Primary retroperitoneal synovial sarcoma: a case report.
A case of a 36-yr-old woman with retroperitoneal synovial sarcoma is described. Her presenting symptom was epigastric pain that radiating to the back. On radiologic study, bulky retropancreatic soft tissue mass was detected which showed cystic and solid components. At operation, complete resection of the tumor was not possible because of the adhesion to the vena cava and the liver. During the follow-up, extensive tumor recurrence and liver metastasis were revealed. Primary retroperitoneal synovial sarcoma is a very rare malignant tumor with high mortality and recurrence rates. Retroperitoneal synovial sarcoma usually appears as a nonspecific soft tissue mass that do not have specific imaging features differentiating it from other mesenchymal tumors. However general radiologic findings and anatomic location of the tumor may help the diagnosis. In addition, synovial sarcoma should be included in the differential diagnosis of retroperitoneal soft tissue mass detected in young adults.


[Relationship between genetic polymorphism of MTHFR C677T and nonsyndromic cleft lip with or without cleft palate in Shanxi Province of China].
To assess the association between polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene C677T locus and nonsyndromic cleft lip with or without cleft palate (NSCL/P) in Shanxi Province of China. Blood samples from 150 patients and their parents and 150 controls and their mothers were collected. The polymorphism of MTHFR gene C677T locus were analyzed by the methods of polymerase chain reaction and restriction fragment length polymorphism technique(PCR-RFLP). Case-control analysis, transmission-disequilibrium test(TDT) and haplotype-based haplotype relative risk analysis(HHRR) were used to study the correlation between the gene mutation and NSCL/P. Hardy-Weinberg equilibrium test results showed that, the offspring and mother genotype in the case group and the control group was not deviated from the Hardy-Weinberg law of genetic equilibrium (P > 0.05). The distribution of genotype CC, CT and TT in offspring had significant difference between the two groups (P < 0.05). In the offspring and mother of case group and the control group, the carriers of the TT genotype compared to CC genotype, the OR are greater than 1 and 95% CI do not contain 1 (offspring OR: 2.692, 95% CI: 1.319-5.495; mother OR: 2.469, 95% CI: 1.136-5.363). The distribution of C allele and T mutation gene were significantly different in the offspring and mother between the two groups (P < 0.05). The TDT test showed: chi2 = 4.507, P < 0.05. The HHRR test showed: P < 0.05. The single nucleotide polymorphism of MTHFR C677T locus is associated with the development of NSCL/P in Shanxi Province.


A cell membrane modification technique using domain 4 of intermedilysin for immunotherapy against cancer.
Rapid cell membrane modification techniques are currently being sought in order to develop gene therapy and cellular immunotherapy modalities against cancer and other diseases. We developed a novel technique using the non-toxic portion of intermedilysin, a streptolysin O family cytolysin with a high affinity for human cell membranes, as a cell membrane adaptor module. Domain 4 recombinants of intermedilysin with linker sites at the N-terminus were designed. These modules are able to bind tightly to human cells after simple incubation and have no harmful effects. The modules were conjugated with the partially reduced or unreduced F(ab')2 of an anti-carcinoembryonic antigen monoclonal antibody. Erythrocytes bound to these conjugates were shown to specifically target a carcinoembryonic antigen-positive cell line, TT, in vitro. This is a promising technique for the development of convenient and effective anticancer treatment methods.


Inferior gluteal artery surgical access for embolization of large internal iliac artery aneurysm in a hostile abdomen.
Internal iliac artery aneurysms (IIAA) are a rare entity compared with all aortoiliac aneurysms. Continuous expansion due to retrograde flow from runoff vessels can lead to rupture with devastating results. Exclusion of the aneurysm represents a challenging procedure especially if the access is limited and the patient has a history of reoperations in the pelvic region. A 78-year-old man with a history of endovascular aortic repair, coverage of internal iliac arteries and right hemicolectomy for adenocarcinoma of ascending colon presented with a rapidly expanding right IIAA (8.8 cm) due to type II endoleak. He successfully treated with coil embolization through inferior gluteal artery surgical access. Inferior gluteal artery surgical access for embolization of internal iliac aneurysms in patients with hostile abdomen or in cases where antegrade route has already been excluded, is a feasible technique.


