lung injury.
Pulmonary ischemia-reperfusion is a pathological process seen in several clinical conditions, including lung transplantation, cardiopulmonary bypass, resuscitation for circulatory arrest, atherosclerosis, and pulmonary embolism. A better understanding of its molecular mechanisms is very important. Rat left lung underwent in situ ischemia for 60 min, followed by 2 h of reperfusion. The gene expression profiles and Src protein tyrosine kinase (PTK) phosphorylation were studied over time, and PP2, an Src PTK inhibitor, was intravenously administered 10 min before lung ischemia to determine the role of Src PTK in lung injury. Reperfusion following ischemia significantly changed the expression of 169 genes, with Mmp8, Mmp9, S100a9, and S100a8 being the most upregulated genes. Ischemia alone only affected expression of 9 genes in the lung. However, Src PTK phosphorylation (activation) was increased in the ischemic lung, mainly on the alveolar wall. Src PTK inhibitor pretreatment decreased phosphorylation of Src PTKs, total protein tyrosine phosphorylation, and STAT3 phosphorylation. It increased phosphorylation of the p85α subunit of PI3 kinase, a signal pathway that can inhibit coagulation and inflammation. PP2 reduced leukocyte infiltration in the lung, apoptotic cell death, fibrin deposition, and severity of acute lung injury after reperfusion. Src inhibition also significantly reduced CXCL1 (GRO/KI) and CCL2 (MCP-1) chemokine levels in the serum. During pulmonary ischemia, Src PTK activation, rather than alteration in gene expression, may play a critical role in reperfusion-induced lung injury. Src PTK inhibition presents a new prophylactic treatment for pulmonary ischemia-reperfusion-induced acute lung injury.


Coffee and non-alcoholic fatty liver disease: brewing evidence for hepatoprotection?
Coffee is one of the most popular beverages in the world. Several studies consistently show that coffee drinkers with chronic liver disease have a reduced risk of cirrhosis and a lower incidence of hepatocellular carcinoma regardless of primary etiology. With the increasing prevalence of non-alcoholic fatty liver disease (NAFLD) worldwide, there is renewed interest in the effect of coffee intake on NAFLD severity and positive clinical outcomes. This review gives an overview of growing epidemiological and clinical evidence which indicate that coffee consumption reduces severity of NAFLD. These studies vary in methodology, and potential confounding factors have not always been completely excluded. However, it does appear that coffee, and particular components other than caffeine, reduce NAFLD prevalence and inflammation of non-alcoholic steatohepatitis. Several possible mechanisms underlying coffee's hepatoprotective effects in NAFLD include antioxidative, anti-inflammatory, and antifibrotic effects, while a chemopreventive effect against hepatocarcinogenesis seems likely. The so-far limited data supporting such effects will be discussed, and the need for further study is highlighted.


Kdm6b regulates context-dependent hematopoietic stem cell self-renewal and leukemogenesis.
The histone demethylase KDM6B (JMJD3) is upregulated in blood disorders, suggesting that it may have important pathogenic functions. Here we examined the function of Kdm6b in hematopoietic stem cells (HSC) to evaluate its potential as a therapeutic target. Loss of Kdm6b lead to depletion of phenotypic and functional HSCs in adult mice, and Kdm6b is necessary for HSC self-renewal in response to inflammatory and proliferative stress. Loss of Kdm6b leads to a pro-differentiation poised state in HSCs due to the increased expression of the AP-1 transcription factor complex (Fos and Jun) and immediate early response (IER) genes. These gene expression changes occurred independently of chromatin modifications. Targeting AP-1 restored function of Kdm6b-deficient HSCs, suggesting that Kdm6b regulates this complex during HSC stress response. We also show Kdm6b supports developmental context-dependent leukemogenesis for T-cell acute lymphoblastic leukemia (T-ALL) and M5 acute myeloid leukemia (AML). Kdm6b is required for effective fetal-derived T-ALL and adult-derived AML, but not vice versa. These studies identify a crucial role for Kdm6b in regulating HSC self-renewal in different contexts, and highlight the potential of KDM6B as a therapeutic target in different hematopoietic malignancies.


The South London Somatisation Study. II. Influence of stressful life events, and secondary gain.
A study of the influence of life-event stress on the onset and course of acute somatisation in primary care. Forty-four somatisers were compared with 11 subjects who had psychiatric disorder but complained only of psychological symptoms, 39 patients who had 'mixed' conditions involving independent physical and psychiatric illness, 90 patients who had physical illness, and 123 healthy members of the general population. Severely threatening life events were more common among all subjects with psychiatric disorder. A novel contextual rating of the potential of stressors to produce symptoms for 'secondary gain' was developed. In the 38 weeks before symptom onset, somatisers and psychologisers were more likely to have experienced at least one event which had this potential. Somatisers were also less likely to adopt neutralising coping efforts when faced with such a crisis. The likelihood of adopting neutralising efforts was closely related to the presence of a joint index of parental problems in care and exposure to physical illness in the subject's childhood. In a two-year follow-up, subsequent functional illnesses were also associated with experiences which had secondary-gain potential, and subjects with childhood risk factors continued to have higher rates of crises with secondary-gain potential and to fail to adopt neutralising coping strategies.


Association of serum osteoprotegerin with vascular calcification in patients with type 2 diabetes.
Osteoprotegerin is a member of the tumor necrosis factor-related family and inhibits RANK stimulation of osteoclast formation as a soluble decoy receptor. The goal of this study was to determine the relationship of serum osteoprotegerin with vascular calcification in patients with type 2 diabetes. The subjects were 124 patients with type 2 diabetes mellitus, including 88 males and 36 females with a mean (± SD) age of 65.6 ± 8.2 years old. Serum levels of osteoprotegerin, osteocalcin, fibroblast growth factor 23 (FGF23), 25-hydroxyvitamin D3 and adiponectin were measured by ELISA. Vascular calcification in the cervical artery was examined by ultrasound sonography. The subjects were divided into 4 quartiles depending on serum osteoprotegerin levels. Vascular calcification was significantly higher in the 4th quartile and significantly lower in the 1st quartile of serum osteoprotegerin levels, compared to other quartiles. There were no differences in serum osteoprotegerin and vascular calcification among patients with different stages of diabetic nephropathy, but serum FGF23 levels were elevated in those with stage 4 diabetic nephropathy. Simple regression analysis showed that serum osteoprotegerin levels had significant positive correlations with age, systolic blood pressure and serum adiponectin levels, and significant negative correlations with BMI and serum 25-hydroxyvitamin D3. These findings suggest that elevated serum osteoprotegerin may be involved in vascular calcification independently of progression of diabetic nephropathy in patients with type 2 diabetes.


Identification of live germ-cell desquamation as a major mechanism of seasonal testis regression in mammals: a study in the Iberian mole (Talpa occidentalis).
In males of seasonally breeding species, testes undergo a severe involution at the end of the breeding season, with a major volume decrease due to massive germ-cell depletion associated with photoperiod-dependent reduced levels of testosterone and gonadotropins. Although it has been repeatedly suggested that apoptosis is the principal effector of testicular regression in vertebrates, recent studies do not support this hypothesis in some mammals. The purpose of our work is to discover alternative mechanisms of testis regression in these species. In this paper, we have performed a morphological, hormonal, ultrastructural, molecular, and functional study of the mechanism of testicular regression and the role that cell junctions play in the cell-content dynamics of the testis of the Iberian mole, Talpa occidentalis, throughout the seasonal breeding cycle. Desquamation of live, nonapoptotic germ cells has been identified here as a new mechanism for seasonal testis involution in mammals, indicating that testis regression is regulated by modulating the expression and distribution of the cell-adhesion molecules in the seminiferous epithelium. During this process, which is mediated by low intratesticular testosterone levels, Sertoli cells lose their nursing and supporting function, as well as the impermeability of the blood-testis barrier. Our results contradict the current paradigm that apoptosis is the major testis regression effector in vertebrates, as it is clearly not true in all mammals. The new testis regression mechanism described here for the mole could then be generalized to other mammalian species. Available data from some previously studied mammals should be reevaluated.


GSK-3beta inhibition reverses axonal transport defects and behavioural phenotypes in Drosophila.
The tauopathies are a group of disorders characterised by aggregation of the microtubule-associated protein tau and include Alzheimer's disease (AD) and the fronto-temporal dementias (FTD). We have used Drosophila to analyse how tau abnormalities cause neurodegeneration. By selectively co-expressing wild-type human tau (0N3R isoform) and a GFP vesicle marker in motorneurons, we examined the consequences of tau overexpression on axonal transport in vivo. The results show that overexpression of tau disrupts axonal transport causing vesicle aggregation and this is associated with loss of locomotor function. All these effects occur without neuron death. Co-expression of constitutively active glycogen-synthase kinase-3beta (GSK-3beta) enhances and two GSK-3beta inhibitors, lithium and AR-A014418, reverse both the axon transport and locomotor phenotypes, suggesting that the pathological effects of tau are phosphorylation dependent. These data show that tau abnormalities significantly disrupt neuronal function, in a phosphorylation-dependent manner, before the classical pathological hallmarks are evident and also suggest that the inhibition of GSK-3beta might have potential therapeutic benefits in tauopathies.


A Single Dose of 5-MeO-DMT Stimulates Cell Proliferation, Neuronal Survivability, Morphological and Functional Changes in Adult Mice Ventral Dentate Gyrus.
The subgranular zone (SGZ) of dentate gyrus (DG) is one of the few regions in which neurogenesis is maintained throughout adulthood. It is believed that newborn neurons in this region encode temporal information about partially overlapping contextual memories. The 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a naturally occurring compound capable of inducing a powerful psychedelic state. Recently, it has been suggested that DMT analogs may be used in the treatment of mood disorders. Due to the strong link between altered neurogenesis and mood disorders, we tested whether 5-MeO-DMT is capable of increasing DG cell proliferation. We show that a single intracerebroventricular (ICV) injection of 5-MeO-DMT increases the number of Bromodeoxyuridine (BrdU+) cells in adult mice DG. Moreover, using a transgenic animal expressing tamoxifen-dependent Cre recombinase under doublecortin promoter, we found that 5 Meo-DMT treated mice had a higher number of newborn DG Granule cells (GC). We also showed that these DG GC have more complex dendritic morphology after 5-MeO-DMT. Lastly, newborn GC treated with 5-MeO-DMT, display shorter afterhyperpolarization (AHP) potentials and higher action potential (AP) threshold compared. Our findings show that 5-MeO-DMT affects neurogenesis and this effect may contribute to the known antidepressant properties of DMT-derived compounds.


