Apparent motion produces multiple deficits in visually guided smooth pursuit eye movements of monkeys.
We used apparent motion targets to explore how degraded visual motion alters smooth pursuit eye movements. Apparent motion targets consisted of brief stationary flashes with a spatial separation (Deltax), temporal separation (Deltat), and apparent target velocity equal to Deltax/Deltat. Changes in pursuit initiation were readily observed when holding target velocity constant and increasing the flash separation. As flash separation increased, the first deficit observed was an increase in the latency to peak eye acceleration. Also seen was a paradoxical increase in initial eye acceleration. Further increases in the flash separation produced larger increases in latency and resulted in decreased eye acceleration. By varying target velocity, we were able to discern that the visual inputs driving pursuit initiation show both temporal and spatial limits. For target velocities above 4-8 degrees /s, deficits in the initiation of pursuit were seen when Deltax exceeded 0.2-0.5 degrees, even when Deltat was small. For target velocities below 4-8 degrees /s, deficits appeared when Deltat exceeded 32-64 ms, even when Deltax was small. Further experiments were designed to determine whether the spatial limit varied as retinal and extra-retinal factors changed. Varying the initial retinal position of the target for motion at 18 degrees /s revealed that the spatial limit increased as a function of retinal eccentricity. We then employed targets that increased velocity twice, once from fixation and again during pursuit. These experiments revealed that, as expected, the spatial limit is expressed in terms of the flash separation on the retina. The spatial limit is uninfluenced by either eye velocity or the absolute velocity of the target. These experiments also demonstrate that "initiation" deficits can be observed during ongoing pursuit, and are thus not deficits in initiation per se. We conclude that such deficits result from degradation of the retino-centric motion signals that drive pursuit eye acceleration. For large flash separations, we also observed deficits in the maintenance of pursuit: sustained eye velocity failed to match the constant apparent target velocity. Deficits in the maintenance of pursuit depended on both target velocity and Deltat and did not result simply from a failure of degraded image motion signals to drive eye acceleration. We argue that such deficits result from a low gain in the eye velocity memory that normally supports the maintenance of pursuit. This low gain may appear because visual inputs are so degraded that the transition from fixation to tracking is incomplete.


[Rare localisations of endemic Burkitt lymphoma: about 21 cases observed in the Haematology Department of the University Hospital of Yopougon Abidjan].
In this retrospective study, we analysed rare localisations of Burkitt lymphoma observed in the Haematology Department of the University Hospital of Yopougon Abidjan. Over a 10-year study period, we saw 106 patients with Burkitt lymphoma, 21 with unusual localisations. The mean age at onset of symptoms or discovery was 15.48 years, and more patients were female. There were 8 cases of primary Burkitt lymphoma in a rare localisation and 13 cases of unusual localisations of secondary lymphomas. The most frequent of these rare lesions were renal (6), ovarian (4), in peripheral nodes (4), testicular (3), and mammary (3). Still rarer were thyroid, skin, pulmonary, and suprarenal localisations. Clinical manifestations were non-specific and difficult to differentiate from other solid tumours. The CMA protocol produced complete remission in 29% of cases (n=6). Seven patients died. In conclusion, the rare forms of Burkitt lymphoma are non-specific and can be mistaken for other solid tumours. Diagnosis should thus be based on histochemical analysis.


Peptide and steroid regulation of muscle degeneration in an insect.
Two types of cell death occur in the intersegmental muscles of the giant silkmoth Antheraea polyphemus. The first results from a slow atrophy of the fibers, and the second is a rapid, programmed dissolution of the muscle. Both types appear to be mediated by endocrine factors. The slow atrophy is brought about by the decline in the steroid molting hormone 20-hydroxyecdysone and can be prevented with exogenous steroid. The rapid degeneration is triggered by the peptide eclosion hormone, but the sensitivity of the muscle to the peptide depends on the history of exposure of the muscle to 20-hydroxyecdysone.


Autotaxin promotes cancer invasion via the lysophosphatidic acid receptor 4: participation of the cyclic AMP/EPAC/Rac1 signaling pathway in invadopodia formation.
The ability of cancer cells to invade and metastasize is the major cause of death in cancer patients. Autotaxin (ATX) is a secreted lysophospholipase whose level of expression within tumors correlates strongly with their aggressiveness and invasiveness. ATX is the major enzyme involved in the production of lysophosphatidic acid (LPA), a phospholipid that is known to act mostly through its three first characterized receptors (LPA(1), LPA(2), and LPA(3)). Tumor cell invasion across tissue boundaries and metastasis are dependent on the capacity of invasive cancer cells to breach the basement membrane. This process can be initiated by the formation of the actin-rich cell protrusions, invadopodia. In this study, we show that ATX is implicated in the formation of invadopodia in various cancer cells types and this effect is dependent on the production of LPA. We further provide evidence that LPA(4) signaling in fibrosarcoma cells regulates invadopodia formation downstream of ATX, a process mediated through the activation of EPAC by cyclic AMP and subsequent Rac1 activation. Results using LPA(4) shRNA support the requirement of the LPA(4) receptor for cell invasion and in vivo metastasis formation. This work presents evidence that blocking the LPA receptor, LPA(4), in fibrosarcoma cells could provide an additional tool to improve the efficacy of treatment of metastasis in patients. Because LPA receptors and ATX are currently being targeted in preclinical trials, the current findings should stimulate future studies to evaluate the expression pattern and clinical outcome of LPA(4), together with other LPA receptors, in various cancer patients.


Socio-demographic predictors of high support needs in newly diagnosed breast cancer patients.
This study aimed to identify high support needs and their socio-demographic predictors to improve supportive care for newly diagnosed breast cancer patients. A cross-sectional study measured patients' needs and unsatisfied support needs by the supportive care needs survey (SCNS-34), administered after surgery, chemotherapy or radiotherapy. Socio-demographic, disease and treatment characteristics completed data collection. A total of 308 questionnaires were completed with a response rate of 88%. The most frequent support needs (73.3% of patients) related to information and the highest unsatisfied support needs to the management of emotions and daily life (36.3-39.6% of patients). Younger age predicted high and dissatisfied support needs (P < 0.05). Patients born outside Switzerland or with a lower level of education had more needs in daily living and psychological domains (P < 0.05). Being born outside Switzerland also predicted dissatisfaction with information provided. Being parent was a predictor of significant needs in the daily living domain after adjusting for disease and treatment characteristics (P= 0.01). Therefore, information, psychological and daily living support for newly diagnosed breast cancer patients should be strongly reinforced, particularly in patients being born outside Switzerland, those with children or being younger. For the latter, support in sexuality domain should also be emphasised.


Isolation of a bisegmented double-stranded RNA virus from Thirlmere reservoir.
A novel bisegmented double-stranded RNA virus has been isolated from water processed from Thirlmere reservoir. The virus is icosahedral, 58 nm in diam., has a buoyant density of 1.32 g/ml in CsCl, has an S value of 400 and a RNA/protein ratio of 0.087. The two linear segments of RNA have approx. mol. wt. of 2.26 X 10(6) and 2.09 X 10(6). The virus contains six polypeptides. The virus was isolated in Drosophila melanogaster cells and fails to replicate in other insect, amphibian, avian, piscine, mammalian and plant cells tested. The virus is biochemically different from infectious pancreatic necrosis virus (IPNV) and Drosophila X virus (DXV). The virus is also serologically unrelated to IPNV (strain Sp) and another invertebrate pathogenic virus, Tellina virus 1. The virus shares common antigens with DXV but is not completely identical.


Retinol improves in vitro oocyte nuclear maturation under heat stress in heifers.
Heat stress (HS) is especially harmful for bovine ovarian follicle development and oocyte competence. Furthermore, HS causes premature aging in oocytes due to high levels of reactive oxygen species (ROS), involved in the harmful effects over the oocyte maturation and the steroidogenic activity of follicular cells. In this study, the presumptive protective effects of antioxidant agents on heat-stressed oocytes were evaluated. Heifer oocytes were matured for 22 h under control (38°C) and HS conditions (41.5°C at 18-21 h of maturation). For each oocyte, nuclear stage and cortical granule (CG) distribution were evaluated. Steroidogenic activity of cumulus cells was also recorded. The antioxidant agents used in the study were: retinol (1.43 μg/ml), retinyl (0.28 μg/ml) and oleic acid (0.05 mg/ml). Based on a chi-squared test (P < 0.05), HS affected negatively the metaphase II (MII) progression and produced a premature CG exocytosis. Retinol improved the oocyte MII progression. However, retinyl and oleic acid, at the concentrations used in this study, could not counteract adverse effects of HS. A decrease in progesterone and increase in estradiol availability were observed when retinyl and oleic acid were supplemented to the maturation medium, respectively. In conclusion, retinol proved to be valuable in heat-stressed oocytes protecting nuclear maturation.


Breakdown of coevolution between symbiotic bacteria Wolbachia and their filarial hosts.
Wolbachia is an alpha-proteobacterial symbiont widely distributed in arthropods. Since the identification of Wolbachia in certain animal-parasitic nematodes (the Onchocercidae or filariae), the relationship between arthropod and nematode Wolbachia has attracted great interest. The obligate symbiosis in filariae, which renders infected species susceptible to antibiotic chemotherapy, was held to be distinct from the Wolbachia-arthropod relationship, typified by reproductive parasitism. While co-evolutionary signatures in Wolbachia-arthropod symbioses are generally weak, reflecting horizontal transmission events, strict co-evolution between filariae and Wolbachia has been reported previously. However, the absence of close outgroups for phylogenetic studies prevented the determination of which host group originally acquired Wolbachia. Here, we present the largest co-phylogenetic analysis of Wolbachia in filariae performed to date including: (i) a screening and an updated phylogeny of Wolbachia; (ii) a co-phylogenetic analysis; and (iii) a hypothesis on the acquisition of Wolbachia infection. First, our results show a general overestimation of Wolbachia occurrence and support the hypothesis of an ancestral absence of infection in the nematode phylum. The accuracy of supergroup J is also underlined. Second, although a global pattern of coevolution remains, the signal is derived predominantly from filarial clades associated with Wolbachia in supergroups C and J. In other filarial clades, harbouring Wolbachia supergroups D and F, horizontal acquisitions and secondary losses are common. Finally, our results suggest that supergroup C is the basal Wolbachia clade within the Ecdysozoa. This hypothesis on the origin of Wolbachia would change drastically our understanding of Wolbachia evolution.