Persistent primitive hypoglossal artery associated with arteriovenous malformation--case report.
A case of persistent primitive hypoglossal artery (PPHA) associated with arteriovenous malformation (AVM) is reported. A 46-year-old male suddenly developed severe headache followed by transient unconsciousness and was admitted to our hospital 2 hours later. A computed tomographic scan showed subarachnoid hemorrhage. Angiograms revealed an AVM in the left cerebellar hemisphere and an ipsilateral PPHA. The AVM was completely removed and he was discharged 1 month after surgery without neurological deficit. Only three cases of PPHA associated with intracranial AVM have been reported in the literature. One patient died of rebleeding from the AVM before surgery, and another was conservatively treated because the AVM was too large for resection. The remaining one was surgically treated only by ligation of the feeding arteries. Ours is the first case treated by total removal of the AVM. Since these four cases, including ours, account for 3.0% of 134 cases of PPHA reported, PPHA associated with AVM is considered rare.


[A pharmacological study of the participation of the peripheral endings of primary afferent neurons in the inflammatory response evoked by heat and mechanical noxious stimulation].
To investigate the participation of neuropeptides present in the peripheral endings of primary afferent neurons in the inflammatory response, immunoreactive substance P (iSP), calcitonin gene-related peptide (iCGRP) and neurokinin A (iNKA) levels in the s.c. perfusate, and inflammatory response (edema and plasma protein extravasation) evoked in rat paw by noxious stimulation were determined. The effects of these peptides on plasma protein extravasation in the skin of the hind paw of mice were also examined with the pontamine sky blue protein labelling method. The following results were obtained. 1) Immersion of the rat hind paw for 30 min into hot water adjusted to 47 degrees C led to a marked increase in the release of iSP and iCGRP in the subcutaneous perfusate with the formation of thermal edema. 2) Mechanical stimulation (600 g, 10 min) to the hind paw or electrical stimulation of the saphenous and sciatic nerves (10 V, 2 Hz, 1msec duration, 10 min) evoked the increase of iSP release in the perfusate with plasma protein extravasation. 3) iNKA release was not affected by neither heat nor mechanical stimulation. 4) Intraplantar injection of SP, CGRP and NKA induced plasma protein extravasation, the order of potencies being SP greater than CGRP greater than NKA. The action of SP was antagonized by spantide, an SP antagonist. The injection of CGRP with SP produced a synergistic action on plasma protein extravasation. 5) Neonatal pretreatment with capsaicin, which is known to degenerate small-diameter primary afferent neurons, caused the decrease in amount of iSP and iCGRP released during noxious heat stimulation. 6) Pretreatment with Compound 48/80, or stem bromelain and emorphazone, or des-Arg9-[Leu8]-BK, inhibited the iSP release evoked by noxious heat stimulation. 7) Opioids such as morphine (mu-agonist) and ethylketocyclazocine (kappa agonist) inhibited the heat stimulus-evoked iSP release and thermal edema, and the inhibitory effects were antagonized by pretreatment with their antagonists. 8) Morphine or ethylketocyclazocine or [D-Ala2,D-Leu5]-enkephalin (delta-agonist) inhibited the release of iSP evoked by electrical stimulation of the saphenous and sciatic nerves. These results indicate that SP and CGRP present in peripheral endings of small-diameter primary afferent neurons play an important role in the inflammatory response, and that opioids are involved in the regulation of inflammatory response through the inhibition of SP release.


Regiospecific, enantiospecific total synthesis of C-19 methyl substituted sarpagine alkaloids dihydroperaksine-17-al and dihydroperaksine.
The optically active tetracyclic ketone 8 was converted into the pentacylic core 14 of the C-19 methyl substituted N(a)-H sarpagine and ajmaline alkaloids via a critical haloboration reaction. The ketone 14 was then employed in the total synthesis of 19(S),20(R)-dihydroperaksine-17-al (1) and 19(S),20(R)-dihydroperaksine (2). The key regioselective hydroboration and controlled oxidation-epimerization sequence developed in this approach should provide a general method to functionalize the C(20)-C(21) double bond in the ajmaline-related indole alkaloids.