Lateral Tibial Posterior Slope Is Increased in Patients With Early Graft Failure After Anterior Cruciate Ligament Reconstruction.
The lateral tibial posterior slope (LTPS) has been reported in multiple studies to correlate with an increased risk for native anterior cruciate ligament (ACL) tearing. To date, no study has examined the effect of an increased LTPS as measured on magnetic resonance imaging (MRI) on the likelihood of ACL graft failure. An increased LTPS as measured on MRI would correlate with an increased risk for ACL graft failure. Case-control study; Level of evidence, 3. Fifty-eight patients were initially identified who experienced graft failure after primary ACL reconstruction and underwent revision between 1998 and 2009. Exclusion criteria were clinical follow-up of less than 4 years, graft failure occurring greater than 2 years after primary surgery, skeletal immaturity, deep infection, lack of available preoperative MRI, and history of trauma to the proximal tibia. This left 35 patients with early (within 2 years) failure of primary ACL reconstruction. These patients were matched to 35 control participants who had undergone ACL reconstruction with a minimum of 4 years of clinical follow-up and no evidence of graft failure. Patients were matched by age, sex, date of primary surgery, and graft type. The LTPS was then determined on MRI in a blinded fashion. The mean time to failure in patients in the study group was 1 year (range, 0.6-1.4 years). The mean follow-up of those in the matched control group was 6.9 years (range, 4.0-13.9 years). The mean LTPS in the early ACL failure group was found to be 8.4°, which was significantly larger than that in the control group at 6.5° (P = .012). The odds ratio for graft failure considering a 2° increase in the LTPS was 1.6 (95% CI, 1.1-2.2) and continued to increase to 2.4 (95% CI, 1.2-5.0) and 3.8 (95% CI, 1.3-11.3) with 4° and 6° increases in the LTPS, respectively. No significant association was identified between graft type and graft failure. An increased LTPS is associated with an increased risk for early ACL graft failure, regardless of graft type. Orthopaedic surgeons should consider measuring the LTPS as part of the preoperative assessment of ACL-injured patients.


Recombinant amyloid beta-peptide production by coexpression with an affibody ligand.
Oligomeric and fibrillar aggregates of the amyloid beta-peptide (Abeta) have been implicated in the pathogenesis of Alzheimer's disease (AD). The characterization of Abeta assemblies is essential for the elucidation of the mechanisms of Abeta neurotoxicity, but requires large quantities of pure peptide. Here we describe a novel approach to the recombinant production of Abeta. The method is based on the coexpression of the affibody protein ZAbeta3, a selected affinity ligand derived from the Z domain three-helix bundle scaffold. ZAbeta3 binds to the amyloidogenic central and C-terminal part of Abeta with nanomolar affinity and consequently inhibits aggregation. Coexpression of ZAbeta3 affords the overexpression of both major Abeta isoforms, Abeta(1-40) and Abeta(1-42), yielding 4 or 3 mg, respectively, of pure 15N-labeled peptide per liter of culture. The method does not rely on a protein-fusion or -tag and thus does not require a cleavage reaction. The purified peptides were characterized by NMR, circular dichroism, SDS-PAGE and size exclusion chromatography, and their aggregation propensities were assessed by thioflavin T fluorescence and electron microscopy. The data coincide with those reported previously for monomeric, largely unstructured Abeta. ZAbeta3 coexpression moreover permits the recombinant production of Abeta(1-42) carrying the Arctic (E22G) mutation, which causes early onset familial AD. Abeta(1-42)E22G is obtained in predominantly monomeric form and suitable, e.g., for NMR studies. The coexpression of an engineered aggregation-inhibiting binding protein offers a novel route to the recombinant production of amyloidogenic Abeta peptides that can be advantageously employed to study the molecular basis of AD. The presented expression system is the first for which expression and purification of the aggregation-prone Arctic variant (E22G) of Abeta(1-42) is reported.


Fresnelets: new multiresolution wavelet bases for digital holography.
We propose a construction of new wavelet-like bases that are well suited for the reconstruction and processing of optically generated Fresnel holograms recorded on CCD-arrays. The starting point is a wavelet basis of L2 to which we apply a unitary Fresnel transform. The transformed basis functions are shift-invariant on a level-by-level basis but their multiresolution properties are governed by the special form that the dilation operator takes in the Fresnel domain. We derive a Heisenberg-like uncertainty relation that relates the localization of Fresnelets with that of their associated wavelet basis. According to this criterion, the optimal functions for digital hologram processing turn out to be Gabor functions, bringing together two separate aspects of the holography inventor's work. We give the explicit expression of orthogonal and semi-orthogonal Fresnelet bases corresponding to polynomial spline wavelets. This special choice of Fresnelets is motivated by their near-optimal localization properties and their approximation characteristics. We then present an efficient multiresolution Fresnel transform algorithm, the Fresnelet transform. This algorithm allows for the reconstruction (backpropagation) of complex scalar waves at several user-defined, wavelength-independent resolutions. Furthermore, when reconstructing numerical holograms, the subband decomposition of the Fresnelet transform naturally separates the image to reconstruct from the unwanted zero-order and twin image terms. This greatly facilitates their suppression. We show results of experiments carried out on both synthetic (simulated) data sets as well as on digitally acquired holograms.


Concurrent recordings of bladder afferents from multiple nerves using a microfabricated PDMS microchannel electrode array.
In this paper we present a compliant neural interface designed to record bladder afferent activity. We developed the implant's microfabrication process using multiple layers of silicone rubber and thin metal so that a gold microelectrode array is embedded within four parallel polydimethylsiloxane (PDMS) microchannels (5 mm long, 100 μm wide, 100 μm deep). Electrode impedance at 1 kHz was optimized using a reactive ion etching (RIE) step, which increased the porosity of the electrode surface. The electrodes did not deteriorate after a 3 month immersion in phosphate buffered saline (PBS) at 37 °C. Due to the unique microscopic topography of the metal film on PDMS, the electrodes are extremely compliant and can withstand handling during implantation (twisting and bending) without electrical failure. The device was transplanted acutely to anaesthetized rats, and strands of the dorsal branch of roots L6 and S1 were surgically teased and inserted in three microchannels under saline immersion to allow for simultaneous in vivo recordings in an acute setting. We utilized a tripole electrode configuration to maintain background noise low and improve the signal to noise ratio. The device could distinguish two types of afferent nerve activity related to increasing bladder filling and contraction. To our knowledge, this is the first report of multichannel recordings of bladder afferent activity.


Organizational Context and Capabilities for Integrating Care: A Framework for Improvement.
Interventions aimed at integrating care have become widespread in healthcare; however, there is significant variability in their success. Differences in organizational contexts and associated capabilities may be responsible for some of this variability. This study develops and validates a conceptual framework of organizational capabilities for integrating care, identifies which of these capabilities may be most important, and explores the mechanisms by which they influence integrated care efforts. The Context and Capabilities for Integrating Care (CCIC) Framework was developed through a literature review, and revised and validated through interviews with leaders and care providers engaged in integrated care networks in Ontario, Canada. Interviews involved open-ended questions and graphic elicitation. Quantitative content analysis was used to summarize the data. The CCIC Framework consists of eighteen organizational factors in three categories: Basic Structures, People and Values, and Key Processes. The three most important capabilities shaping the capacity of organizations to implement integrated care interventions include Leadership Approach, Clinician Engagement and Leadership, and Readiness for Change. The majority of hypothesized relationships among organizational capabilities involved Readiness for Change and Partnering, emphasizing the complexity, interrelatedness and importance of these two factors to integrated care efforts. Organizational leaders can use the framework to determine readiness to integrate care, develop targeted change management strategies, and select appropriate partners with overlapping or complementary profiles on key capabilities. Researchers may use the results to test and refine the proposed framework, with a focus on the hypothesized relationships among organizational capabilities and between organizational capabilities and performance outcomes.


I know you are, but what am I? Self-evaluative consequences of judging in-group and out-group members.
When judging another person, people often spontaneously compare this person with themselves. Six studies examined the self-evaluative consequences of such spontaneous comparisons with in-group versus out-group members. They demonstrate that spontaneous comparisons with in-group members primarily involved the activation of specific individuating knowledge about the self. In particular, knowledge indicating that the self is similar to the judged target was rendered accessible. As a consequence, subsequent self-evaluations that were based on the implications of accessible self-knowledge were assimilated toward in-group targets. Spontaneous comparisons with out-group members, however, primarily involved the activation of more general category knowledge about the self. Specifically, knowledge about judges' membership in a group that distinguished them from the target was rendered accessible. Consequently, self-evaluations were contrasted away from out-group targets.


Different mechanisms contribute to the E2-mediated transcriptional repression of human papillomavirus type 18 viral oncogenes.
Transcription of the human papillomavirus type 18 (HPV18) E6 and E7 oncogenes is repressed by the viral E2 protein. In C33 cells, we have previously shown that of the four E2 binding sites (E2 BS) present in the HPV18 long control region (LCR), only the binding site adjacent to the TATA box (E2 BS 1) was involved in E2-mediated repression. In the present study, we sought to determine whether this phenomenon was conserved in other cell lines. We first showed that all three E2 BS proximal to the P105 promoter were required for full repression of its activity in HeLa and HaCaT cells. Repression by E2 at E2 BS 2 occurred through the displacement of Sp1. Second, a truncated E2 product, lacking the N-terminal transactivation domain, repressed transcription more efficiently than the full-length protein. Repression was abolished when the N-terminal domain of E2 was replaced by the activation domain of VP16. The VP16-E2 chimeric protein could activate transcription from an LCR mutated in its TATA box. DNA-protein binding studies showed that E2 associates with its four binding sites in the LCR with similar affinities. However, challenge of such complexes with excess binding sites demonstrated that interaction with E2 BS 4 was the most stable while interaction with E2 BS 1 was the least stable. Furthermore, complexes with the full-length E2 were less stable than those formed with the N-terminally truncated protein.