[Elaboration and validation of an index for preeclampsia diagnosis].
To build a consistent and valid preeclampsia diagnosis index (IDP) for its Spanish acronyms. The study was done in a Gyneco-Obstetrics Hospital and a Family Medicine Unit from March 2000 to February 2001. Fifty items were chosen from the literature, with a design to validate diagnostic tests, which were assessed by family doctors and gyneco-obstetricians in regard to their appearance and content validity. Concurrent criterion validity. Golden standard: Two gyneco-obstetricians diagnosed pre-eclampsia (hypertension and proteinuria). Simultaneously a family doctor (in an independent and blinded way) questioned, examined and recorded laboratory data of 219 preeclamptic patients and 251 non preeclamptic patients. Preeclampsia diagnosis index is an additive index with 21 clinical and paraclinical parameters weighted according to their individual diagnostic capacity. It has two parts: The first one with 82% (95%CI 80-84) sensitivity; 93% (95%CI 91-95) specificity; the second one with 86% (95%CI 83-89) sensitivity; 75% (95%CI 65-85) specificity. Preeclampsia diagnosis index is easily applied and has immediate results, which makes easier the physician's decisions.


Pulmonary mechanics during exercise in subjects with chronic airflow obstruction.
A body plethysmograph was used to measure pulmonary mechanics in six subjects with chronic airflow obstruction during steady states at rest and during exercise at 200 and 400 kpm . min-1. The mean forced expired volume in 1 s was 1.32 liters (39.2% predicted). The flow rates during tidal breathing reached the maximum expiratory flow-volume (MEFV) curve in all but one subject, and on exercise they all reached the MEFV curve. Total lung capacity did not change significantly, but functional residual capacity increased to 104% of the control value (P less than 0.05) and residual volume increased to 113.3% of the control value (P less than 0.02). The MEFV curves did not change and tidal flow rates in excess of th MEFV curve were not seen. Dynamic compliance fell with increasing exercise to 52.8% (P less than 0.01) and static expiratory pulmonary compliance to 90.2% of the control value. Transpulmonary pressures during tidal breathing when expiratory flow reached the MEFV curve increased to progressively higher values as the work load increased. At low work loads there were several subjects with negative transpulmonary pressure when maximum flow rates were present. In patients with chronic airflow obstruction, little change occurs during exercise in pulmonary mechanics; the tidal flow patterns are dominated by the expired flow-volume curve, which is not changed by exercise; maximum flow occurs in some patients when transpulmonary pressure is still negative.


The feasibility of utilizing plasma MiRNA107 and BACE1 messenger RNA gene expression for clinical diagnosis of amnestic mild cognitive impairment.
To investigate the relationship between microRNA107 (miRNA107) and BACE1 messenger RNA (mRNA) gene expressions in plasma and their diagnostic capability to distinguish subjects with amnestic mild cognitive impairment from healthy controls. We recruited 97 patients with Alzheimer's disease according to diagnostic criteria of DSM-IV and National Institute of Neurologic and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association, 116 subjects with amnestic mild cognitive impairment, and 81 healthy controls from January 2012 to December 2012. The real-time PCR was used to quantify miRNA107 and BACE1 mRNA. The power of classification accuracies between patients with amnestic mild cognitive impairment and healthy controls was performed using linear discriminate analysis single or combining both the expression miRNA107 and BACE1 mRNA. For patients with Alzheimer's disease, the miRNA107 expressions in plasma and cerebral spinal fluid were correlated (Pearson correlation = 0.665, P = .034). There were statistically significant correlations between plasma miRNA107 and BACE1 mRNA gene expression in Alzheimer's disease, amnestic mild cognitive impairment, and healthy control groups (r value = -0.316 [P = .002], -0.615 [P < .001], and -0.367 [P = .001], respectively). The overall classification accuracy of miRNA107 to discriminate between patients with amnestic mild cognitive impairment and healthy controls was 91.9%, with sensitivity of 98.3% and specificity of 82.7%. The miRNA107 expression in plasma has a high capability to discriminate between patients with amnestic mild cognitive impairment and healthy controls. ClinicalTrials.gov identifier: NCT01819545.


Analysis of cooperativity by isothermal titration calorimetry.
Cooperative binding pervades Nature. This review discusses the use of isothermal titration calorimetry (ITC) in the identification and characterisation of cooperativity in biological interactions. ITC has broad scope in the analysis of cooperativity as it determines binding stiochiometries, affinities and thermodynamic parameters, including enthalpy and entropy in a single experiment. Examples from the literature are used to demonstrate the applicability of ITC in the characterisation of cooperative systems.


Interplay among cardiac chambers. Left and right ventricular performance during changes in contractility, afterload and during simultaneous atrio-ventricular contraction.
1. Only a slight increase in stroke volume is observed during a selective left-sided inotropic stimulation of the in situ pig heart. Decreased left ventricular preload during left-sided inotropic stimulation reduces activation of the Frank-Starling mechanism and hence explains the rather small increase in stroke volume. We suggest that left-sided inotropic stimulation redistributes blood from the pulmonary circulation toward the systemic circulation causing a fall in pulmonary artery pressure and increased right ventricular output because of this afterload-reduction. 2. A rise in stroke volume during selective right-sided inotropic stimulation is not attenuated by a concomitant reduction in right ventricular preload. On the contrary, right ventricular preload rises in response to inotropic stimulation of the right atrium. Right-sided inotropic stimulation redistributes blood toward the pulmonary vascular bed and the left side of the heart. Left ventricular function is improved by this redistribution. 3. Both left ventricular end-systolic and end-diastolic volumes are better maintained by thoracic aortic occlusion during left-sided inotropic stimulation than at control inotropy. The concomitantly better preserved dimensions in the right ventricle can be explained by reduced pressure in the pulmonary circulation and a decrease in right-ward septal bulging. The rise in stroke volume by aortic occlusion during intravenous isoproterenol infusion is mainly due to a greater redistribution volume than at control inotropy. 4. Prolongation of the diastolic interval may reduce the end-diastolic pulmonary artery pressure to such an extent that right atrial contraction could eject blood into the pulmonary artery during late ventricular diastole.(ABSTRACT TRUNCATED AT 250 WORDS)


The effect of volition on the stability of bimanual coordination.
The authors investigated how the intention to passively perform a behavior and the intention to persist with a behavior impact upon the spatial and temporal properties of bimanual coordination. Participants (N = 30) were asked to perform a bimanual coordination task that demanded the continuous rhythmic extension-flexion of the wrists. The frequency of movement was scaled by an auditory metronome beat from 1.5 Hz, increasing to 3.25 Hz in.25-Hz increments. The task was further defined by the requirement that the movements be performed initially in a prescribed pattern of coordination (in-phase or antiphase) while the participants assumed one of two different intentional states: stay with the prescribed pattern should it become unstable or do not intervene should the pattern begin to change. Transitions away from the initially prescribed pattern were observed only in trials conducted in the antiphase mode of coordination. The time at which the antiphase pattern of coordination became unstable was not found to be influenced by the intentional state. In addition, the do-not-intervene set led to a switch to an in-phase pattern of coordination whereas the stay set led to phase wandering. Those findings are discussed within the framework of a dynamic account of bimanual coordination.


Magnetic resonance imaging and positron emission tomography in anti-NMDA receptor encephalitis: A systematic review.
Due to a variety of clinical manifestations anti-N-methyl-d-aspartate (NMDA) receptor encephalitis may be difficult to diagnose. Magnetic resonance imaging (MRI) may be used as a component of the workup for encephalopathy. However, the use of MRI in anti-NMDA encephalitis is complicated by wide-ranging reports regarding the frequency of normal MRI findings in this disease. Positron emission tomography (PET) is a modality of imaging that may assess functional rather than structural disturbances. Therefore, this review was conducted to summarise published studies regarding the use of MRI and PET in the diagnosis of anti-NMDA receptor encephalitis. The terms (MR OR magnetic resonance OR PET OR positron emission tomography) AND (NMDA encephalitis OR N-methyl-d-aspartate encephalitis) were used to search the databases PubMed, EMBASE and Scopus on 10/5/2017. These searches returned 1534 results. Sixty studies met the inclusion criteria. The results indicated that fewer than half of MRIs in anti-NMDA receptor encephalitis show abnormal findings. When abnormal findings are present they most commonly include T2/FLAIR medial temporal and frontal hyperintensity, and leptomeningeal contrast enhancement. Cortical grey matter changes were reported in the same number of patients as subcortical white matter changes. The only MRI finding with prognostic significance at this stage is progressive cerebellar atrophy. FDG-PET has been assessed in a few small studies and can demonstrate abnormalities in cases where MRI does not. Further research should aim for larger sample sizes and to report (and attempt to control for) the time between symptom onset and the scan being conducted, and pre-imaging treatments.


Renal transplantation in elderly patients. How to select the candidates to the waiting list?
Today, old age does not represent a formal contraindication to kidney transplantation. Rather, there is evidence that in elderly patients renal transplantation offers longer life expectancy and better quality of life in comparison with dialysis. Yet, the results of renal transplantation in recipients older than 65years are inferior to those observed in younger adults, death with functioning graft representing a major cause of failure. Therefore, the selection of aged patients is of paramount importance. Apart from the routine clinical and biological investigations, three aspects have been relatively neglected by the transplant community and may require a careful analysis in elderly candidates to transplantation: the presence and degree of frailty, the presence of comorbidities and the adherence to prescriptions. Although there are rapid and simple tests for assessing the degree of frailty in the elderly, there is no clear cut-off value to decide whether a patient should be accepted or not. With advanced age the prevalence and severity of cardiovascular events and other diseases tend to increase. The use of combined age-comorbidity indices may be helpful to identify patients at high risk of mortality. Another critical point is the poor unintentional adherence to treatment, often caused by forgetfulness and mild cognitive impairment. These drawbacks may be further enhanced by a high number of pills to take and by changes in the dosage or type of prescriptions. A careful screening of the presence and degree of frailty, comorbidity and poor compliance to treatment is highly recommended before admitting older candidates to the waiting list for transplantation.