[Inhibition of ovalbumin glycopeptides on the hCG signal transduction system].
Rat testicular cells dispersed by 0.03% collagenase digestion were seperated by discontinuous/continuous of Percoll, yielding highly pure Leydig cell fraction. 0.52 nmol/L hCG 0.1 mumol/L cholera toxin and 10 mumol/L forskolin signifcantly stimulated production of cAMP (Cholera toxin > Forskolin > hCG) and testosterone (no signifcient differences among cholera toxin, Forskolin and hCG). Ovalbumin glycopeptides prepared by extensive pronase digestion significantly inhibited production of cAMP and testosterone of rat testis Leydig cells stimulated by hCG, cholera toxin and forskolin. These results suggest that the carbohydrate moiety of hCG participate in the signal transduction among receptor, G-protein and adenylatecyclase which is inhibited by Asn-linked oligosaccharide chains from ovalbumin glycopeptides.


Prediction of chemotherapy response in untreated malignant lymphomas using technetium-99m methoxyisobutylisonitrile scan: comparison with P-glycoprotein expression and other prognostic factors. A preliminary peport.
The purpose of this study was to predict chemotherapy response in untreated malignant lymphomas using technetium-99m methoxyisobutylisonitrile (Tc-MIBI) scan. Twenty-five patients with malignant lymphoma were studied before receiving chemotherapy. Early Tc-MIBI scan was performed 10 min after intravenous injection of Tc-MIBI. Immunohistochemical analyses were performed on multiple non-consecutive sections of the biopsy specimens to determine Pgp expression. Chemotherapy response was evaluated in the first 1-2 years after completion of treatment by clinical and radiological methods. The mean tumor-to-background ratio of the 15 patients with good response (3.3 +/- 0.6) was significantly higher than that of the 10 patients with poor response (1.2 +/- 0.1). Among the 15 patients with good response to chemotherapy, all had positive Tc-MIBI scan results but negative Pgp expression. Among the 10 patients who had poor response to chemotherapy, all 10 had negative Tc-MIBI scan, but six patients had positive Pgp expression and four had negative Pgp expression. Significant differences were found in the incidences of good and poor responses determined by Tc-MIBI scan and Pgp expression. However, there were no significant differences in the incidences of good and poor responses for other prognostic factors. Compared with other prognostic factors, early Tc-MIBI scan more accurately predicts chemotherapy response in patients with malignant lymphoma.


Cysteinyl leukotriene levels correlate with 8-isoprostane levels in exhaled breath condensates of atopic and healthy children.
Cysteinyl leukotrienes are important mediators of airway inflammation, whereas 8-isoprostane is a biomarker of oxidative stress. This study evaluated the distributions of cysteinyl leukotriene and 8-isoprostane concentrations in exhaled breath condensates (EBCs) of children. The relationship between cysteinyl leukotriene and 8-isoprostane concentrations in the EBCs was also evaluated. The EBCs were collected from 34 children with allergic respiratory diseases and 24 healthy children. All recruited children underwent pulmonary function testing every season. The severity of allergic respiratory diseases and medication status were assessed every month in children with allergic respiratory diseases. The EBC cysteinyl leukotriene and 8-isoprostane levels were higher in children with asthma and allergic rhinitis than in those with asthma only and healthy children. In asthmatic children, cysteinyl leukotriene and 8-isoprostane levels peaked in the summer. All children showed a clear association between EBC cysteinyl leukotriene and EBC 8-isoprostane levels. The cysteinyl leukotriene and 8-isoprostane concentrations in the EBCs of children significantly varied by season. Oxidative stress correlated with airway inflammation in children.