Hepatosplenic morbidity in schistosomiasis japonica: evaluation with Doppler sonography.
In Southeast Asia, schistosomiasis japonica is an important cause of hepatic fibrosis and gastrointestinal hemorrhage. Reliable methods to investigate portal hypertension (PHT) clinically and epidemiologically on community level are lacking. Doppler sonography is an established tool for investigating PHT in hospital settings. In Leyte, The Philippines, 137 individuals underwent color Doppler sonography, stool examination, and serology for hepatitis B and C, liver cell injury and cholestasis. A total of 85% of the study population had been infected with Schistosoma japonicum. Sonographically, periportal liver fibrosis was seen in 25% and reticular echogenicities (network pattern) in 44%. Portal blood flow was decreased or portosystemic collaterals were present in 10% (adults throughout) and correlated with periportal fibrosis, but not with network lesions. Chronic viral hepatitis was rare. Thus, hepatic lesions are frequent in adults but not in children in areas endemic for S. japonicum. Periportal liver fibrosis indicates a risk of PHT, and network pattern fibrosis apparently does not. Doppler sonography is suitable for research under tropical field conditions.


Rapid changes in gene expression after in vivo growth hormone treatment.
GH exerts long-lasting effects on somatic growth via changes in gene expression and protein biosynthesis that represent the culmination of signal transduction pathways initiated at the cell surface. Recent studies have demonstrated that ligand-induced activation of the GH receptor leads to the phosphorylation of multiple intracellular proteins, including latent cytoplasmic transcription factors, Stats 1 and 3. GH treatment also has been found to induce the expression of several genes in both in vitro and in vivo systems, and we have shown that GH rapidly activates insulin-like growth factor I (IGF-I) gene transcription in hypophysectomized rats. In this study, using the GH-deficient, hypophysectomized rat as a model, we have examined the earliest changes in gene expression that follow a single systemic injection of GH. We find that GH induces nascent nuclear IGF-I transcripts within 15 min of hormone treatment, a time course that parallels the GH-regulated appearance of nuclear c-fos messenger RNA (mRNA). By contrast, nuclear transcripts for c-jun did not increase in abundance until after 30 min after hormone injection, and the peak rise in c-jun mRNA was severalfold less than for c-fos or IGF-I. GH treatment also led to the acute inhibition of IGF binding protein-1 (IGFBP-1) and albumin gene expression. Nuclear IGFBP-1 mRNA levels declined to 60% of baseline at 30 min and to 30% at 60 min, in agreement with previous studies showing a reduction in IGFBP-1 transcription after GH. Nascent nuclear albumin transcripts also decreased in abundance after GH treatment to levels that were less than 20% of basal values at 30 and 60 min. Our results show that GH can acutely activate and inhibit gene expression in the liver. It is likely that these diverse effects of GH are mediated by multiple signal transduction pathways.


Suppression of apoptosis signal-regulating kinase 1-induced cell death by 14-3-3 proteins.
Apoptosis signal-regulating kinase 1 (ASK1) is a pivotal component of a signaling pathway induced by many death stimuli, including tumor necrosis factor alpha, Fas, and the anticancer drugs cisplatin and paclitaxel. Here we report that ASK1 proapoptotic activity is antagonized by association with 14-3-3 proteins. We found that ASK1 specifically bound 14-3-3 proteins via a site involving Ser-967 of ASK1. Interestingly, overexpression of 14-3-3 in HeLa cells blocked ASK1-induced apoptosis whereas disruption of the ASK1/14-3-3 interaction dramatically accelerated ASK1-induced cell death. Targeting of ASK1 by a 14-3-3-mediated survival pathway may provide a novel mechanism for the suppression of apoptosis.


Effectiveness of a 30-min CPR self-instruction program for lay responders: a controlled randomized study.
The length of current 4-h classes in cardiopulmonary resuscitation (CPR) is a barrier to widespread dissemination of CPR training. The effectiveness of video-based self-instruction (VSI) has been demonstrated in several studies; however, the effectiveness of this method with older adults is not certain. Although older adults are most likely to witness out-of-hospital cardiac arrests, these potential rescuers are underrepresented in traditional classes. We evaluated a VSI program that comprised a 22-min video, an inflatable training manikin, and an audio prompting device with individuals 40-70 years old. The hypotheses were that VSI results in performance of basic CPR skills superior to that of untrained learners and similar to that of learners in Heartsaver classes. Two hundred and eighty-five adults between 40 and 70 years old who had had no CPR training within the past 5 years were assigned to an untrained control group, Heartsaver training, or one of three versions of VSI. Basic CPR skills were measured by instructor assessment and by a sensored manikin. The percentage of subjects who assessed unresponsiveness, called the emergency telephone number 911, provided adequate ventilation, proper hand placement, and adequate compression depth was significantly better (P<0.05) for the VSI groups than for untrained controls. VSI subjects tended to have better overall performance and better ventilation performance than did Heartsaver subjects. Older adults learned the fundamental skills of CPR with this training program in about half an hour. If properly distributed, this type of training could produce a significant increase in the number of lay responders who can perform CPR.


Don't tread on me: masculine honor ideology in the U.S. and militant responses to terrorism.
Using both college students and a national sample of adults, the authors report evidence linking the ideology of masculine honor in the U.S. with militant responses to terrorism. In Study 1, individuals' honor ideology endorsement predicted, among other outcomes, open-ended hostile responses to a fictitious attack on the Statue of Liberty and support for the use of extreme counterterrorism measures (e.g., severe interrogations), controlling for right-wing authoritarianism, social dominance orientation, and other covariates. In Study 2, the authors used a regional classification to distinguish honor state respondents from nonhonor state respondents, as has traditionally been done in the literature, and showed that students attending a southwestern university desired the death of the terrorists responsible for 9/11 more than did their northern counterparts. These studies are the first to show that masculine honor ideology in the U.S. has implications for the intergroup phenomenon of people's responses to terrorism.


Beliefs about health, health risks and health expectations from the perspective of people with a psychotic disorder.
To examine beliefs about health, health risks and health expectations from the perspective of people diagnosed with a psychotic disorder. People with psychotic disorders have a threefold higher risk of developing physical health problems than the general population, and prevention of these problems is warranted. Examining patients´ health beliefs could help deepen our understanding of how to plan successful health interventions with this group. Qualitative semi-structured interviews were conducted from November 2010 to October 2011 with 17 people with psychotic disorders. Data were analyzed using a qualitative content analysis. An overall positive picture of health was found despite the fact that physical health was found to be hard to verbalize and understand. Health was mainly associated with psychological wellbeing, while health risks were found to be related to uncertain bodily identity, troublesome thoughts and inner voices, and exclusion from society. Interest in learning, and visions and goals of health seemed to increase awareness of health risks and health expectations, while not worrying could be viewed as a hindrance for health expectations. There is a lack of expressed awareness of physical health risks, but such awareness is fundamental to performing life-style changes [14]. Nurses thus have an important task to help patients understand and verbalize potential physical health risks, and to find out what motivates them to adopt health behaviors.


Native healing traditions must be protected and preserved for future generations.
Toronto physician Mel Borins, who has travelled extensively to developing countries to examine traditional healing practices, recently visited elders at an Ontario Indian reserve to learn more about native healing practices. He is concerned that much native knowledge about the use of herbs and plants for healing will be lost and steps should be taken to protect it. He is also worried about the possible extinction of useful medicinal plants as civilization encroaches on remote areas.


Role of central command in carotid baroreflex resetting in humans during static exercise.
The purpose of the experiments was to examine the role of central command in the exercise-induced resetting of the carotid baroreflex. Eight subjects performed 30 % maximal voluntary contraction (MVC) static knee extension and flexion with manipulation of central command (CC) by patellar tendon vibration (PTV). The same subjects also performed static knee extension and flexion exercise without PTV at a force development that elicited the same ratings of perceived exertion (RPE) as those observed during exercise with PTV in order to assess involvement of the exercise pressor reflex. Carotid baroreflex (CBR) function curves were modelled from the heart rate (HR) and mean arterial pressure (MAP) responses to rapid changes in neck pressure and suction during steady state static exercise. Knee extension exercise with PTV (decreased CC activation) reset the CBR-HR and CBR-MAP to a lower operating pressure (P < 0.05) and knee flexion exercise with PTV (increased CC activation) reset the CBR-HR and CBR-MAP to a higher operating pressure (P < 0.05). Comparison between knee extension and flexion exercise at the same RPE with and without PTV found no difference in the resetting of the CBR-HR function curves (P > 0.05) suggesting the response was determined primarily by CC activation. However, the CBR-MAP function curves were reset to operating pressures determined by both exercise pressor reflex (EPR) and central command activation. Thus the physiological response to exercise requires CC activation to reset the carotid-cardiac reflex but requires either CC or EPR to reset the carotid-vasomotor reflex.


Assessing Late Cardiopulmonary Function in Patients with Repaired Tetralogy of Fallot Using Exercise Cardiopulmonary Function Test and Cardiac Magnetic Resonance.
Patients with repaired tetralogy of Fallot (TOF) usually experience progressive right ventricle (RV) dysfunction due to pulmonary regurgitation (PR). This could further worsen the cardiopulmonary function. This study aimed to compare the changes in patient exercise cardiopulmonary test and cardiac magnetic resonance imaging, and consider the implication of these changes. Our study examined repaired TOF patients who underwent cardiopulmonary exercise test (CPET) to obtain maximal (peak oxygen consumption, peak VO2) and submaximal parameters (oxygen uptake efficiency plateau, oxygen uptake efficiency plateau (OUEP), and ratio of minute ventilation to carbon dioxide production, VE/VCO2 slope). Additionally, the hemodynamic status was assessed by using cardiac magnetic resonance. Criteria for exclusion included TOF patients with pulmonary atresia, atrioventricular septal defect, or absence of pulmonary valve syndrome. We enrolled 158 patients whose mean age at repair was 7.8 ± 9.1 years (range 0.1-49.2 years) and the mean patient age at CPET was 29.5 ± 12.2 years (range 7.0-57.0 years). Severe PR (PR fraction ≥ 40%) in 53 patients, moderate in 55, and mild (PR fraction < 20%) in 50 patients were noted. The mean RV end-diastolic volume index (RVEDVi) was 113 ± 35 ml/m(2), with 7 patients observed to have a RVEDVi > 163 ml/m(2). The mean left ventricular ejection fraction (LVEF) was 63 ± 8%, left ventricular end-diastolic volume index (LVEDVi) was 65 ± 12 ml/m(2), and LVESVi was 25 ± 14 ml/m(2). CPET revealed significantly decreased peak VO2 (68.5 ± 14.4% of predicted), and fair OUEP (90.3 ± 14.1% of predicted) and VE/VCO2 slope (27.1 ± 5.3). PR fraction and age at repair were negatively correlated with maximal and submaximal exercise indicators (peak VO2 and OUEP). Left ventricular (LV) function and size were positively correlated with peak VO2 and OUEP. The results of CPET showed that patients with repaired TOF had a low maximal exercise capacity (peak VO2), but a fair submaximal exercise capacity (OUEP and VE/VCO2 slope), suggesting limited exercise capability in high intensity circumstances. PR, LV function and age at total repair were the most important determinants of CPET performance. Cardiac magnetic resonance; Cardiopulmonary exercise function; Pulmonary regurgitation; Surgical age; Tetralogy of Fallot.