Life course body size and lipid levels at 53 years in a British birth cohort.
To investigate the association between growth in height and change in body mass index (BMI) during the life course on lipid levels at 53 years. 2311 men and women from a British cohort study were included in analyses. Non-fasting total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels were measured at 53 years. Height and BMI at 2, 4, 7, 11, 15 and 36 years in relation to the lipid outcomes at 53 years were assessed using multiple regression models. The effects of z scores of height and BMI at 2 years and yearly rates of change (velocities) in height and BMI between 2-7, 7-15 and 15-36 years were also considered. Total cholesterol level decreased by 0.119 mmol/l (95% CI -0.194 to -0.045) per SD increase in height at 2 years and by 0.073 mmol/l (95% CI -0.145 to -0.001) for every SD increase in height velocity between 15 years and adulthood. Similar, but weaker associations were seen for LDL cholesterol. The relationships between leg length and total and LDL cholesterol were stronger than the relationship with trunk length. Higher BMI at 36 and 53 years and greater BMI increases between 15-36 and 36-53 years were associated with higher total and LDL cholesterol and lower HDL cholesterol levels. The effects of growth could not be explained by birth weight or lifetime socioeconomic status. Early life exposures, which restrict height growth in infancy, resulting in shorter adult leg length, may influence lipid levels in adult life.


Kinetic and biologic properties of recombinant ChIFN-gamma expressed via CELO-virus vector.
In this study, a replicative fowl adenovirus serotype 1 (CELO) recombinant expressing chicken interferon-gamma (ChIFN-gamma) was constructed. In the engineered recombinant, the ChIFN-gamma gene was placed under the control of cytomegalovirus (CMV) promoter. The ChIFN-gamma expression cassette was inserted in the right end of the CELO genome (D fragment), which was able to carry the largest insertion of foreign DNA without affecting the replication functions of the vector. The recombinant ChIFN-gamma (rChIFN-gamma) produced in the CELO-virus expression system was characterized by comparing its biologic activities with that of rChIFN-gamma produced via the baculovirus expression system (Bac-ChIFN-gamma). CELO-ChIFN-gamma inhibited the replication of cytolytic virus in chicken embryo fibroblasts (CEFs) and activated macrophages in a better manner than did Bac-ChIFN-gamma . Moreover, the in vitro and in vivo stability of the CELO-derived rChIFN-gamma was considerably higher than that of the Bac-ChIFN-gamma. The CELO-ChIFN-gamma recombinant vector was able to replicate in vitro in the loghorn male hepatoma (LMH) hepatocyte cell line and to produce detectable levels of recombinant cytokine in supernatant as early as 90 min post-infection. Therefore, the CELO-virus expression system is an appropriate system for high-level expression of biologically active and stable ChIFN-gamma.


Effective biliary drainage and proper treatment improve outcomes of hepatocellular carcinoma with obstructive jaundice.
We investigated the treatment outcomes and prognostic factors of hepatocellular carcinoma (HCC) with obstructive jaundice. Among 2,861 patients newly diagnosed with HCC between 2002 and 2011, a total of 63 patients who initially presented with obstructive jaundice were analyzed. Only four patients presented with resectable tumors and underwent curative resection. In the other patients who presented with unresectable tumors, 5, 8, 9, and 18 patients received transarterial chemoembolization (TACE), chemotherapy, radiotherapy, and combined treatment, respectively. Both the clinical and the treatment factors that affect overall survival (OS) were analyzed. The median OS was 4 months, and the 1-year OS rate was 23%. Patients who received treatment for HCC had a significantly improved OS rate compared with the patients who received supportive care only (1-year OS, 32% vs 0%; p<0.01). Responders to treatment showed a better OS than nonresponders (1-year OS, 52% vs 0%; p<0.01). TACE and radiotherapy resulted in relatively good treatment responses of 64% and 67%, respectively. In multivariate analyses, treatment of HCC (p=0.02) and the normalization of serum bilirubin by biliary drainage (p=0.02) were significantly favorable prognostic factors that affected the OS. Unresectable HCC with obstructive jaundice has a poor prognosis. However, effective biliary drainage and treatment of HCC such as with TACE or radiotherapy improves survival.


Integrating spirituality into patient care: an essential element of person‑centered care.
Spirituality and health is a growing field of healthcare. It grew out of courses in spirituality and health developed for medical students in the United States. Research in this area over the last 30 years has also formed an evidence base for spirituality and health. Studies have demonstrated an association between spiritual beliefs and values and a variety of healthcare outcomes. More recent research has also shown a strong desire on the part of patients to have their spirituality addressed as part of their care. Studies also show that spiritual care has an impact on patient decision making, particularly in end-of-life care. The Association of American Medical Colleges developed a broad definition of spirituality as well as learning objectives and guidelines for teaching. Standards in organizations such as the American College of Physicians support physicians treating the whole person, that is, the body, mind, and spirit. In 2009, National Competencies in Spirituality and Health education were developed in the United States with schools currently working on curriculum projects based on these competencies. Models are being developed for all members of the healthcare team to address patient distress, in cooperation with chaplains as spiritual care experts. The goals are to develop a biopsychosocial and spiritual assessment and treatment as part of compassionate whole-person care of all patients.


Multivariate sexual selection in a rapidly evolving speciation phenotype.
Estimating the fitness surface of rapidly evolving secondary sexual traits can elucidate the origins of sexual isolation and thus speciation. Evidence suggests that sexual selection is highly complex in nature, often acting on multivariate sexual characters that sometimes include non-heritable components of variation, thus presenting a challenge for predicting patterns of sexual trait evolution. Laupala crickets have undergone an explosive species radiation marked by divergence in male courtship song and associated female preferences, yet patterns of sexual selection that might explain this diversification remain unknown. We used female phonotaxis trials to estimate the fitness surface for acoustic characters within one population of Laupala cerasina, a species with marked geographical variation in male song and female preferences. Results suggested significant directional sexual selection on three major song traits, while canonical rotation of the matrix of nonlinear selection coefficients (γ) revealed the presence of significant convex (stabilizing) sexual selection along combinations of characters. Analysis of song variation within and among males indicated significantly higher repeatability along the canonical axis of greatest stabilizing selection than along the axis of greatest linear selection. These results are largely consistent with patterns of song divergence that characterize speciation and suggest that different song characters have the potential to indicate distinct information to females during courtship.


An analysis of functional shoulder movements during task performance using Dartfish movement analysis software.
Video-based movement analysis software (Dartfish) has potential for clinical applications for understanding shoulder motion if functional measures can be reliably obtained. The primary purpose of this study was to describe the functional range of motion (ROM) of the shoulder used to perform a subset of functional tasks. A second purpose was to assess the reliability of functional ROM measurements obtained by different raters using Dartfish software. Ten healthy participants, mean age 29 ± 5 years, were videotaped while performing five tasks selected from the Disabilities of the Arm, Shoulder and Hand (DASH). Video cameras and markers were used to obtain video images suitable for analysis in Dartfish software. Three repetitions of each task were performed. Shoulder movements from all three repetitions were analyzed using Dartfish software. The tracking tool of the Dartfish software was used to obtain shoulder joint angles and arcs of motion. Test-retest and inter-rater reliability of the measurements were evaluated using intraclass correlation coefficients (ICC). Maximum (coronal plane) abduction (118° ± 16°) and (sagittal plane) flexion (111° ± 15°) was observed during 'washing one's hair;' maximum extension (-68° ± 9°) was identified during 'washing one's own back.' Minimum shoulder ROM was observed during 'opening a tight jar' (33° ± 13° abduction and 13° ± 19° flexion). Test-retest reliability (ICC = 0.45 to 0.94) suggests high inter-individual task variability, and inter-rater reliability (ICC = 0.68 to 1.00) showed moderate to excellent agreement. KEY FINDINGS INCLUDE: 1) functional shoulder ROM identified in this study compared to similar studies; 2) healthy individuals require less than full ROM when performing five common ADL tasks 3) high participant variability was observed during performance of the five ADL tasks; and 4) Dartfish software provides a clinically relevant tool to analyze shoulder function.


Executive processes in appearance-reality tasks: the role of inhibition of attention and symbolic representation.
Two studies addressed the role of representation ability and control of attention on solutions to an appearance-reality task based on two types of objects, real and representational. In Study 1, 67 preschool children (3-, 4-, and 5-year-olds) solved appearance-reality problems and executive processing tasks. There was an interaction between object type (real vs. representational) and question type (appearance vs. reality) on problem difficulty. In addition, representational ability predicted performance on appearance questions and inhibitory control predicted performance on reality questions. In Study 2, 95 children (4- and 5-year-olds) who were monolingual or bilingual solved similar problems. On appearance questions, groups performed equivalently but on reality questions, bilinguals performed better (once language proficiency had been controlled). The difference is attributed to the advanced inhibitory control that comes with bilingualism.


Intergenerational Effects of Discrimination on Black American Children's Sleep Health.
Greater exposure to racial/ethnic discrimination among pregnant Black American women is associated with elevated prenatal depressive symptomatology, poorer prenatal sleep quality, and poorer child health outcomes. Given the transdiagnostic importance of early childhood sleep health, we examined associations between pregnant women's lifetime exposure to racial/ethnic discrimination and their two-year-old children's sleep health. We also examined women's gendered racial stress as a predictor variable. In exploratory analyses, we examined prenatal sleep quality and prenatal depressive symptoms as potential mediators of the prior associations. We utilized data from a sample of Black American women and children (n = 205). Women self-reported their lifetime experiences of discrimination during early pregnancy, their sleep quality and depressive symptoms during mid-pregnancy, and their children's sleep health at age two. Hierarchical linear multiple regression models were fit to examine direct associations between women's experiences of discrimination and children's sleep health. We tested our mediation hypotheses using a parallel mediator model. Higher levels of gendered racial stress, but not racial/ethnic discrimination, were directly associated with poorer sleep health in children. Higher levels of racial/ethnic discrimination were indirectly associated with poorer sleep health in children, via women's prenatal depressive symptomatology, but not prenatal sleep quality. Clinical efforts to mitigate the effects of discrimination on Black American women may benefit women's prenatal mental health and their children's sleep health.