Species differences in the expression of transforming growth factor-alpha (TGF-alpha) in the submandibular gland and pancreas.
Significant differences exist in the expression of transforming growth factor-alpha (TGF-alpha) in the submandibular glands (SMG) and the pancreas of different species and among cell components in the same species. Our previous studies have shown marked differences in the expression of TGF-alpha in the pancreas of humans and Syrian hamsters. To examine whether these differences also exist in other species, we examined the expression of TGF-alpha in the pancreas of mouse, rat, Syrian hamster, guinea pig, rabbit, pig, dog, and monkey. We included the SMG of these species for comparison. The formalin-fixed tissues of these species (n = 3) were investigated by immuno-histochemistry using a monoclonal antibody to TGF-alpha. The SMG of rat, mouse, hamster, rabbit, pig, dog, and monkey were examined by RT-PCR to assure the specificity of the antibody. Remarkable species differences were found in the expression of this peptide in both the SMG and the pancreas. In the SMG, the expression varied in different cell components, even in the same tissue of the species. Although excretory and secretory ducts of the SMG of most species reacted with the antibody, intercalated ducts were immunoreactive only in mouse and guinea pig. Acinar cells were either weakly positive or nonimmunoreactive. In the pancreas of most species, the cells of the large and medium-sized ducts expressed TGF-alpha, whereas centroacinar cells of only rat and dog reacted with the antibody. Marked differences were found in the expression of TGF-alpha in islet cells and in its spatial distribution. Differences were also found in the immunoreactivity of mesenchymal and neural cells among the species.


Composition controlled synthesis and Raman analysis of Ge-rich Si(x)Ge(1-x) nanowires.
Here, we report the synthesis of Si(x)Ge(1-x) nanowires with x values ranging from 0 to 0.5 using bulk nucleation and growth from larger Ga droplets. Room temperature Raman spectroscopy is shown to determine the composition of the as-synthesized Si(x)Ge(1-x) nanowires. Analysis of peak intensities observed for Ge (near 300 cm(-1)) and the Si-Ge alloy (near 400 cm(-1)) allowed accurate estimation of composition compared to that based on the absolute peak positions. The results showed that the fraction of Ge in the resulting Si(x)Ge(1-x) alloy nanowires is controlled by the vapor phase composition of Ge.


Differentiation between hemangiomas and metastases of the liver with ultrafast MR imaging: preliminary results with T2 calculations.
We studied the efficacy of T2 measurements at high field strength in distinguishing between liver hemangiomas and hepatic metastases when an ultrafast (single-excitation) MR imaging technique is used. Fourteen patients with known liver tumors were imaged in a 2.0-T prototype ultrafast MR scanner with a spin-echo (infinite TR and TE of 30-340 msec) pulse sequence. Each image was obtained with a total data acquisition time of 20 msec. T2 calculations for hepatic metastases (n = 6) showed a mean of 79.3 +/- 13.5 msec, whereas hemangiomas (n = 8) showed a T2 of 139.8 +/- 18.8 msec (p less than .0001). T2 values of lesions had a smaller relative standard deviation than previously reported, and the range of T2 values of hemangiomas (119-181 msec) and metastases (68-103 msec) did not overlap. Our preliminary results suggest that T2 calculations with ultrafast MR imaging may be useful for differentiating hemangiomas from metastases. We hypothesize that T2 values obtained from ultrafast MR images are more reliable than those obtained from conventional MR images, primarily because of the elimination of T1 information and effects of motion on image signal intensity.


Ferromagnetic planar Josephson junction with transparent interfaces: a φ junction proposal.
We calculate the current-phase relation of a planar Josephson junction with a ferromagnetic weak link located on top of a thin normal metal film. Following experimental observations we assume transparent superconductor-ferromagnet interfaces. This provides the best interlayer coupling and a low suppression of the superconducting correlations penetrating from the superconducting electrodes into the ferromagnetic layer. We show that this Josephson junction is a promising candidate for experimental φ junction realization.


Family Structure, Family Stability, and Outcomes of Five-Year-Old Children.
This study exploits data from the Fragile Families and Child Wellbeing Study, a birth cohort study of a diverse sample of children from twenty U.S. cities (N = 3,676), to examine how cognitive, behavioural, and health outcomes of five-year old children differ according to their family structure and family stability. We define three models: one that measures family structure at birth only, a second that measures current family structure at year five conditional on family structure at birth, and a third that measures changes in family structure from birth to age five. We find that while family structure has persistent links to child outcomes, the effects are significantly altered by stability of the family structure over time. These findings remain robust even after addressing selection.