Characteristics of Foreign-Born Persons in the Swiss Hepatitis C Cohort Study: Implications for Screening Recommendations.
Switzerland recommends individuals who originate from high-prevalence countries to be screened for hepatitis C virus (HCV) infection. However, not all these persons are equally at risk. We thus aimed to describe the number and characteristics of persons with HCV infection born outside of Switzerland. We compared characteristics of anti-HCV-positive individuals in the Swiss Hepatitis C Cohort Study (SCCS) and of HCV cases reported to the Federal Office of Public Health (FOPH), with those of the general population in Switzerland. Persons who inject drugs (PWID) and persons who do not inject drugs (non-PWID) were compared by age groups for different countries of origin (represented by ≥1% of participants in the SCCS or FOPH). We included 4,199 persons from the SCCS and 26,610 cases from the FOPH. Both groups had similar characteristics. In both data sources non-PWID were more frequent in foreign-born than in Swiss-born persons (63% versus 34% in the SCCS). The only subgroup with a clearly higher proportion both in the SCCS and FOPH than in the general population were persons over 60 years from Italy and Spain, with a 3.7- and 2.8-fold increase in the SCCS. These persons were non-PWID (99%), less frequently HIV- and anti-HBc positive and more often female than PWID from Italy and Spain; cirrhosis at enrolment was frequent (31%). Their HCV genotypes were consistent with those observed in elderly non-PWID of their birth countries. In the FOPH a higher proportion than in the general population was also seen for cases from Georgia and Russia. The identification of subgroups in which HCV infection is particularly frequent might allow for better targeting HCV screening among foreign-born persons in Switzerland and elsewhere.


Influence of Pleurectomy and Decortication in Health-Related Quality of Life Among Patients with Malignant Pleural Mesothelioma.
Complete macroscopic resection surgery, pleurectomy and decortication (PD) improve survival in selected patients with malignant pleural mesothelioma (MPM). Yet its value has been questioned because of concern that this extensive surgical procedure may disrupt health-related quality of life (HRQoL). HRQoL was studied in patients undergoing PD surgery for MPM using EORTC QLQ-C30 instrument at baseline (prior to surgery), 1, 4-5, 7-8, and 10-11 months following surgery. Global health and variables in function and symptom domains were investigated. Sub-groups analyses were performed for ECOG performance status (PS), histological sub-types and pathological tumor volume (pTV). Within-patient comparisons to baseline scores were made using Wilcoxon signed-rank test. Trends over time were evaluated using Cuzick's nonparametric test. There were 114 patients with median age of 70 years (range: 50-88) and PS 0: 35 (30.7%), epithelioid histology: 61 (53.5%) and volume <600 ml: 58 (50.9%). Patients with good PS (PS 0), epithelioid histology and small pTV had greater level of functioning and were less symptomatic at baseline. Overall global health worsened at the first postoperative month (p = 0.0005) with subsequent improvement. Non-epithelioid histology and patients with large pTV demonstrated greater improvement in global health, function and symptoms domains following a PD. At baseline, the overall health-related quality of life, function and symptom domains were adversely affected in non-epithelioid histology and patients with large pTV. However, greatest improvement in global health, symptom and function domains were observed first month after PD and during the follow-up in these sub-groups.


Revealing the structure of a catalytic combustion active-site ensemble combining uniform nanocrystal catalysts and theory insights.
Supported metal catalysts are extensively used in industrial and environmental applications. To improve their performance, it is crucial to identify the most active sites. This identification is, however, made challenging by the presence of a large number of potential surface structures that complicate such an assignment. Often, the active site is formed by an ensemble of atoms, thus introducing further complications in its identification. Being able to produce uniform structures and identify the ones that are responsible for the catalyst performance is a crucial goal. In this work, we utilize a combination of uniform Pd/Pt nanocrystal catalysts and theory to reveal the catalytic active-site ensemble in highly active propene combustion materials. Using colloidal chemistry to exquisitely control nanoparticle size, we find that intrinsic rates for propene combustion in the presence of water increase monotonically with particle size on Pt-rich catalysts, suggesting that the reaction is structure dependent. We also reveal that water has a near-zero or mildly positive reaction rate order over Pd/Pt catalysts. Theory insights allow us to determine that the interaction of water with extended terraces present in large particles leads to the formation of step sites on metallic surfaces. These specific step-edge sites are responsible for the efficient combustion of propene at low temperature. This work reveals an elusive geometric ensemble, thus clearly identifying the active site in alkene combustion catalysts. These insights demonstrate how the combination of uniform catalysts and theory can provide a much deeper understanding of active-site geometry for many applications.


NCCN Task Force report: management of patients with gastrointestinal stromal tumor (GIST)--update of the NCCN clinical practice guidelines.
The NCCN Soft Tissue Sarcoma Guidelines include a subsection about treatment recommendations for gastrointestinal stromal tumors (GISTs). The standard of practice rapidly changed after the introduction of effective molecularly targeted therapy (such as imatinib and sunitinib) for GIST. Because of these changes, NCCN organized a multidisciplinary panel composed of experts in the fields of medical oncology, molecular diagnostics, pathology, radiation oncology, and surgery to discuss the optimal approach for the care of patients with GIST at all stages of the disease. The GIST Task Force is composed of NCCN faculty and other key experts from the United States, Europe, and Australia. The Task Force met for the first time in October 2003 and again in December 2006 with the purpose of expanding on the existing NCCN guidelines for gastrointestinal sarcomas and identifying areas of future research to optimize our understanding and treatment of GIST.


Complete small subunit rRNA gene sequence of the scuticociliate Miamiensis avidus pathogenic to olive flounder Paralichthys olivaceus.
Eight isolates of Miamiensis avidus (scuticociliates) were collected from olive flounder Paralichthys olivaceus with symptoms of severe ulcers and haemorrhages at several culture farms in 1999 and 2003. Cloned strains were produced and the complete small subunit ribosomal RNA gene (SSU rRNA) of each strain was sequenced for classification and phylogenic study. The SSU rRNA is 1759 bp in length and the sequence was deposited in the GenBank under accession number AY550080. All 8 strains exhibited the same sequence, but this sequence did not match any previously deposited scuticociliate SSU rRNA sequence. Phylogenetic analysis placed Miamiensis avidus in a sister lineage to Cohnilembus verminus, Pseudocohnilembus hargisi and P. marinus.


mCPP-induced hyperactivity in 5-HT2C receptor mutant mice is mediated by activation of multiple 5-HT receptor subtypes.
The serotonin receptor agonist mCPP induces hyperlocomotion in 5-HT2C receptor knockout (KO) mice or in the presence of a 5-HT2C receptor antagonist. In the present group of experiments, we evaluate the role of 5-HT1A, 5-HT1B and 5-HT2A receptors in mCPP-induced hyperactivity in 5-HT2C KO mice. We also assess the ability of agonists at these receptors to induce hyperactivity in wildtype (WT) mice pre-treated with a selective 5-HT2C receptor antagonist. As previously reported, mCPP (3 mg/kg) induced hyperactivity in 5-HT2C KO mice. A combination of the 5-HT1B receptor agonist CP-94,253 (20 mg/kg) and the 5-HT1A receptor agonist 8-OH-DPAT (0.5 mg/kg) induced marked hyperactivity in WT but not in 5-HT2C KO mice, nor in mice treated with the selective 5-HT2C receptor antagonist, SB 242084 (1.5 mg/kg). Neither CP-94,253 nor 8-OH-DPAT had any intrinsic effect on locomotion in WTs. mCPP-induced hyperactivity was attenuated in 5-HT2C KO mice by the 5-HT1B receptor antagonist SB 224289 (2.5 mg/kg), and the 5-HT2A receptor antagonists ketanserin (0.3 mg/kg) and M100907 (0.01 mg/kg) but not by the 5-HT1A receptor antagonist WAY 100635 (1 mg/kg). The 5-HT(2A/2B/2C) receptor agonist, Ro 60-0175 (3 mg/kg), induced a modest increase in locomotor activity in WT mice pre-treated with SB 242084. However, the combination of Ro 60-0175 with CP-94,253 induced a substantial increase in activity in 5-HT2C KO mice, an effect comparable to mCPP-induced hyperactivity. Thus, joint activation of 5-HT1A and 5-HT1B receptors stimulates locomotion in WT mice but this response is dependent on a functional 5-HT2C receptor population and hence is absent in 5-HT2C KO mice. By contrast, mCPP-induced hyperactivity depends on the inactivation of a separate 5-HT2C receptor population and is mediated by 5-HT2A and 5-HT1B receptor activation.


Plasma S-adenosylmethionine, DNMT polymorphisms, and peripheral blood LINE-1 methylation among healthy Chinese adults in Singapore.
Global hypomethylation of repetitive DNA sequences is believed to occur early in tumorigenesis. There is a great interest in identifying factors that contribute to global DNA hypomethylation and associated cancer risk. We tested the hypothesis that plasma S-adenosylmethionine (SAM) level alone or in combination with genetic variation in DNA methyltransferases (DNMT1, DNMT3A and DNMT3B) was associated with global DNA methylation extent at long interspersed nucleotide element-1 (LINE-1) sequences. Plasma SAM level and LINE-1 DNA methylation index were measured using stored blood samples collected from 440 healthy Singaporean Chinese adults during 1994-1999. Genetic polymorphisms of 13 loci in DNMT1, DNMT3A and DNMT3B were determined. LINE-1 methylation index was significantly higher in men than in women (p = 0.001). LINE-1 methylation index was positively associated with plasma SAM levels (p ≤ 0.01), with a plateau at approximately 78% of LINE-1 methylation index (55 nmol/L plasma SAM) in men and 77% methylation index (50 nmol/L plasma SAM) in women. In men only, the T allele of DNMT1 rs21124724 was associated with a statistically significantly higher LINE-1 methylation index (ptrend = 0.001). The DNMT1 rs2114724 genotype modified the association between plasma SAM and LINE-1 methylation index at low levels of plasma SAM in men. Circulating SAM level was associated with LINE-1 methylation status among healthy Chinese adults. The DNMT1 genetic polymorphism may exert a modifying effect on the association between SAM and LINE-1 methylation status in men, especially when plasma SAM level is low. Our findings support a link between plasma SAM and global DNA methylation status at LINE-1 sequences.