Multiple-antigen slide test for detection of immunoglobulin M antibodies in newborn and infant sera by immunofluorescence.
A microimmunofluorescence test was evaluated for use in measuring immunoglobulin M (IgM) antibodies in infant sera to five of the agents implicated in congenital and neonatal disease. Pen point dots of Toxoplasma gondii, cytomegalovirus, rubella virus, herpes simplex virus, and chlamydial cell culture antigens were applied to each circle of eight-circle printed slides. These multiple-antigen slides greatly facilitated the screening of 607 sera from infants and 117 sera from mothers for the presence of IgM antibody to these agents. Forty sera could be examined microscopically in approximately 30 min. All sera reacting with one or more antigens were tested for rheumatoid factor by the latex method, absorbed with glutaraldehyde-cross-linked human IgG, and retested for the presence of IgM antibody. IgM antibody to cytomegalovirus was demonstrated in sera from four newborns, but IgM antibody to rubella virus could not be detected until 21 days after birth, although rubella virus was isolated from sera from five younger infants. This may indicate that rubella IgM levels in many congenitally infected newborns are too low to be measured by the immunofluorescence method. Five percent of the sera from infants in this study possessed demonstrable IgM antibody to one of the antigens.


Tumor Immunity and Immunotherapy for HPV-Related Cancers.
Human papillomavirus (HPV) infection drives tumorigenesis in the majority of cervical, oropharyngeal, anal, and vulvar cancers. Genetic and epidemiologic evidence has highlighted the role of immunosuppression in the oncogenesis of HPV-related malignancies. Here we review how HPV modulates the immune microenvironment and subsequent therapeutic implications. We describe the landscape of immunotherapies for these cancers with a focus on findings from early-phase studies exploring antigen-specific treatments, and discuss future directions. Although responses across these studies have been modest to date, a deeper understanding of HPV-related tumor biology and immunology may prove instrumental for the development of more efficacious immunotherapeutic approaches. SIGNIFICANCE: HPV modulates the microenvironment to create a protumorigenic state of immune suppression and evasion. Our understanding of these mechanisms has led to the development of immunomodulatory treatments that have shown early clinical promise in patients with HPV-related malignancies. This review summarizes our current understanding of the interactions of HPV and its microenvironment and provides insight into the progress and challenges of developing immunotherapies for HPV-related malignancies.


[Hemorrhagic herpes encephalitis. A difficult differential diagnosis with computerized tomography].
Herpes simplex encephalitis (HSE) is the most common sporadically appearing encephalitis in Central Europe. Differential diagnosis to brain tumors or spontaneous intercerebral hemorrhage is difficult. There are CT scan findings which are characteristic of HSE but there are no pathognomonic patterns. These characteristic findings are helpful in differential diagnosis to neoplastic or vascular processes. Thus, other diagnostic procedures (i.e. brain biopsy) to confirm diagnosis of HSE and effective therapy may be carried out in time. The difficulties in differential diagnosis are shown by the presented case.


Changes in arginine metabolism during sepsis and critical illness in children.
Arginine is an important amino acid during disease and healing because of functions in the immune system and as precursor of nitric oxide (NO). In critically ill adults and children, plasma arginine and citrulline concentrations are substantially decreased, indicating an arginine-deficient state. Arginine availability is reduced because of increased arginine disposal in combination with reduced de novo arginine synthesis. The latter is most likely caused by reduced citrulline availability. As a result, NO synthesis may be impaired, which might compromise microcirculation. These metabolic changes seem to be dependent on the severity of inflammation. Arginine or citrulline supplementation in severe inflammation might therefore be beneficial. Possibly, the use of protein-energy-enriched formulas may be a first step to improve arginine availability and NO synthesis. In critically ill children, arginine metabolism and supplementation is however a virtually unexplored field. Since pediatric sepsis is a significant health problem, which differs in epidemiology and pathophysiology from sepsis in adults, and because of the scarcity of data in this population, studies focused on pathophysiological mechanisms and possible interventions in arginine metabolism in pediatric critical illness are warranted.


Peakr: simulating solid-state NMR spectra of proteins.
When analyzing solid-state nuclear magnetic resonance (NMR) spectra of proteins, assignment of resonances to nuclei and derivation of restraints for 3D structure calculations are challenging and time-consuming processes. Simulated spectra that have been calculated based on, for example, chemical shift predictions and structural models can be of considerable help. Existing solutions are typically limited in the type of experiment they can consider and difficult to adapt to different settings. Here, we present Peakr, a software to simulate solid-state NMR spectra of proteins. It can generate simulated spectra based on numerous common types of internuclear correlations relevant for assignment and structure elucidation, can compare simulated and experimental spectra and produces lists and visualizations useful for analyzing measured spectra. Compared with other solutions, it is fast, versatile and user friendly. Peakr is maintained under the GPL license and can be accessed at http://www.peakr.org. The source code can be obtained on request from the authors.


The effect of including Lactobacillus reuteri KUB-AC5 during post-hatch feeding on the growth and ileum microbiota of broiler chickens.
The probiotic strain Lactobacillus reuteri KUB-AC5, which was originally isolated from chicken intestine, was fed to newborn broiler chicks for the first week post-hatch. The growth and ileum microbiota of the chickens were carefully monitored for 6 wk. The inclusion of 5 log cfu/g of feed statistically increased the BW gain in the first week compared with that of the control group, but this effect did not continue thereafter. Significant effects on host feed consumption and the feed-to-growth conversion ratio were not detected. The total amount and composition of ileum bacteria were investigated by quantitative PCR and pyrosequencing of the 16S rRNA gene (rDNA), respectively, and were compared between the control and the probiotic-treated groups. The amount of total bacterial 16S rDNA in ileum samples at d 42 was 5 times higher in the probiotic group than in the control, whereas no significant difference was observed at d 21. A composition analysis revealed the establishment of lactobacilli-enriched microbiota in the probiotic-treated chickens at d 42. At this point, the population level and species diversity of lactobacilli were significantly enhanced compared with those of the control group. In addition, Actinobacteria, mainly genera Corynebacterium and Dietzia, were also statistically higher in the probiotic group. However, Proteobacteria, including those of the family Campylobacterales and some other nonbeneficial bacterial groups, were decreased in the probiotic group at the growing stage. Therefore, with probiotic supplementation, it was demonstrated that Lactobacillus reuteri KUB-AC5 in the early post-hatching period had a delayed effect on ileum microbiota, which resulted in the enrichment of potentially beneficial lactobacilli and the suppression of Proteobacteria, including nonbeneficial bacterial groups.


Thermal-stress analysis of ceramic laminate veneer restorations with different incisal preparations using micro-computed tomography-based 3D finite element models.
Main objective of this study is to investigate the thermal behavior of ceramic laminate veneer restorations of the maxillary central incisor with different incisal preparations such as butt joint and palatinal chamfer using finite element method. In addition, it is also aimed to understand the effect of different thermal loads which simulates hot and cold liquid imbibing in the mouth. Three-dimensional solid models of the sound tooth and prepared veneer restorations were obtained using micro-computed tomography images. Each ceramic veneer restoration was made up of ceramic, luting resin cement and adhesive layer which were generated based on the scanned images using computer-aided design software. Our solid model also included the remaining dental tissues such as periodontal ligament and surrounding cortical and spongy bones. Time-dependent linear thermal analyses were carried out to compare temperature changes and stress distributions of the sound and restored tooth models. The liquid is firstly in contact with the crown area where the maximum stresses were obtained. For the restorations, stresses on palatinal surfaces were found larger than buccal surfaces. Through interior tissues, the effect of thermal load diminished and smaller stress distributions were obtained near pulp and root-dentin regions. We found that the palatinal chamfer restoration presents comparatively larger stresses than the butt joint preparation. In addition, cold thermal loading showed larger temperature changes and stress distributions than those of hot thermal loading independent from the restoration technique.


Effects of ADP on sarcoplasmic reticulum function in mechanically skinned skeletal muscle fibres of the rat.
1. The sarcoplasmic reticulum (SR) Ca(2+) content (expressed in terms of endogenous SR Ca(2+) content under physiologically resting conditions and measured from caffeine-induced force responses) and the effective rates of the SR Ca(2+) pump and SR Ca(2+) leak (measured from the temporal changes in SR Ca(2+) content) were determined in mechanically skinned skeletal muscle fibres of the rat at different [ADP] (< 0.10 microM to 1.04 mM). 2. The estimated SR Ca(2+) pump rate at 200 nM Ca(2+) did not change when [ADP] increased from below 0.10 microM to 10 microM but decreased by about 30 % when [ADP] increased from 10 microM to 1.04 mM. 3. The rate constant of SR Ca(2+) leak increased markedly with rising [ADP] when [Ca(2+)] in solution was 200 nM (apparent dissociation constant Kd(ADP) = 64 +/- 27 microM). Decreasing the [Ca(2+)] in solution from 200 nM to < 10 nM significantly increased the leak rate constant at all [ADP]. The SR Ca(2+) leak rate constant could be significantly reduced by blocking the SR Ca(2+) pump with 2,5-di(tert-butyl)-1,4-hydroquinone (TBQ). 4. The decrease in the SR Ca(2+) pump rate and the increase in the rate constant of SR Ca(2+) leak when the [ADP] increased from < 0.10 microM to 1.04 mM caused a 4.4-fold decrease in SR Ca(2+) loading ability at 200 nM Ca(2+). 5. The results can be fully explained by a mechanism whereby the presence of ADP causes a marked increase in the ADP-sensitive fraction of the phosphorylated pump protein, which can act as a Ca(2+)-Ca(2+) exchanger and demonstrates that ADP is an important modulator of SR function in skeletal muscle.


CELL BIOLOGY SYMPOSIUM: Practical application of the basic aspects of GLUT4 membrane trafficking and insulin signaling on issues related to animal agriculture.
Because of the relatively short lifespans of beef cattle, membrane trafficking in relation to inflammation is not considered important unless it overtly affects productivity. However, glucose uptake and utilization is important for adipose tissue development in beef cattle, and increasing glucose utilization in intramuscular adipose tissue can increase carcass quality. Research from the 1980s demonstrated a lack of insulin sensitivity in isolated bovine adipocytes and adipose tissue explants incubated in vitro. Insulin did not stimulate glucose or acetate incorporation into fatty acids, nor did it increase concentrations of glycolytic intermediates in bovine adipose tissue incubated with exogenous glucose. Specific binding of [I] iodoinsulin and insulin degradation in bovine isolated adipocytes was low to non-detectable. These early studies indicated that insulin-dependent receptor-mediated signaling was less important in bovine adipose tissue than in adipose tissues of humans, swine, or laboratory species. More recent research demonstrated that glucose transporter protein 4 (GLUT4) expression in muscle and adipose tissue declines markedly after birth in calves, indicating the development of insulin resistance as cattle transition from suckling to functional ruminants. Insulin resistance is important in dairy cattle, causing ketosis and fatty liver. Consistent with this, subcutaneous adipose tissue expression decreases 50% following parturition in dairy cattle, although expression of genes associated with insulin responsiveness (, , and ) is up-regulated by 21 d postpartum. Understanding the underlying mechanisms of insulin resistance in beef and dairy cattle would increase animal health and thereby improve productivity.