Interview with robert g. Shulman.
Robert G. Shulman is the Sterling Professor of Molecular Biophysics and Biochemistry at Yale University. He received his B.A. and Ph.D. degrees at Columbia in physical chemistry, with an intervening period as Lt(jg) USNR. Soon after graduate studies with C. H. Townes in microwave spectroscopy, he went to Bell Telephone Laboratories, where he started Nuclear Magnetic Resonance research on antiferromagnetics; superconductors; semiconductors; and, eventually, biomolecules. A year working with F. H. C. Crick and S. Brenner on phage genetics solidified his interest in biophysics. He started and led biophysics research at Bell Labs, where he studied a variety of biomolecules by NMR. This led him to in vivo NMR, at first in microorganisms; then animals; and, finally, humans. Since 1979 he has been at Yale University, where he has been following metabolism in vivo by magnetic resonance in brain and muscle measuring changes during activation. He is a member of the National Academy of Sciences and Institute of Medicine.


Gapless genome assembly of Colletotrichum higginsianum reveals chromosome structure and association of transposable elements with secondary metabolite gene clusters.
The ascomycete fungus Colletotrichum higginsianum causes anthracnose disease of brassica crops and the model plant Arabidopsis thaliana. Previous versions of the genome sequence were highly fragmented, causing errors in the prediction of protein-coding genes and preventing the analysis of repetitive sequences and genome architecture. Here, we re-sequenced the genome using single-molecule real-time (SMRT) sequencing technology and, in combination with optical map data, this provided a gapless assembly of all twelve chromosomes except for the ribosomal DNA repeat cluster on chromosome 7. The more accurate gene annotation made possible by this new assembly revealed a large repertoire of secondary metabolism (SM) key genes (89) and putative biosynthetic pathways (77 SM gene clusters). The two mini-chromosomes differed from the ten core chromosomes in being repeat- and AT-rich and gene-poor but were significantly enriched with genes encoding putative secreted effector proteins. Transposable elements (TEs) were found to occupy 7% of the genome by length. Certain TE families showed a statistically significant association with effector genes and SM cluster genes and were transcriptionally active at particular stages of fungal development. All 24 subtelomeres were found to contain one of three highly-conserved repeat elements which, by providing sites for homologous recombination, were probably instrumental in four segmental duplications. The gapless genome of C. higginsianum provides access to repeat-rich regions that were previously poorly assembled, notably the mini-chromosomes and subtelomeres, and allowed prediction of the complete SM gene repertoire. It also provides insights into the potential role of TEs in gene and genome evolution and host adaptation in this asexual pathogen.


Diffusion maximum as a function of size in dense liquids.
We study the diffusion of small guest particles of different sizes in a host fluid at liquid densities using molecular dynamics simulations. We observe an enhancement of the diffusivity of guest particles for a size related to the structure of the void space of the host fluid, analogous to the "levitation effect" observed for guest diffusion in porous solids. Friction and activation energy are found to be minimum for the guest size with maximum self-diffusivity. Wavelength dependent self-diffusivity indicates a monotonic and oscillatory dependence on wave number k for anomalous and linear regimes, respectively. These are associated with single and bi-exponential decay of the incoherent intermediate scattering function.


Sedimentation equilibrium of a small oligomer-forming membrane protein: effect of histidine protonation on pentameric stability.
Analytical ultracentrifugation (AUC) can be used to study reversible interactions between macromolecules over a wide range of interaction strengths and under physiological conditions. This makes AUC a method of choice to quantitatively assess stoichiometry and thermodynamics of homo- and hetero-association that are transient and reversible in biochemical processes. In the modality of sedimentation equilibrium (SE), a balance between diffusion and sedimentation provides a profile as a function of radial distance that depends on a specific association model. Herein, a detailed SE protocol is described to determine the size and monomer-monomer association energy of a small membrane protein oligomer using an analytical ultracentrifuge. AUC-ES is label-free, only based on physical principles, and can be used on both water soluble and membrane proteins. An example is shown of the latter, the small hydrophobic (SH) protein in the human respiratory syncytial virus (hRSV), a 65-amino acid polypeptide with a single α-helical transmembrane (TM) domain that forms pentameric ion channels. NMR-based structural data shows that SH protein has two protonatable His residues in its transmembrane domain that are oriented facing the lumen of the channel. SE experiments have been designed to determine how pH affects association constant and the oligomeric size of SH protein. While the pentameric form was preserved in all cases, its association constant was reduced at low pH. These data are in agreement with a similar pH dependency observed for SH channel activity, consistent with a lumenal orientation of the two His residues in SH protein. The latter may experience electrostatic repulsion and reduced oligomer stability at low pH. In summary, this method is applicable whenever quantitative information on subtle protein-protein association changes in physiological conditions have to be measured.


Serum and bone concentrations of teicoplanin and vancomycin: study in an animal model.
Teicoplanin and vancomycin are antibiotics widely used in the therapy of bone and joint infections. The aim of this study was to compare bone and serum concentrations of each antibiotic in guinea pigs after administration of 50 mg/kg of teicoplanin or vancomycin by the intravenous route. Serum and bone concentrations were determined immediately before and 0.5, 1, 2, 6, 12 and 24 h after drug administration by means of high performance liquid chromatography. Teicoplanin concentrations were always higher than vancomycin levels. Area under the concentration/time curve was significantly greater for teicoplanin than for vancomycin. In bone, teicoplanin concentration increased up to 6 h, while vancomycin reached its peak after 2 h. Moreover, teicoplanin showed markedly higher levels at 6, 12 and 24 h than vancomycin. In conclusion, the ability of teicoplanin to penetrate bone in greater amount than vancomycin confirms the potential use of teicoplanin in the treatment of bone infections and in the prophylaxis of orthopedic surgery.


Disentangling defects and sound modes in disordered solids.
We develop a new method to isolate localized defects from extended vibrational modes in disordered solids. This method augments particle interactions with an artificial potential that acts as a high-pass filter: it preserves small-scale structures while pushing extended vibrational modes to higher frequencies. The low-frequency modes that remain are "bare" defects; they are exponentially localized without the quadrupolar tails associated with elastic interactions. We demonstrate that these localized excitations are excellent predictors of plastic rearrangements in the solid. We characterize several of the properties of these defects that appear in mesoscopic theory of plasticity, including their distribution of energy barriers, number density, and size, which is a first step in testing and revising continuum models for plasticity in disordered solids.


Nanoarchitectures of the animal extracellular matrix: opportunities for synchrotron radiation studies on collagen and fibrillin.
The extracellular matrix comprises structures that support the architectural organization of virtually all animal tissues. Within this architecture, two classes of protein assemblies found as long slender fibrils (collagen and fibrillin) characterize the bulk of the extracellular matrix. In both classes of fibrous protein, the molecular organization within a fibril ensures that the properties of the individual molecules transcend to the nanostructural and mesoscopic levels of structural organization and thence the tissue itself. The composition of the fibrils, in conjunction with other biomolecules and their suprafibrillar architecture, facilitates the formation of tissues as diverse as skin, tendon, cornea ciliary zonules and aorta. Here the relative tear resistance, strength, transparency and optical properties are paramount for proper function. Many structural investigations of fibrous protein structure have relied heavily on the use of synchrotron radiation in order to elucidate molecular packing, primarily due to the distinct benefits that X-ray diffraction provides, such as minimal sample preparation, rapid data collection and in situ mechanical testing. In this paper, an overview of the investigations that have revealed different levels of molecular architecture in fibril-based tissues is presented. Emerging future technology and how this can be matched with the pressing questions in extracellular matrix biology are also discussed.


Anaplastic myxopapillary ependymoma in an infant: Case report and literature review.
A 7-month-old boy presented with gastrointestinal disturbance, mild neurologic deficit of the left lower extremity and levo-scoliosis of the thoracic spine. Magnetic resonance imaging demonstrated a large intramedullary lesion involving the thoracic spine, from level T1 to T11. Histologic analysis showed a glial tumor with fibrillary processes arranged in radial pattern around mucoid fibrovascular cores with a high proliferative index (focally up to 80%) and prominent vascular endothelial hyperplasia. These findings were consistent with an anaplastic myxopapillary ependymoma. Subtotal resection was performed via a T3-T10 laminoplasty. A ventricular shunt was placed, and the patient subsequently received chemoradiation therapy. To date, this is the second case of a myxopapillary ependymoma with high-grade anaplastic features and the first case in an infant reported in the literature.


Patterns of internationalization and criteria for research assessment in the social sciences and humanities.
This article investigates the developments during the last decades in the use of languages, publication types and publication channels in the social sciences and humanities (SSH). The purpose is to develop an understanding of the processes of internationalization and to apply this understanding in a critical examination of two often used general criteria in research evaluations in the SSH. One of them is that the coverage of a publication in Scopus or Web of Science is seen in itself as an expression of research quality and of internationalization. The other is that a specific international language, English, and a specific type of publication, journal articles, are perceived as supreme in a general hierarchy of languages and publication types. Simple distinctions based on these criteria are contrary to the heterogeneous publication patterns needed in the SSH to organize their research adequately, present their results properly, reach their audiences efficiently, and thereby fulfil their missions. Research quality, internationalization, and societal relevance can be promoted in research assessment in the SSH without categorical hierarchies of publications. I will demonstrate this by using data from scholarly publishing in the SSH that go beyond the coverage in the commercial data sources in order to give a more comprehensive representation of scholarly publishing in the SSH.


A selection index for gene expression evolution and its application to the divergence between humans and chimpanzees.
The importance of gene regulation in animal evolution is a matter of long-standing interest, but measuring the impact of selection on gene expression has proven a challenge. Here, we propose a selection index of gene expression as a straightforward method for assessing the mode and strength of selection operating on gene expression levels. The index is based on the widely used McDonald-Kreitman test and requires the estimation of four quantities: the within-species and between-species expression variances as well as the sequence heterozygosity and divergence of neutrally evolving sequences. We apply the method to data from human and chimpanzee lymphoblastoid cell lines and show that gene expression is in general under strong stabilizing selection. We also demonstrate how the same framework can be used to estimate the proportion of adaptive gene expression evolution.