Does a general surgery clerkship influence student perceptions of surgeons and surgical careers?
Student perceptions of surgeons and surgical careers may influence their decision to pursue a surgical career. We evaluated the impact of a general surgery clerkship on medical student perceptions of surgeons and surgical careers and of the clerkship on student interest in surgical careers. We conducted voluntary pre- and postclerkship surveys of third-year medical students who were enrolled in their required general surgery clerkship and used 5-point Likert scale rankings to capture agreement with declarative statements (1 = strongly agree; 5 = strongly disagree). T-tests were used to evaluate both paired and individual items. Students indicated that their surgical clerkship improved their opinion of surgeons (2.47; P <.001). Several perceptions changed after the clerkship. First, students agreed more strongly that surgeons were compassionate physicians (ranking, 2.87 vs 2.53; P =.003) and that patients respected surgeons (ranking, 1.84 vs 1.62; P =.026). Acknowledgment of career satisfaction by students increased (ranking, 2.57 vs 2.22; P =.008). Students more strongly disagreed that "surgeons [were] respectful of other physicians" (ranking, 3.29 vs 3.62; P =.009). Interest in surgical careers did not change significantly during the clerkship (ranking, 2.83 vs 2.68; P =.218). Medical student perceptions of surgeons and surgical careers generally improve during the surgical clerkship. However, student impressions of surgeons' collegial behavior and commitment to teaching deteriorate significantly during the surgical clerkship.


Immunohistochemical analysis of estrogen receptors in the urethra of sexually intact, ovariectomized, and estrogen-substituted ovariectomized sheep.
Urinary incontinence is prevalent in postmenopausal women and spayed dogs and is associated with decreased estrogen plasma concentrations. The objective of the study was to investigate the expression of estrogen receptors (ER) in the urethra of sexually intact, ovariectomized, and estrogen-substituted ovariectomized ewes. Paraffin cross-sections from each urethral quarter were immunohistochemically analyzed. The reactivity of ER was semiquantitatively assessed employing an immunoreactive score (IRS). In contrast to ERβ, ERα was identified in all urethral compartments; the highest IRS was detected in the epithelium of the distal urethra. The immunoreactivity and distribution of ERα did not differ among groups. Highly significant differences in ERα concentrations were observed between consecutive urethral quarters in each group. Neither ovariectomy nor ovariectomy and estrogen substitution seem to have a significant effect on overall urethral ERα concentration. The results demonstrate that the precise location of the investigated urethral part is crucial to the reliable evaluation or possible comparison of ERα concentrations.


Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study.
BRCA1 and BRCA2 screening in women at high-risk of breast cancer results in the identification of both unambiguously defined deleterious mutations and sequence variants of unknown clinical significance (VUS). We examined a population-based sample of young women with contralateral breast cancer (CBC, n=705) or unilateral breast cancer (UBC, n=1398). We identified 470 unique sequence variants, of which 113 were deleterious mutations. The remaining 357 VUS comprised 185 unique missense changes, 60% were observed only once, while 3% occurred with a frequency of >10%. Deleterious mutations occurred three times more often in women with CBC (15.3%) than in women with UBC (5.2%), whereas combined, VUS were observed in similar frequencies in women with CBC and UBC. A protein alignment algorithm defined 16 rare VUS, occurring at highly conserved residues and/or conferring a considerable biochemical difference, the majority located in the BRCA2 DNA-binding domain. We confirm a multiplicity of BRCA1 and BRCA2 VUS that occur at a wide range of allele frequencies. Although some VUS inflict chemical differences at conserved residues, suggesting a deleterious effect, the majority are not associated with an increased risk of CBC.


Correlation between compliance in patients with anti-hypertensive therapy and blood pressure control.
This paper aims to understand the blood pressure control status for hypertension patients, and discuss the relationship between social support, medication compliance and blood pressure for hypertensive patients. The survey objective was the hypertensive patients in chronic disease management system in Xinxiang city. The survey was conducted as the questionnaire survey filled by objectives. Social support rating scale and medication therapy compliance questionnaire was utilized to evaluate the patients' social support and medication therapy compliance. 1095 patients in medication were investigated, the blood pressure of 66.6% investigated objectives was controlled at target levels (<140/90 mmHg), 70.0% investigated objectives have good medication therapy compliance; the overall social support score for hypertensive patients in medication was (40.01±6.54) points, the subjective support score, objective support score and support utilization degree score were respectively (24.43±4.61) points, (8.59±2.59) points and (7.00±2.06) points; Rank correlation coefficient of Spearman illustrated that the support utilization rating evaluation was apparently correlated to medication therapy compliance (rs=0.88, P<0.01); multivariate analysis proved that the protective factors for medication therapy compliance were the high support utilization rate (OR 1.62; 95%CI 1.19~2.05), long hypertensive duration (5~10 years: OR 2.01, 95%CI 1.42~2.73; more than 10 years: OR 1.46, 95%CI 1.01~1.99) and high average monthly household income (OR 2.03, 95%CI 1.45~2.69); Risk factor for blood pressure control were male (OR 0.61, 95% CI 0.47~0.79) and high hypertensive grade (OR 0.31, 95%CI 0.19~0.44); The protective factors for blood pressure control was good medication therapy compliance (OR 1.54, 95%CI 1.22~1.89), (average P<0.05). It required to build effective social support system, increase patients' social support utilization degree, emphasized the intervention on low average monthly household incomes, male higher rate, higher hypertensive degree, and further improve the medication therapy compliance and hypertensive control rate of hypertensive patients.


The Critical Role of Nutrition Care to Improve Pain Management: A Global Call to Action for Physical Therapist Practice.
Physical therapists have unique education in the comprehensive biopsychosocial assessment and treatment of chronic pain and its mechanisms. Recently, physical therapists have raised awareness regarding the impact of nutrition on promoting health and managing noncommunicable diseases. Robust evidence supports the implementation of nutrition in physical therapist education and practice. Of particular interest for the physical therapist are investigations that use dietary interventions for the treatment of chronic pain. Yet physical therapists have received little guidance regarding their role in nutrition care for pain management and may pass on opportunities to counsel their patients on the connection between nutrition and pain. Therefore, a clinical paradigm shift and unified voice within the profession is called on to encourage physical therapists to develop tailored multimodal lifestyle interventions that include nutrition care for the management of chronic pain. This Perspective describes evidence supporting the implementation of nutrition care in physical therapist practice, supports the role of nutritional pain management for physical therapists, and encourages the use of nutrition care for primary, secondary, tertiary, prevention, health promotion, and wellness related to chronic pain. To achieve these aims, this Perspective offers suggestions for how physical therapists can (1) enhance clinical decision making; (2) expand professional, jurisdictional, and personal scope of practice; (3) evolve entry-level education; and (4) stimulate new investigations in nutrition care and pain science research. In doing so, physical therapists can assert their role throughout the pain management continuum, champion innovative research initiatives, and enhance public health by reducing the impact of chronic pain. The nutrition care process for pain management is defined as the basic duty to provide adequate and appropriate nutrition education and counseling to people living with pain. Including the nutrition care process as part of a multimodal approach to pain management provides an opportunity for physical therapists to assert their role throughout the pain management continuum. This includes championing innovative research initiatives and enhancing public health by reducing the impact of chronic pain for over 50 million Americans.


Thymus-dependent areas in the lymphoid organs of neonatally thymectomized mice.
Specific areas of lymphocyte depletion, termed thymus-dependent areas, have been delineated in neonatally thymectomized C3H/Bi and F(1) (C57BL x C3H/Bi) mice. They occur within the lymphoid follicles of the spleen immediately surrounding the central arterioles, and constitute the mid and deep cortical zones of the lymph nodes. These depleted areas appear in healthy thymectomized mice as early as 3 wk after operation but, in mice which survive for more than 6 to 7 wk, the thymus-dependent areas are repopulated by rapidly dividing pyroninophilic cells, the majority of which are immature plasma cells. Syngeneic thymus cells, labeled in vitro with tritiated adenosine localize preferentially in the thymus-dependent areas after intravenous injection. Similarly labeled spleen cells also accumulate in these areas but, in addition, are distributed at the periphery of splenic follicles and in the outer cortical zone of the lymph nodes. Many more spleen than thymus cells enter the lymphoid tissues and the spleen appears to be the primary target. The apparent paradox that syngeneic thymus cells are less efficient than spleen cells in restoring neonatally thymectomized mice to normality is discussed in the light of these results and possible routes by which the migrating cells could enter the lymphoid tissues are considered. The origin of the plasma cells which repopulate the lymphocyte depleted areas is also discussed. It is concluded that the normal thymus produces cells which contribute directly to the migratory or circulatory lymphocyte population but that there also exists another source of supply for the plasma cell series. These two systems may function synergistically so that the thymus may control, directly or indirectly, the balance of cell populations within the body.


Unexpected destruction of chitosomal chitin synthetase by an endogenous protease during sucrose density gradient purification.
Because of their intrinsic low buoyant density, chitosomes can be separated from crude cell homogenates (1000 g or 35,000 g supernatants) of Mucor rouxii by isopycnic sedimentation in sucrose density gradients. To accelerate and simplify the isolation of chitosomes, we centrifuged the cell-free extracts at ultrahigh speed (in a fixed-angle rotor at forces up to 311,000 g Rav) and found that the duration of centrifugation was critical. Prolonged centrifugation at ultrahigh speed caused severe distortion of the chitin synthetase profile in the gradient as the peak of chitosomal chitin synthetase nearly disappeared. We traced the problem to a soluble protease(s) that moved into the chitosome band during protracted centrifugation and destroyed the chitin synthetase activity. The interfering protease was a soluble protein with a sedimentation coefficient of 4.6 S and a pH optimum of 7-7.5, and it was sensitive to PMSF (phenylmethylsulfonyl fluoride), indicating that it was a serine protease. Unlike other proteases, it destroyed chitin synthetase but did not activate the chitin synthetase zymogen. The interfering protease could be eliminated either by adding PMSF to the cells immediately after breakage or by removing the upper part of the sucrose gradient midway through the centrifugation of the cell-free extract and then completing the sedimentation with the 'decapitated' gradient.