Mechanical and morphological properties of chronically inactive cat tibialis anterior motor units.
1. The lumbar spinal cord was functionally isolated in ten cats by cord transection at the junctions of segments T12-T13 and L7-S1 and cutting bilaterally all dorsal roots between the two transections. Two 24 h EMG recording sessions were used to verify that muscles in the lower limb were virtually electrically silent. The cats were maintained in excellent health for 6 months. 2. Six months after spinal cord isolation, an acute experiment was performed to isolate a single motor unit from the tibialis anterior of each hindlimb using ventral root splitting techniques. Each motor unit was characterized physiologically as either fast fatigable (FF, n = 11), fast fatigue resistant (FR, n = 4), fast intermediate (FI, n = 2), or slow (S, n = 1), and repetitively stimulated to deplete the motor unit of its glycogen. 3. Maximum tensions of the fast motor units were lower than mean maximum tensions of control, whereas the S motor unit remained within the range observed in controls. In general, the isometric contractile properties, as well as fatigability, were within the ranges for each of the motor unit types in control cats. The mean fibre cross-sectional areas of the fibres within the FR and FF motor units were approximately 40 and 50% smaller than control, while the mean fibre size of the fibers within the S motor unit was similar to control. 4. Innervation ratios and specific tensions for all experimental motor units were within the ranges of those reported for tibialis anterior motor units in control cats. Thus, it appears that the decrease in maximum tension of the fast motor units was primarily related to a reduction in fibre size. 5. The spatial distribution of the fibres within fast motor units of a spinally isolated cat, as measured by interfibre distances of the motor unit fibres, was similar to that reported for control tibialis anterior motor units. 6. These data suggest that factors independent of activity play a prominent, if not dominant, role in maintaining the complement of motor unit types typical of adult cat muscles. In addition, normal innervation patterns appear to be maintained in the absence of activity.


Invasive mucinous carcinoma of the breast and response patterns after neoadjuvant chemotherapy (NAC).
Neoadjuvant chemotherapy (NAC) is often used to treat localised invasive breast cancer. Invasive mucinous carcinoma (IMC) is considered to be an indolent form of invasive breast cancer, and is rarely treated with NAC. We report the largest series of IMCs treated with NAC, and report a characteristic, but not well recognised, pattern of pathological response. Our series included seven patients with IMC treated with NAC. Three patients presented with locally advanced disease, three patients had tumours that were HER-2/neu-positive, and four patients had tumours with admixed mucinous and micropapillary features. Clinical and imaging assessment of response showed persistent and, in some cases, progressive disease, despite evidence of significant pathological response in these cases. Pathological assessment after NAC demonstrated marked reduction in tumour cellularity, but persistent space-occupying mucin pools, showing acellular mucin in one case, <1% tumour cellularity in three cases, and 5-10% cellularity in three cases in both the treated breast and axillary lymph nodes. Persistent mass-forming low-cellular or acellular mucin pools can result in discordant clinical, imaging and pathological findings in IMC treated with NAC.


A new multi-scale method to reveal hierarchical modular structures in biological networks.
Biological networks are effective tools for studying molecular interactions. Modular structure, in which genes or proteins may tend to be associated with functional modules or protein complexes, is a remarkable feature of biological networks. Mining modular structure from biological networks enables us to focus on a set of potentially important nodes, which provides a reliable guide to future biological experiments. The first fundamental challenge in mining modular structure from biological networks is that the quality of the observed network data is usually low owing to noise and incompleteness in the obtained networks. The second problem that poses a challenge to existing approaches to the mining of modular structure is that the organization of both functional modules and protein complexes in networks is far more complicated than was ever thought. For instance, the sizes of different modules vary considerably from each other and they often form multi-scale hierarchical structures. To solve these problems, we propose a new multi-scale protocol for mining modular structure (named ISIMB) driven by a node similarity metric, which works in an iteratively converged space to reduce the effects of the low data quality of the observed network data. The multi-scale node similarity metric couples both the local and the global topology of the network with a resolution regulator. By varying this resolution regulator to give different weightings to the local and global terms in the metric, the ISIMB method is able to fit the shape of modules and to detect them on different scales. Experiments on protein-protein interaction and genetic interaction networks show that our method can not only mine functional modules and protein complexes successfully, but can also predict functional modules from specific to general and reveal the hierarchical organization of protein complexes.


CMP kinase from Escherichia coli is structurally related to other nucleoside monophosphate kinases.
CMP kinase from Escherichia coli is a monomeric protein of 225 amino acid residues. The protein exhibits little overall sequence similarities with other known NMP kinases. However, residues involved in binding of substrates and/or in catalysis were found conserved, and sequence comparison suggested conservation of the global fold found in adenylate kinases or in several CMP/UMP kinases. The enzyme was purified to homogeneity, crystallized, and analyzed for its structural and catalytic properties. The crystals belong to the hexagonal space group P6(3), have unit cell parameters a = b = 82.3 A and c = 60.7 A, and diffract x-rays to a 1.9 A resolution. The bacterial enzyme exhibits a fluorescence emission spectrum with maximum at 328 nm upon excitation at 295 nm, which suggests that the single tryptophan residue (Trp30) is located in a hydrophobic environment. Substrate specificity studies showed that CMP kinase from E. coli is active with ATP, dATP, or GTP as donors and with CMP, dCMP, and arabinofuranosyl-CMP as acceptors. This is in contrast with CMP/UMP kinase from Dictyostelium discoideum, an enzyme active on CMP or UMP but much less active on the corresponding deoxynucleotides. Binding of CMP enhanced the affinity of E. coli CMP kinase for ATP or ADP, a particularity never described in this family of proteins that might explain inhibition of enzyme activity by excess of nucleoside monophosphate.


Extended-Release Naltrexone Improves Viral Suppression Among Incarcerated Persons Living With HIV With Opioid Use Disorders Transitioning to the Community: Results of a Double-Blind, Placebo-Controlled Randomized Trial.
To determine whether extended-release naltrexone (XR-NTX) would improve or maintain viral suppression (VS) among prisoners or jail detainees with HIV and opioid use disorder (OUD) transitioning to the community. A 4-site, prospective randomized double-blind, placebo-controlled trial was conducted among prison and jail inmates with HIV and OUD transitioning to the community from September 2010 through March 2016. Eligible participants (N = 93) were randomized 2:1 to receive 6 monthly injections of XR-NTX (n = 66) or placebo (n = 27) starting at release and observed for 6 months. The primary outcome was the proportion that maintained or improved VS (<50 copies/mL) from baseline to 6 months. Participants allocated to XR-NTX significantly improved to VS (<50 copies/mL) from baseline (37.9%) to 6 months (60.6%) (P = 0.002), whereas the placebo group did not (55.6% at baseline to 40.7% at 6 months P = 0.294). There was, however, no statistical significant difference in VS levels at 6 months between XR-NTX (60.6%) vs. placebo (40.7%) (P = 0.087). After controlling for other factors, only allocation to XR-NTX (adjusted odds ratio = 2.90; 95% confidence interval = 1.04 to 8.14, P = 0.043) was associated with the primary outcome. Trajectories in VS from baseline to 6 months differed significantly (P = 0.017) between treatment groups, and the differences in the discordant values were significantly different as well (P = 0.041): the XR-NTX group was more likely than the placebo group to improve VS (30.3% vs. 18.5%), maintain VS (30.3% vs. 27.3), and less likely to lose VS (7.6% vs. 33.3%) by 6 months. XR-NTX improves or maintains VS after release to the community for incarcerated people living with HIV with OUD.


The Values by Nicholas Markell.
Recognizing the contribution art has had in the Mayo Clinic environment since the original Mayo Clinic Building was finished in 1914, Mayo Clinic Proceedings features some of the numerous works of art displayed throughout the buildings and grounds on Mayo Clinic campuses as interpreted by the author.


Electronic doors to education: study of high school website accessibility in Iowa.
The Americans with Disabilities Act (ADA), and Sections 504 and 508 of the Rehabilitation Act, prohibit discrimination against people with disabilities in all aspects of daily life, including education, work, and access to places of public accommodations. Increasingly, these antidiscrimination laws are used by persons with disabilities to ensure equal access to e-commerce, and to private and public Internet websites. To help assess the impact of the anti-discrimination mandate for educational communities, this study examined 157 website home pages of Iowa public high schools (52% of high schools in Iowa) in terms of their electronic accessibility for persons with disabilities. We predicted that accessibility problems would limit students and others in obtaining information from the web pages as well as limiting ability to navigate to other web pages. Findings show that although many web pages examined included information in accessible formats, none of the home pages met World Wide Web Consortium (W3C) standards for accessibility. The most frequent accessibility problem was lack of alternative text (ALT tags) for graphics. Technical sophistication built into pages was found to reduce accessibility. Implications are discussed for schools and educational institutions, and for laws, policies, and procedures on website accessibility.


35Year Research History of Cytotoxicity and Cancer: a Quantitative and Qualitative Analysis.
Cancer is the leading cause of morbidity and mortality worldwide, characterized by irregular cell growth. Cytotoxicity or killing tumor cells that divide rapidly is the basic function of chemotherapeutic drugs. However, these agents can damage normal dividing cells, leading to adverse effects in the body. In view of great advances in cancer therapy, which are increasingly reported each year, we quantitatively and qualitatively evaluated the papers published between 1981 and December 2015, with a closer look at the highly cited papers (HCPs), for a better understanding of literature related to cytotoxicity in cancer therapy. Online documents in the Web of Science (WOS) database were analyzed based on the publication year, the number of times they were cited, research area, source, language, document type, countries, organizationenhanced and funding agencies. A total of 3,473 publications relevant to the target key words were found in the WOS database over 35 years and 86% of them (n=2,993) were published between 20002015. These papers had been cited 54,330 times without self citation from 1981 to 2015. Of the 3,473 publications, 17 (3,557citations) were the most frequently cited ones between 2005 and 2015. The topmost HCP was about generating a comprehensive preclinical database (CCLE) with 825 (23.2%) citations. One third of the remaining HCPs had focused on drug discovery through improving conventional therapeutic agents such as metformin and ginseng. Another 33% of the HCPs concerned engineered nanoparticles (NPs) such as polyamidoamine (PAMAM) dendritic polymers, PTX/SPIOloaded PLGAs and cell derived NPs to increase drug effectiveness and decrease drug toxicity in cancer therapy. The remaining HCPs reported novel factors such as miR205, Nrf2 and p27 suggesting their interference with development of cancer in targeted cancer therapy. In conclusion, analysis of 35year publications and HCPs on cytotoxicity in cancer in the present report provides opportunities for a better understanding the extent of topics published and may help future research in this area.