The circulation in sleep in newborn lambs.
Interaction of the cardiovascular, homeothermic and behavioural systems has particular significance in early life as this period of development sees high cardiac output, limited circulatory reserves, a particular vulnerability to thermal stress, and long periods of rapid eye movement (REM) sleep during which thermal regulation may be suspended. In unstressed lambs, significant cardiovascular differences exist between behavioural states of sleep and wakefulness, with the REM sleep-state being outstanding. In REM sleep there is wide cardiac output variation, a low heart rate, and a high stroke volume. High levels of cardiac output occurring in combination with poorer oxygenation and respiration in REM may represent a risk to the newborn, as cardiac performance is already high and reserves are low in comparison with the adult. Lambs respond to cool stress with increases of cardiac output and oxygen consumption in wakefulness and quiet sleep, but not in REM sleep. Suspension of thermoregulatory processes in REM sleep also points to this as the more vulnerable state for the newborn. Arousal responses from quiet sleep or REM sleep to wakefulness occur if lambs are subjected to acute reductions of blood pressure. There is a delay before arousal which is longer in REM sleep than in quiet sleep. Animals fail to arouse in approximately 40% of hypotensive tests in both states. This shared feature of the sleep-states (failure to arouse) may be more important than the state-related difference (longer delay before arousal in REM) in understanding a cardiovascular mechanism of Sudden Infant Death Syndrome.


The imaging of myositis ossificans.
Myositis ossificans (MO) is characterized by abnormal heterotopic bone formation involving striated muscle, tendons, ligaments, fasciae, and aponeuroses. Myocardium, the diaphragm, tongue, larynx, smooth muscle, and sphincters are all spared. Several subtypes of myositis ossificans exist: posttraumatic myositis ossificans (PTMO), nontraumatic/pseudomalignant myositis ossificans, and myositis ossificans progressiva (MOP). This article reviews the clinical features and differential diagnoses of each subtype of MO and illustrates the typical imaging features demonstrated by plain radiography, ultrasound, radionuclide bone scans, computed tomography, and magnetic resonance imaging.


Tissue transglutaminase selectively modifies gliadin peptides that are recognized by gut-derived T cells in celiac disease.
The action of tissue Transglutaminase (TGase) on specific protein-bound glutamine residues plays a critical role in numerous biological processes. Here we provide evidence for a new role of this enzyme in the common, HLA-DQ2 (and DQ8) associated enteropathy, celiac disease (CD). The intestinal inflammation in CD is precipitated by exposure to wheat gliadin in the diet and is associated with increased mucosal activity of TGase. This enzyme has also been identified as the main target for CD-associated anti-endomysium autoantibodies, and is known to accept gliadin as one of its few substrates. We have examined the possibility that TGase could be involved in modulating the reactivity of gliadin specific T cells. This could establish a link between previous reports of the role of TGase in CD and the prevailing view of CD as a T-cell mediated disorder. We found a specific effect of TGase on T-cell recognition of gliadin. This effect was limited to gliadin-specific T cells isolated from intestinal CD lesions. We demonstrate that TGase mediates its effect through an ordered and specific deamidation of gliadins. This deamidation creates an epitope that binds efficiently to DQ2 and is recognized by gut-derived T cells. Generation of epitopes by enzymatic modification is a new mechanism that may be relevant for breaking of tolerance and initiation of autoimmune disease.


Combined PCL-ACL lateral and medial side injuries: treatment and results.
The multiple ligament-injured knee is a complex problem in orthopedic surgery. These injuries may or may not present as acute knee dislocations, and careful assessment of the extremity vascular and neurologic status is essential because of the possibility of arterial and/or venous compromise, and nerve injury. These complex injuries require a systematic approach to evaluation and treatment. Physical examination and imaging studies enable the surgeon to make a correct diagnosis and formulate a treatment plan. Knee stability is improved postoperatively when evaluated with knee ligament rating scales, arthrometer testing, and stress radiographic analysis. Surgical timing depends on the injured ligaments, vascular status of the extremity, reduction stability, and the overall health of the patient. The use of allograft tissue is preferred because of the strength of these large grafts, and the absence of donor site morbidity.


Stretching self-entangled DNA molecules in elongational fields.
We present experiments of self-entangled DNA molecules stretching under a planar elongational field, and their stretching dynamics are compared to identical molecules without entanglements. Self-entangled molecules stretch in a stage-wise fashion, persisting in an "arrested" state for decades of strain prior to rapidly stretching, slowing down the stretching dynamics by an order of magnitude compared to unentangled molecules. Self-entangled molecules are shown to proceed through a transient state where one or two ends of the molecule are protruding from an entangled, knotted core. This phenomenon sharply contrasts with the wide array of transient configurations shown here and by others for stretching polymers without entanglements. The rate at which self-entangled molecules stretch through this transient state is demonstrably slower than unentangled molecules, providing the first direct experimental evidence of a topological friction. These experimental observations are shown to be qualitatively and semi-quantitatively reproduced by a dumbbell model with two fitting parameters, the values of which are reasonable in light of previous experiments of knotted DNA.


Examining spatial patterns of selection and use for an altered predator guild.
Anthropogenic disturbances have altered species' distributions potentially impacting interspecific interactions. Interference competition is when one species denies a competing species access to a resource. One mechanism of interference competition is aggression, which can result in altered space-use of a subordinate species due to the threat of harm, otherwise known as a 'landscape of fear'. Alternatively, subordinates might outcompete dominant species in resource-poor environments via a superior ability to extract resources. Our goal was to evaluate spatial predictions of the 'landscape of fear' hypothesis for a carnivore guild in Newfoundland, Canada, where coyotes recently immigrated. Native Newfoundland carnivores include red foxes, Canada lynx, and black bears. We predicted foxes and lynx would avoid coyotes because of their larger size and similar dietary niches. We used scat-detecting dogs and genetic techniques to locate and identify predator scats. We then built resource selection functions and tested for avoidance by incorporating predicted values of selection for the alternative species into the best supported models of each species. We found multiple negative relationships, but notably did not find avoidance by foxes of areas selected by coyotes. While we did find that lynx avoided coyotes, we also found a reciprocal relationship. The observed patterns suggest spatial partitioning and not coyote avoidance, although avoidance could still be occurring at different spatial or temporal scales. Furthermore, Newfoundland's harsh climate and poor soils may swing the pendulum of interspecific interactions from interference competition to exploitative competition, where subordinates outcompete dominant competitors through a superior ability to extract resources.


Procoagulant activity of platelets.
A simplified, semiautomated, quantitative method to evaluate platelet procoagulant activity was evaluated on plasma that contained widely divergent concentrations of platelets. When fewer than 100,000 platelets/cu mm were present, excellent correlation between platelet concentration and clotting time was noted, with correlation best in the range 30,000 to 100,000 platelets/cu mm. When platelets were present in concentrations greater than 100,000/cu mm, no alteration in clotting time as a function of platelet count was noted. These observations were consistent with clinical observations that patients with greater than 100,000 platelets rarely bleed and that those with fewer than 30,000 platelets bleed in an unpredictable fashion. The procedure appears to be of potential value in evaluation of patients for defects in platelet factor 3 release.


A clinically relevant review of hip biomechanics.
The hip is a complex anatomic structure composed of osseous, ligamentous, and muscular structures responsible for transferring the weight of the body from the axial skeleton into the lower extremities. This must be accomplished while allowing for dynamic loading during activities such as gait and balance. The evaluation of hip pain and periarticular pathology can be challenging because of the complex local anatomy and broad differential diagnosis. Recent advancements in the evaluation and surgical treatment of hip pathology have led to a renewed interest in the management of these disorders. An understanding of the basic biomechanical and kinematic function of the hip and the consequences of associated pathology can greatly assist the orthopaedic surgeon in appropriately diagnosing and treating these problems. In this review we discuss the basic biomechanical concepts of the native hip and surrounding structures and the changes experienced as a result of various pathologies including dysplasia, femoroacetabular impingement, labral injury, capsular laxity, hip instability, and articular cartilage injury. We will also discuss the clinical implications and surgical management of these pathologies and their role in restoring or preserving the native function of the hip joint.


Probing Intermolecular Interactions in Phospholipid Bilayers by Far-Infrared Spectroscopy.
Fast thermal fluctuations and low frequency phonon modes are thought to play a part in the dynamic mechanisms of many important biological functions in cell membranes. Here we report a detailed far-infrared study of the molecular subpicosecond motions of phospholipid bilayers at various hydrations. We show that these systems sustain several low frequency collective modes and deduce that they arise from vibrations of different lipids interacting through intermolecular van der Waals forces. Furthermore, we observe that the low frequency vibrations of lipid membrane have strong similarities with the subpicosecond motions of liquid water and suggest that resonance mechanisms are an important element to the dynamics coupling between membranes and their hydration water.


The effect of high-, moderate-, and low-fat diets on weight loss and cardiovascular disease risk factors.
Over 60% of Americans are overweight and a number of popular diets have been advocated, often without evidence, to alleviate this public health hazard. This study was designed to investigate the effects of several diets on weight loss, serum lipids, and other cardiovascular disease risk factors. One hundred men and women followed one of four dietary programs for 1 year: a moderate-fat (MF) program without calorie restriction (28 patients); a low-fat (LF) diet (phase I) (16) ; a MF, calorie-controlled (phase II) diet (38 patients); and a high-fat (HF) diet (18 subjects) [corrected]. Weight, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), homocysteine (Ho), and lipoprotein(a) [Lp(a)], were measured every 4th month. The TC/HDL-C ratio was calculated and fibrinogen levels were measured at baseline and after one year. The MF diet resulted in a 2.6% (NS) decrease in weight compared with 18.4% (p=0.045) decrease in patients on phase I, 12.6% (p=0.0085) decrease in patients on phase II, and 13.7% (p=0.025) decrease in those on the HF diet. TC was reduced by 5% (NS) in the MF group, 39.1% (p=0.0005) in the phase I group, and 30.4% (p=0.0001) in the phase II group. HF group had a 4.3% (NS) increase in TC. LDL-C was reduced by 6.1% (NS) on MF, 52.0% (p=0.0001) on phase I, and 38.8% (p=0.0001) on phase II. Patients on HF had a 6.0% (NS) increase in LDL-C. There were nonsignificant reductions in HDL-C in those on MF (-1.5%) and HF (-5.8%). Patients on phase I showed an increase in HDL-C of 9.0% (NS), while those on phase II diet had a 3.6% increase (NS) in HDL-C. TC/HDL-C increased (9.8%) only in patients following the high-fat diets (NS). Patients on MF had a 5.3% (NS) reduction in TC/HDL-C, while those on LF had significant reductions on the phase I ( -45.8%; p=0.0001) diet and phase II diet (-34.7%; p=0.0001). TG levels increased on both the MF (1.0%) and HF (5.5%) diets, although neither was statistically significant. People following the phase I and II diets showed reductions of 37.3% and 36.9%, respectively. Ho levels increased by 9.7% when people followed the MF diet and by 12.4% when they followed the HF diet. Patients following the phase I and phase II diets showed reductions of 13.6% and 14.6%, respectively. Only those following phase II diets showed a tendency toward significant improvement (p=0.061). Lp(a) levels increased by 4.7% following the MF (NS) diet and by 31.0% (NS) on the HF diet. Patients following phase I showed a 7.4% (NS) reduction and a 10.8% reduction (NS) following phase II. Fibrinogen levels increased only in individuals following HF diets (11.9%), while patients following MF (-0.6%), phase I (-11.0%), and phase II (-6.3%) diets showed nonsignificant reductions in fibrinogen. Patients on MF demonstrated nonsignificant reductions in weight, LDL-C, TC, HDL-C, TC/HDL-C ratios, and fibrinogen and nonsignificant increases in TGs, Lp(a), and homocysteine. There was significant weight loss in patients on phase I and II and HF diets after 1 year. Reductions in TC, LDL-C, TGs, and TC/HDL ratios were significant only in patients either following a LF diet or a MF, calorically reduced diet. Only patients following HF diets showed a worsening of each cardiovascular disease risk factor (LDL-C, TG, TC, HDL-C, TC/HDL ratio, Ho, Lp(a), and fibrinogen), despite achieving statistically significant weight loss.


The shared and contrasting roles of IL2 and IL15 in the life and death of normal and neoplastic lymphocytes: implications for cancer therapy.
IL2 and IL15, members of the 4α-helix bundle family of cytokines, play pivotal roles in the control of the life and death of lymphocytes. Although their heterotrimeric receptors have two receptor subunits in common, these two cytokines have contrasting roles in adaptive immune responses. The unique role of IL2 through maintenance of fitness of regulatory T cells and activation-induced cell death is the elimination of self-reactive T cells to prevent autoimmunity. In contrast with IL2, IL15 is dedicated to the prolonged maintenance of memory T-cell responses to invading pathogens. Blockade of IL2 and IL15 using monoclonal antibodies has been reported to be of value in the treatment of patients with leukemia, autoimmune disorders, and in the prevention of allograft rejection. IL2 has been approved by the FDA for the treatment of patients with malignant renal cell cancer and metastatic malignant melanoma. Clinical trials involving recombinant human IL15 given by bolus infusions have been completed, and studies assessing subcutaneous and continuous intravenous infusions are under way in patients with metastatic malignancy. Furthermore, clinical trials are being initiated that employ the combination of IL15 with IL15Rα(+/-) IgFc.


Three diagnostic psychiatric subgroups in comparison to self-stigma, quality of life, disorder severity and coping management cross-sectional outpatient study.
Much attention has been paid to psychological factors influencing characteristics, severity, and course of mental disorders. The objective of our investigation was to examine the interrelations among quality of life (QoL), self-stigma, and coping strategies, demographics and severity of the disorder in neurotic spectrum disorders, schizophrenia, and depressive spectrum disorders. A total of 343 clinically stable Czech outpatients with different mental disorders (153 with neurotic spectrum disorders; 81 with depression, and 109 with schizophrenia spectrum disorders) were included. The patients were examined by their outpatient psychiatrists during regular psychiatric checkup and completed a sociodemographic questionnaire, the Quality of Life Satisfaction and the Enjoyment Questionnaire (Q-LES-Q), the Internalized Stigma of Mental Illness Scale (ISMI), the Stress Coping Style Questionnaire (SVF-78), and the Clinical Global Impression scale (CGI). The study demonstrates that the self-stigma and coping strategies are significant factors linked to the QoL in all diagnostic groups of patients. Patients with schizophrenia spectrum disorders had lower scores in QoL compared to the other two groups. The patients with depression or neurotic spectrum disorders had a lesser degree of self-stigma than the patients with schizophrenia spectrum disorders. The severity of the illness significantly correlated with the QoL, self-stigma, and coping strategies. The investigation confirmed the connection between the quality of life, self-stigma, coping strategies, and the severity of the illness, in outpatients with schizophrenia spectrum disorders, depressive, and neurotic spectrum disorders. A further longitudinal study would be useful to determine the causative relationships of these variables.


Menstrual cycle phase does not affect whole body peak fat oxidation rate during a graded exercise test.
Female sex hormones fluctuate in a predictable manner throughout the menstrual cycle in eumenorrheic women. In studies conducted in both animal and humans, estrogen and progesterone have been found to exert individual metabolic effects during both rest and exercise, suggesting that estrogen may cause an increase in fat oxidation during exercise. However, not all studies find these metabolic changes with the natural physiological variation in the sex hormones. To date, no studies have investigated whether whole body peak fat oxidation rate (PFO) and maximal fat oxidation intensity (FATmax) are affected at different time points [mid-follicular (MF), late-follicular (LF), and mid-luteal (ML)] in the menstrual cycle, where plasma estrogen and progesterone are either at their minimum or maximum. We hypothesized that an increased plasma estrogen concentration together with low progesterone concentration in LF would result in a modest but significant increase in PFO. We found no differences in body weight, body composition, or peak oxygen uptake (V̇o2peak) between any of the menstrual phases in the 19 healthy, young eumenorrheic women included in this study. PFO [MF: 0.379 (0.324-0.433) g/min; LF: 0.375 (0.329-0.421) g/min; ML: 0.382 (0.337-0.442) g/min; mean ± (95% CI)] and resting plasma free fatty acid concentrations [MF: 392 (293-492) µmol/l; LF: 477 (324-631) µmol/l; ML: 396 (285-508) µmol/L] were also similar across the menstrual cycle phases. Contrary to our hypothesis, we conclude that the naturally occurring fluctuations in the sex hormones estrogen and progesterone do not affect the whole body PFO and FATmax in young eumenorrheic women measured during a graded exercise test.NEW & NOTEWORTHY Menstrual cycle phase does not affect the peak fat oxidation rate during a graded exercise test. Natural physiological fluctuations in estrogen do not increase peak fat oxidation rate. FATmax is not influenced by menstrual cycle phase in healthy, young eumenorrheic women.


Decision regret up to 6 years after sleeve gastrectomy.
Sleeve gastrectomy (SG) is one of the most popular types of weight loss surgery today but is neither risk-free nor universally effective. We previously demonstrated that 5% of Roux-en-Y gastric bypass (RYGB) patients and up to 20% of gastric banding patients report overall regret 4 years after surgery. This study explores patients' attitudes toward their decision to have SG and decision regret rates up to 6 years postoperatively. We surveyed 185 patients who were at least 6 months post-SG (response rate 30%). We used a modified version of the Decision Regret Scale developed by Brehaut et al. We converted responses to a 0-100 scale so that higher scores (> 50) reflect greater regret. We characterized patients who expressed having overall decision regret (score > 50) vs. those who did not (≤ 50). Demographic and preoperative clinical information was extracted from the online medical records. Of 185 SG patients, only 13 (7%) reported regret scores > 50 (i.e. high decision regret). Mean time from SG to survey completion was 41 months (range 6-76 months). Unadjusted comparisons between the two groups revealed that patients with high regret scores had lower mean weight loss (32.1% vs. 48.9% EBMIL), and reported less improvement in quality-of-life (QoL), such as physical health (46.2% vs. 93.5% "somewhat" or "significantly" improved). The two groups were similar in short-term complications, but those reporting overall regret were more likely to report GI complaints such as bloating (61.5% vs. 30.4%). Finally, patients with regret scores > 50 were more likely to be further out from SG (median time since surgery 61.8 vs. 41.1 months). In our study, very few patients reported regret (7%) up to 6 years postoperatively, in line with prior reports after RYGB. Those with regret reported poorer QoL.


Association Between Knee Osteoarthritis and Functional Changes in Ankle Joint and Achilles Tendon.
Increasing evidence has shown that biomechanical forces often drive the progression of knee osteoarthritis (OA). Attention should be given to the changes in adjacent joints and their relation to knee OA. The purpose of the present study was to examine the changes in Achilles tendon thickness of individuals with knee OA and to evaluate the correlation between Achilles tendon thickness and knee OA severity in a case-control prospective observational study. A total of 93 participants with no previous ankle injuries were recruited. Of the 93 participants, 63 had knee OA of the medial compartment and 30 served as controls. The subjects underwent a clinical examination that included measurements of weight, height, Achilles tendon thickness, and 1-leg heel rise. The subjects also underwent a computerized gait test and completed the Hebrew version of the Western Ontario and McMaster Osteoarthritis Index and 36-item short-form (SF-36) health survey. Significant difference was found in Achilles tendon thickness between the subjects with knee OA and the healthy controls (17.1 ± 3.4 versus 15.1 ± 3.1; p = .009). Significant differences were also found between the 2 groups in the 1-leg heel rise test, Western Ontario and McMaster Osteoarthritis Index scores, SF-36 scores, and all gait measures. Significant correlations were found between the Achilles tendon thickness and the following measures: weight (r = 0.46), body mass index (r = 0.55), Kellgren and Lawrence OA severity grade (r = 0.25), 1-leg heel rises (r = -0.50), and SF-36 score (r = -0.25). Subjects with knee OA presented with a thicker Achilles tendon compared with the healthy controls. Furthermore, a significant correlation between Achilles tendon thickness and knee OA severity was found. A comprehensive assessment of the Achilles tendon and ankle joint should be a part of the knee OA evaluation process.