Clinical decision guidelines for NHS cosmetic surgery: analysis of current limitations and recommendations for future development.
Because of increasing demand for publicly funded elective cosmetic surgery, clinical decision guidelines have been developed to select those patients who should receive it. The aims of this study were to identify: the main characteristics of such guidelines; whether and how they influence clinical decision making; and ways in which they should be improved. UK health authorities were asked for their current guidelines for elective cosmetic surgery and, in a single plastic surgery unit, we examined the impact of its guidelines by observing consultations and interviewing surgeons and managers. Of 115 authorities approached, 32 reported using guidelines and provided sufficient information for analysis. Guidelines mostly concerned arbitrary sets of cosmetic procedures and lacked reference to an evidence base. They allowed surgery for specified anatomical, functional or symptomatic reasons, but these indications varied between guidelines. Most guidelines also permitted surgery 'exceptionally' for psychological reasons. The guidelines that were studied in detail did not appreciably influence surgeons' decisions, which reflected criteria that were not cited in the guidelines, including cost of the procedure and whether patients sought restoration or improvement of their appearance. Decision guidelines in this area have several limitations. Future guidelines should: include all cosmetic procedures; be informed by a broad range of evidence; and, arguably, include several nonclinical criteria that currently inform surgeons' decision-making.


Boosting beauty in an economic decline: mating, spending, and the lipstick effect.
Although consumer spending typically declines in economic recessions, some observers have noted that recessions appear to increase women's spending on beauty products--the so-called lipstick effect. Using both historical spending data and rigorous experiments, the authors examine how and why economic recessions influence women's consumer behavior. Findings revealed that recessionary cues--whether naturally occurring or experimentally primed--decreased desire for most products (e.g., electronics, household items). However, these cues consistently increased women's desire for products that increase attractiveness to mates--the first experimental demonstration of the lipstick effect. Additional studies show that this effect is driven by women's desire to attract mates with resources and depends on the perceived mate attraction function served by these products. In addition to showing how and why economic recessions influence women's desire for beauty products, this research provides novel insights into women's mating psychology, consumer behavior, and the relationship between the two.


Effect of a tart cherry juice blend on exercise-induced muscle damage in horses.
To evaluate whether administering a tart cherry juice blend (TCJB) prior to exercise would reduce skeletal and cardiac muscle damage by decreasing the inflammatory and oxidative stress response to exercise in horses. 6 horses. Horses were randomly allocated into 2 groups in a crossover study with a 2-week washout period and orally administered either TCJB or a placebo solution (1.42 L, twice daily) in a double-masked protocol for 2 weeks prior to a stepwise incremental exercise protocol. Horses were tested for serum activities of creatine kinase and aspartate aminotransferase (AST) and concentrations of cardiac troponin I (cTnI), thiobarbituric acid reactive substances (TBARS; an indicator of oxidative stress), and serum amyloid A (SAA; an indicator of inflammation). To ensure that treatment would not result in positive results of an equine drug-screening protocol, serum samples obtained from each horse prior to and after 2 weeks of administration of TCJB or the placebo solution were tested. All horses had negative results of drug screening at both sample times. The exercise protocol resulted in a significant increase in TBARS concentration, SAA concentration, and serum AST activity in all horses. Administration of TCJB or placebo solution was not associated with an effect on malondialdehyde or SAA concentrations. However, administration of TCJB was associated with less serum activity of AST, compared with administration of placebo solution. Administration of TCJB may diminish muscle damage induced by exercise.


[Nationwide surveillance of parenteral antibiotics containing meropenem activities against clinically isolated strains in 2004].
The antibacterial activity of meropenem (MEPM) and other parenteral antibiotics against clinical isolates of 907 strains of Gram-positive bacteria, 1790 strains of Gram-negative bacteria, and 192 strains of anaerobic bacteria obtained from 30 medical institutions during 2004 was measured. The results were as follows; 1. MIC90 of MEPM for almost all of enterobacteriaceae and Haemophilus influenzae were 4-fold to 32-fold lower than those of other carbapenems. MEPM was more active than other carbapenem antibiotics against Gram-negative bacteria, especially against enterobacteriaceae and H. influenzae. MEPM were active against most of the species tested in Gram-positive and anaerobic bacteria, except for multi-drug resistant strains including methicillin-resistant Staphylococcus aureus. 2. As for Pseudomonas aeruginosa, imipenem (IPM) showed high cross-resistant rate againt meropenem-resistant P. aeruginosa (87.9%). MEPM showed low cross-resistant rate both againt IPM-resistant P. aeruginosa (49.2%) and ciprofloxacin-resistant P. aeruginosa (38.0%). 3. The proportion of extended-spectrum beta-lactamase (ESBL) strains was 3.1% (4 strains) in Escherichia coli, 8.0% (2 strains) in Citrobacter koseri, 2.5% (3 strains) in Klebsiella pneumoniae, 2.5% (2 strains) in Enterobacter cloacae, 0.9% (1 strains) in Serratia marcescens, and 2.2% (2 strains) in Proteus mirabilis. The proportion of metallo-beta-lactamase strains was 1.6% (5 strains) in P. aeruginosa. 4. Of all species tested, Peptostreptococcus spp. was the only species, which MIC90 of MEPM was more than 4-fold higher than that in our previous study using clinical isolates during 2002 (0.25 microg/ml --> 1 microg/ml). Therefore, there is almost no siginificant decrease in susceptibility of clinical isolates to meropenem. In conclusion, the results from this surveillance study suggest that MEPM retains its potent and broad antibacterial activity and therefore is a clinically useful carbapenem at present, 9 years after available for commercial use.


Psychoneuroendocrine interventions aimed at attenuating immunosenescence: a review.
There is evidence suggesting that immunosenescence can be accelerated by external factors such as chronic stress. Here we review potential psychoneuroendocrine determinants of premature aging of the immune system and discuss available interventions aimed at attenuating immunosenescence. Chronic stress may accelerate various features of immunosenescence by activating key allostatic systems, notably the hypothalamic-pituitary-adrenal axis. The immunological impact of such neuroendocrine dysregulation may be further amplified by a dramatic decline in dehydroepiandrosterone (DHEA) levels, acting in part as an endogenous glucocorticoid antagonist. Stress-buffering strategies show beneficial effects on various biomarkers in elderly populations. Likewise, supplementation of DHEA, melatonin or growth hormone has yielded significant beneficial effects in a number of studies, including: increased well-being, memory performance, bone mineral density and improved immunocompetence as evidenced by results of in vitro (T cell proliferation, cytotoxicity, cytokine production), and in vivo immune challenges. However, the side-effects of hormonal supplementation are also discussed. Finally, moderate exercise via the promotion of cortisol/DHEA balance or epigenetic modifications, is associated with lower serum pro-inflammatory cytokines, greater lymphoproliferative responses and lower counts of senescent T cells. Taken together, these data suggest that immune system is plastic and immunosenescence can be attenuated psychoneuroendocrine interventions.


Cry1F resistance among lepidopteran pests: a model for improved resistance management?
The Cry1Fa protein from the bacterium Bacillus thuringiensis (Bt) is known for its potential to control lepidopteran pests, especially through transgenic expression in maize and cotton. The maize event TC1507 expressing the cry1Fa toxin gene became commercially available in the United States in 2003 for the management of key lepidopteran pests including the European corn borer, Ostrinia nubilalis, and the fall armyworm, Spodoptera frugiperda. A high-dose/refuge strategy has been widely adopted to delay evolution of resistance to event TC1507 and other transgenic Bt crops. Efficacy of this strategy depends on the crops expressing a high dose of the Bt toxin to targeted pests and adjacent refuges of non-Bt host plants serving as a source of abundant susceptible insects. While this strategy has proved effective in delaying O. nubilalis resistance, field-evolved resistance to event TC1507 has been reported in S. frugiperda populations in Puerto Rico, Brazil, and the southeastern United States. This paper examines available information on resistance to Cry1Fa in O. nubilalis and S. frugiperda and discusses how this information identifies opportunities to refine resistance management recommendations for Bt maize.


Cytoplasmic trafficking of minute virus of mice: low-pH requirement, routing to late endosomes, and proteasome interaction.
The cytoplasmic trafficking of the prototype strain of minute virus of mice (MVMp) was investigated by analyzing and quantifying the effect of drugs that reduce or abolish specific cellular functions on the accumulation of viral macromolecules. With this strategy, it was found that a low endosomal pH is required for the infection, since bafilomycin A(1) and chloroquine, two pH-interfering drugs, were similarly active against MVMp. Disruption of the endosomal network by brefeldin A interfered with MVMp infection, indicating that viral particles are routed farther than the early endocytic compartment. Pulse experiments with endosome-interfering drugs showed that the bulk of MVMp particles remained in the endosomal compartment for several hours before its release to the cytosol. Drugs that block the activity of the proteasome by different mechanisms, such as MG132, lactacystin, and epoxomicin, all strongly blocked MVMp infection. Pulse experiments with the proteasome inhibitor MG132 indicated that MVMp interacts with cellular proteasomes after endosomal escape. The chymotrypsin-like but not the trypsin-like activity of the proteasome is required for the infection, since the chymotrypsin inhibitors N-tosyl-L-phenylalanine chloromethyl ketone and aclarubicin were both effective in blocking MVMp infection. However, the trypsin inhibitor Nalpha-p-tosyl-L-lysine chloromethyl ketone had no effect. These results suggest that the ubiquitin-proteasome pathway plays an essential role in the MVMp life cycle, probably assisting at the stages of capsid disassembly and/or nuclear translocation.


Transmission bows of radially inhomogeneous spheres.
We consider transmission scattering of a plane wave by a radially inhomogeneous sphere containing a localized region of refractive index decrease. In ray theory, the boundary conditions on the deflection angle at axial and grazing incidence determine that transmission scattering gives rise to an even number of bows, half of them being relative maximum bows and half being relative minimum bows. For a model refractive index profile, we determine the conditions under which different numbers of bows occur, and we suggest physical mechanisms responsible for producing them. We also verify that these bows occur in wave scattering in the short wavelength limit, both in the frequency domain and time domain.