Thermocatalytic Hydrogen Production Through Decomposition of Methane-A Review.
Consumption of fossil fuels, especially in transport and energy-dependent sectors, has led to large greenhouse gas production. Hydrogen is an exciting energy source that can serve our energy purposes and decrease toxic waste production. Decomposition of methane yields hydrogen devoid of COx components, thereby aiding as an eco-friendly approach towards large-scale hydrogen production. This review article is focused on hydrogen production through thermocatalytic methane decomposition (TMD) for hydrogen production. The thermodynamics of this approach has been highlighted. Various methods of hydrogen production from fossil fuels and renewable resources were discussed. Methods including steam methane reforming, partial oxidation of methane, auto thermal reforming, direct biomass gasification, thermal water splitting, methane pyrolysis, aqueous reforming, and coal gasification have been reported in this article. A detailed overview of the different types of catalysts available, the reasons behind their deactivation, and their possible regeneration methods were discussed. Finally, we presented the challenges and future perspectives for hydrogen production via TMD. This review concluded that among all catalysts, nickel, ruthenium and platinum-based catalysts show the highest activity and catalytic efficiency and gave carbon-free hydrogen products during the TMD process. However, their rapid deactivation at high temperatures still needs the attention of the scientific community.


Serum angiotensin-converting enzyme and blood monocytes in splenectomized individuals.
In 45 splenectomized individuals without malignancies, residual splenic tissue was detected by 99mTc-scanning using reinjection of labelled heat-damaged and autologous erythrocytes. The angiotensin-converting enzyme in serum (SACE) and the blood monocyte count were measured in order to demonstrate an eventual association between these parameters as well as the influence of residual splenic tissue. In 20 patients with detectable spleen tissue SACE was normal (26.2 +/- 4.4 U/ml), but in 25 patients without residual spleen tissue SACE was slightly elevated (28.7 +/- 6.4 U/ml; p less than 0.02) as compared with healthy controls (24.4 +/- 6.2 U/ml). In both groups of patients blood monocytes were markedly increased. However, no correlation could be demonstrated between SACE and the monocyte count in any group. In 2 patients SACE was above the upper limit of the normal range (greater than 36.8 U/ml) as found in sarcoidosis but no signs of this disease could be demonstrated. It is concluded that splenectomy must be taken into account when the significance of raised SACE is evaluated. It may be suggested that the spleen exerts an effect on the metabolism of SACE or on the ACE-producing cells in the organism.


Oxidized Substrates of APEH as a Tool to Study the Endoprotease Activity of the Enzyme.
APEH is a ubiquitous and cytosolic serine protease belonging to the prolyl oligopeptidase (POP) family, playing a critical role in the processes of degradation of proteins through both exo- and endopeptidase events. Endopeptidase activity has been associated with protein oxidation; however, the actual mechanisms have yet to be elucidated. We show that a synthetic fragment of GDF11 spanning the region 48-64 acquires sensitivity to the endopeptidase activity of APEH only when the methionines are transformed into the corresponding sulphoxide derivatives. The data suggest that the presence of sulphoxide-modified methionines is an important prerequisite for the substrates to be processed by APEH and that the residue is crucial for switching the enzyme activity from exo- to endoprotease. The cleavage occurs on residues placed on the C-terminal side of Met(O), with an efficiency depending on the methionine adjacent residues, which thereby may play a crucial role in driving and modulating APEH endoprotease activity.


Construct validity of the PROMIS® sexual function and satisfaction measures in patients with cancer.
With data from a diverse sample of patients either in treatment for cancer or post-treatment for cancer, we examine inter-domain and cross-domain correlations among the core domains of the Patient-Reported Outcomes Measurement Information System Sexual Function and Satisfaction measures (PROMIS® SexFS) and the corresponding domains from conceptually-similar measures of sexual function, the International Index of Erectile Function and the Female Sexual Function Index. Men (N=389) and women (N=430) were recruited from a tumor registry, oncology clinics, and an internet panel. The PROMIS SexFS, International Index of Erectile Function, and Female Sexual Function Index were used to collect participants' self-reported sexual function. The domains shared among the measures include desire/interest in sexual activity, lubrication and vaginal discomfort/pain (women), erectile function (men), orgasm, and satisfaction. We examined correlations among different domains within the same instrument (discriminant validity) and correlations among similar domains measured by different instruments (convergent validity). Correlations demonstrating discriminant validity ranged from 0.38 to 0.73 for men and 0.48 to 0.74 for women, while correlations demonstrating convergent validity ranged from 0.62 to 0.83 for men and 0.71 to 0.92 for women. As expected, correlations demonstrating convergent validity were higher than correlations demonstrating discriminant validity, with one exception (orgasm for men). Construct validity was supported by convergent and discriminant validity in a diverse sample of patients with cancer. For patients with cancer who may or may not have sexual dysfunction, the PROMIS SexFS measures provide a comprehensive assessment of key domains of sexual function and satisfaction.


Comparison of recombinant barramundi and human insulin-like growth factor (IGF)-I in juvenile barramundi (Lates calcarifer): in vivo metabolic effects, association with circulating IGF-binding proteins, and tissue localisation.
The in vivo actions of human and fish insulin-like growth factor (IGF)-I have been compared to extend the understanding of the metabolism of IGFs in fish and to identify potential differences in their actions. The effects of acute administration of these proteins on the incorporation of glucose into muscle glycogen and leucine into liver protein in juvenile barramundi were investigated. In these in vivo metabolic assays, both baramundi IGF-I (bIGF-I) and human IGF-I (hIGF-I) increase the incorporation of D-[14C]glucose into muscle glycogen and [14C]leucine into liver protein. The distribution of radio-labeled human and barramundi IGF-I in the circulation and their uptake by tissue was also compared in juvenile barramundi (Lates calcarifer). Analysis of trichloroacetic acid-precipitable radioactivity in sequential samples following bolus injection of radiolabeled IGFs revealed that hIGF-I was degraded faster than bIGF-I. Neutral gel chromatography of these samples suggested that this difference is due to reduced affinity of hIGF-I, compared to bIGF-I, for the IGF-binding proteins (IGFBPs) present in the barramundi. Tissue uptake of [125I]-labeled hIGF-I and bIGF-I was similar except that [ 125I]bIGF-I uptake by the kidney exceeded that of hIGF-I. It is suggested that while some of the in vivo actions of IGFs in fish are conserved, functional differences between mammalian and teleostean IGFs exist, particularly with respect to their interactions with fish IGFBPs.


Tumor-associated macrophages correlate with response to epidermal growth factor receptor-tyrosine kinase inhibitors in advanced non-small cell lung cancer.
Our study investigated whether tumor-associated macrophages (TAMs) in advanced non-small cell lung cancer (NSCLC) are related to treatment response to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and may be a predictor of survival. Of 206 advanced NSCLC patients treated (first-line) with an EGFR-TKI at the study hospital from 2006 to 2009, 107 with adequate specimens for assessing CD68 immunohistochemistry as a marker of TAMs were assessed. After EGFR-TKI treatment, response was observed in 55 (51%) patients, and the median follow-up period was 13.5 months. Most TAMs were located in the tumor stroma (>95%) and positively costained with the M2 marker CD163. TAM counts were significantly higher in patients with progressive disease than in those without (p < 0.0001), a trend that remained in patients with known EGFR mutation status (n = 59) and those with wild-type EGFR (n = 20). High TAM counts, among other factors (e.g., wild-type EGFR), were significantly related to poor progression-free survival (PFS) and overall survival (OS) (all p < 0.0001 for TAMs). Multivariate Cox analyses showed that high TAM counts and EGFR mutations were both independent factors associated with PFS [odds ratio (OR), 8.0; 95% confidence interval (CI), 2.87-22.4; p = 0.0001 and OR, 0.03; 95% CI, 0.003-0.31; p = 0.003, respectively] and OS (OR, 2.641; 95% CI, 1.08-6.5; p = 0.03 and OR, 0.14; 95% CI, 0.03-0.56; p = 0.006, respectively). TAMs are related to treatment response irrespective of EGFR mutation and can independently predict survival in advanced NSCLC treated with an EGFR-TKI.


Hydrazine Detection during Ammonia Electro-oxidation Using an Aggregation-Induced Emission Dye.
Ammonia electro-oxidation is an extremely significant reaction with regards to the nitrogen cycle, hydrogen economy, and wastewater remediation. The design of efficient electrocatalysts for use in the ammonia electro-oxidation reaction (AOR) requires comprehensive understanding of the mechanism and intermediates involved. In this study, aggregation-induced emission (AIE), a robust fluorescence sensing platform, is employed for the sensitive and qualitative detection of hydrazine (N2H4), one of the important intermediates during the AOR. Here, we successfully identified N2H4 as a main intermediate during the AOR on the model Pt/C electrocatalyst using 4-(1,2,2-triphenylvinyl)benzaldehyde (TPE-CHO), an aggregation-induced emission luminogen (AIEgen). We propose the AOR mechanism for Pt with N2H4 being formed during the dimerization process (NH2 coupling) within the framework of the Gerischer and Mauerer mechanism. The unique chemodosimeter approach demonstrated in this study opens a novel pathway for understanding electrochemical reactions in depth.


Student nurses' attitudes towards death and dying in south-east Iran.
In this study, the attitudes of student nurses from Kerman and Bam in Iran towards death and caring for dying patients were compared. Two types of questionnaire were used: the DAP-R (Death Attitude Profile Revised) and FATCOD (Frommelt Attitude Towards Caring for Dying patients). The Bam student nurses, who had more experience of death due to the Bam earthquake in December 2003, were found to be less afraid of death and also less likely to give care to people at the end of life compared to their counterparts in Kerman. In both groups, those who were educated about death and dying had more positive attitudes towards caring for people who are dying than non-educated participants. The study suggests that adding palliative care education, accompanied by a reflective narrative approach, to the nursing curriculum is necessary to improve quality of care at the end of life.