A Phase Ib/II Study of Pepinemab in Combination with Avelumab in Advanced Non-Small Cell Lung Cancer.
The CLASSICAL-Lung clinical trial tested the combination of pepinemab, an IgG4 humanized mAb targeting semaphorin 4D, with the PD-L1 inhibitor avelumab to assess the effects of coupling increased T-cell infiltration and reversal of immune suppression via pepinemab with sustained T-cell activation via checkpoint inhibition. This phase Ib/II, single-arm study was designed to evaluate the safety, tolerability, and efficacy of pepinemab in combination with avelumab in 62 patients with advanced non-small cell lung cancer (NSCLC), including immunotherapy-naïve (ION) patients and patients whose tumors progressed following anti-PD-1/L1 monotherapy (IOF). The main objectives were to evaluate safety/tolerability, establish a recommended phase 2 dose (RP2D), obtain a preliminary evaluation of antitumor activity, and investigate candidate biomarker activity. The combination was well tolerated with no major safety signals identified. Pepinemab, 10 mg/kg with avelumab, 10 mg/kg, every 2 weeks, was selected as the RP2D. Among 21 evaluable ION patients, 5 patients experienced partial responses (PR), 4 patients evidenced clinical benefit ≥1 year, and the disease control rate (DCR) was 81%. Notably, overall response rate with the combination therapy was higher than previously reported for single-agent avelumab in the PD-L1-negative/low population. Among 29 evaluable IOF patients, the combination resulted in a DCR of 59%, including 2 PR and 7 patients with durable clinical benefit of ≥23 weeks. Biomarker analysis of biopsies demonstrated increased CD8 T-cell density correlating with RECIST response criteria. The combination of pepinemab with avelumab was well tolerated in NSCLC and showed signs of antitumor activity in immunotherapy-resistant and PD-L1-negative/low tumors.


Nomograms for predicting changes in semen parameters in infertile men after varicocele repair.
To formulate nomograms based on pre-repair characteristics to predict improvements in semen parameters after varicocele repair. Model using multivariable linear regression based on prospectively collected database, with performance was quantified by concordance correlation coefficient and Pearson correlation coefficient after internal validation with bootstrapping. A male infertility specialty clinic. Men presenting for fertility evaluation from 2003-2012 having varicocele repair. None. Semen parameters before and after varicocele repair. Men undergoing varicocele repair (surgical or embolization) were identified via a prospectively collected database. The relationship of pre-repair semen and clinical characteristics to improvements in semen parameters was modeled using multivariable linear regression, then the model performance was quantified by concordance correlation coefficient and Pearson correlation coefficient after internal validation with bootstrapping. A total of 376 men who had undergone varicocele repair had data available for analysis. After varicocelectomy, the total motile count (TMC) varied depending on the initial left varicocele grade, ejaculate volume, sperm concentration, and motility. The final sperm concentration depended on the initial left varicocele grade, sperm concentration, and motility. The postvaricocelectomy sperm motility varied depending on the patient's age, left varicocele grade, sperm motility, morphology, and TMC. The final percentage of normal forms depended on the prevaricocelectomy sperm morphology, age, right varicocele grade, normal morphology, and TMC. Nomograms using prevaricocelectomy semen parameters and clinical features were developed to predict postvaricocelectomy TMC, sperm concentration, motility, and morphology. The concordance correlation coefficients were 0.45, 0.47, 0.65, and 0.36, respectively. Clinical factors provide substantial ability to predict postvaricocele repair semen parameters. These nomograms may be used by clinicians to predict postvaricocele repair semen parameters.


Structural Differences Between Healthy Subjects and Patients With Schizophrenia or Schizoaffective Disorder: A Graph and Control Theoretical Perspective.
The coordinated dynamic interactions of large-scale brain circuits and networks have been associated with cognitive functions and behavior. Recent advances in network neuroscience have suggested that the anatomical organization of such networks puts fundamental constraints on the dynamical landscape of brain activity, i.e., the different states, or patterns of regional activation, and transition between states the brain can display. Specifically, it has been shown that densely connected, central regions control the transition between states that are "easily" reachable (in terms of expended energy), whereas weakly connected areas control transitions to states that are hard-to-reach. Changes in large-scale brain activity have been hypothesized to underlie many neurological and psychiatric disorders. Evidence has emerged that large-scale dysconnectivity might play a crucial role in the pathophysiology of schizophrenia, especially regarding cognitive symptoms. Therefore, an analysis of graph and control theoretic measures of large-scale brain connectivity in patients offers to give insight into the emergence of cognitive disturbances in the disorder. To investigate these potential differences between patients with schizophrenia (SCZ), patients with schizoaffective disorder (SCZaff) and matched healthy controls (HC), we used structural MRI data to assess the microstructural organization of white matter. We first calculate seven graph measures of integration, segregation, centrality and resilience and test for group differences. Second, we extend our analysis beyond these traditional measures and employ a simplified noise-free linear discrete-time and time-invariant network model to calculate two complementary measures of controllability. Average controllability, which identifies brain areas that can guide brain activity into different, easily reachable states with little input energy and modal controllability, which characterizes regions that can push the brain into difficult-to-reach states, i.e., states that require substantial input energy. We identified differences in standard network and controllability measures for both patient groups compared to HCs. We found a strong reduction of betweenness centrality for both patient groups and a strong reduction in average controllability for the SCZ group again in comparison to the HC group. Our findings of network level deficits might help to explain the many cognitive deficits associated with these disorders.


A review of the growth, and of the carcass and meat quality characteristics of the one-humped camel (Camelus dromedaries).
The dromedary camel is a good source of meat especially in areas where the climate adversely affects the performance of other meat animals. This is because of its unique physiological characteristics, including a great tolerance to high temperatures, solar radiation, water scarcity, rough topography and poor vegetation. The average birth weight of camels is about 35kg, but it varies widely between regions, breeds and within the same breed. The meat producing ability of camels is limited by modest growth rates (500g/day). However, camels are mostly produced under traditional extensive systems on poor levels of nutrition and are mostly slaughtered at older ages after a career in work, racing or milk production. Camels reach live weights of about 650kg at 7-8 years of age, and produce carcass weights ranging from 125 to 400kg with dressing-out percentage values from 55% to 70%. Camel carcasses contain about 57% muscle, 26% bone and 17% fat with fore halves (cranial to rib 13) significantly heavier than the hind halves. Camel lean meat contains about 78% water, 19% protein, 3% fat, and 1.2% ash with a small amount of intramuscular fat, which renders it a healthy food for humans. Camel meat has been described as raspberry red to dark brown in colour and the fat of the camel meat is white. Camel meat is similar in taste and texture to beef. The amino acid and mineral contents of camel meat are often higher than beef, probably due to lower intramuscular fat levels. Recently, camel meat has been processed into burgers, patties, sausages and shawarma to add value. Future research efforts need to focus on exploiting the potential of the camel as a source of meat through multidisplinary research into efficient production systems, and improved meat technology and marketing.


Vitamin D status is associated with physical performance: the results of three independent cohorts.
This study, on the association between vitamin D status and physical performance and its decline, shows that vitamin D status is associated with physical performance in several older age groups. However, vitamin D status does not predict a decline in physical performance in individuals aged 55-65 years. Previous research in the Longitudinal Aging Study Amsterdam (LASA) showed an association of vitamin D status with physical performance and its decline in persons aged 65 years and older. The current study aims to determine these associations in younger individuals and to replicate previous research of LASA. Data from three independent cohorts were used: two cohorts of LASA (LASA-II with measurements in 2002 (n = 707) and 2009 (n = 491), LASA-I-2009 (n = 355)) and the baseline measurement of the B-Vitamins for the Prevention of Osteoporotic Fractures (B-PROOF) study (n = 2,813). Participants performed three tests (walking test, chair stands, and tandem stand; range total score 0-12), except in LASA-II-2002 (only walking and chair stands tests; range total score 0-8). Multiple linear and logistic regression were used to assess whether vitamin D status was associated with total physical performance and its decline, respectively. The mean age of the participants was 60.0 (SD 3.0), 65.9 (2.9), 78.4 (5.3), and 74.4 (6.8) years for LASA-II-2002, LASA-II-2009, LASA-I-2009, and B-PROOF, respectively. Vitamin D status was not predictive of a clinical decline in total physical performance score in the LASA-II-2002 cohort (aged 55-65 years). After adjustment for confounding, participants with serum 25(OH)D < 50 nmol/L scored 0.8 (95 % confidence interval 0.4-1.2), 0.9 (0.3-1.5), 1.5 (0.8-2.3), and 0.6 (0.3-0.9) points lower on total physical performance than participants with serum 25(OH)D ≥ 75 nmol/L. Our study confirmed that serum 25(OH)D is associated with physical performance. However, vitamin D status did not predict a clinical decline in physical performance in individuals aged 55-65 years.


A polymorphism (K121Q) of the human glycoprotein PC-1 gene coding region is strongly associated with insulin resistance.
The genes responsible for insulin resistance are poorly defined. Plasma cell differentiation antigen (PC-1) glycoprotein inhibits insulin receptor signaling and is associated with insulin resistance. We describe here a novel polymorphism in exon 4 of the PC-1 gene (K121Q) and demonstrate that it is strongly associated with insulin resistance in 121 healthy nonobese (BMI <30 kg/m2) nondiabetic (by oral glucose tolerance test [OGTT]) Caucasians from Sicily. Compared with 80 KK subjects, Q allele carriers (n = 41, 39 KQ and 2 QQ) showed higher glucose and insulin levels during OGTT (P < 0.001 by two-way analysis of variance) and insulin resistance by euglycemic clamp (M value = 5.25 +/- 1.38 [n = 24] vs. 6.30 +/- 1.39 mg x kg(-1) x min(-1) [n = 49], P = 0.005). Q carriers had higher risk of being hyperinsulinemic and insulin resistant (odds ratio [CI]: 2.99 [1.28-7.0], P < 0.001). Insulin receptor autophosphorylation was reduced (P < 0.01) in cultured skin fibroblasts from KQ versus KK subjects. Skeletal muscle PC-1 content was not different in 11 KQ versus 32 KK subjects (33 +/- 16.1 vs. 17.5 +/- 15 ng/mg protein, P = 0.3). These results suggest a cause-effect relationship between the Q carrying genotype and the insulin resistance phenotype, and raise the possibility that PC-1 genotyping could identify individuals who are at risk of developing insulin resistance, a condition that predisposes to type 2 diabetes and coronary artery disease.