Direct evidence for catalase activity of [Ru(V)(edta)(O)](-).
Reported is the first example of a ruthenium(III) complex, Ru(III)(edta) (edta(4-) = ethylenediaminetetraacetate), that catalyzes the disproportion of H2O2 to O2 and water in resemblance to catalase activity, and shedding light on the possible mechanism of action of the [Ru(V)(edta)(O)](-) formed in the reacting system.


A socio-ecological approach to understanding barriers to prenatal care for women of low income.
This paper critically examines the notion of barriers as conceptualized in the literature and suggests an expanded orientation to more fully appreciate its complexity. This alternative approach not only takes into account factors and processes relevant to the individual that create constraints to utilization, but also acknowledges influences on the design and delivery of health care. These latter considerations determine the availability and characteristics of programmes and services that may or may not encourage or enable participation by persons of low income. A socio-ecological model is proposed that compels health care practitioners and researchers to acknowledge the many influences on utilization behaviour. The literature on barriers to prenatal care is subsequently reviewed and evaluated, with consideration given to the range of behavioural determinants suggested by the model. Finally, a case is made for qualitative methods for inquiry to further enhance knowledge about factors and processes influencing use of the health care system, including prenatal care. It is argued that these approaches lead to enhanced appreciation of behaviour as a social product and are consistent with the ideology of health promotion.


A Dermatopathologist's Guide to Troubleshooting Immunohistochemistry Part 1: Methods and Pitfalls.
Immunohistochemistry (IHC) is a method by which specific target antigens can be detected in formalin-fixed paraffin-embedded tissue and involves the use of monoclonal or polyclonal antibodies; visualization of specific tissue antigens is achieved through an enzymatic reaction that transforms a colorless chromogen to a colored one. These enzymes may be attached to the antibody through a protein-ligand method (eg, biotin-avidin or biotin-streptavidin) or through a secondary antibody. Epitopes that are masked by protein linkage during formalin fixation are unmasked using a retrieval system that either uses heat (heat-induced epitope retrieval) or proteolytic enzymes (proteolytic-induced epitope retrieval). Part 1 of this review will focus and elaborate on the available methodologies for IHC testing, common problems inherent to each technique, and how they can be resolved. Part 2 will focus on common problems and artifacts encountered during IHC staining, likely causes, and methods for addressing each problem.


[Long-term clinical effects of preoperative radiotherapy on anal function after intersphincteric resection].
The aim of this study was to determine whether preoperative radiotherapy had an influence on the anal function of patients having an intersphincteric resection (ISR). We evaluated a long-term outcome and postoperative anal function in 22 patients having undergone ISR for low rectal cancer. There was no significant difference between the irradiated and nonirradiated group in the postoperative complications and oncological outcome. After a median follow-up of 6 .8 years, the number of bowel movements per 24 hours in patients with and without radiation was 4 .5 and 2 .7, respectively. Poor anal function assessed by Wexner incontinence score and Kirwan classification were significantly associated with preoperative radiotherapy. Preoperative radiotherapy was identified as a risk factor with the greatest negative impact on anal function after ISR.


A new large species of Myloplus (Characiformes, Serrasalmidae) from the Rio Madeira basin, Brazil.
Myloplus zorroi sp. n. is described from the Rio Madeira Basin in Amazonia. The new species had been treated as an undescribed Tometes species because of the absence of a marked abdominal keel and few small spines forming its prepelvic serrae, features commonly found in the species of the Myleus clade of the Serrasalmidae (species of genera Myleus, Mylesinus, Ossubtus and Tometes) and also in species of Utiaritichthys. Myloplus zorroi sp. n. shares the following characters with its congeners and Utiaritichthys: molariform teeth (versus incisiform teeth in Myleus clade members); a labial row of premaxillary teeth separated from lingual row by an internal gap (versus absence of internal gap between premaxillary teeth rows); and an ascending process of premaxilla wide from its base to the tip (versus ascending process tapering from its base to the tip). Like other Myloplus species, Myloplus zorroi sp. n. differs from Utiariticthys by having a deeper body, approximately 60% of standard length (versus usually less than 50% of standard length). Considering all the morphological evidence, including the presence of 13-19 low spines forming the prepelvic serrae in Myloplus zorroi sp. n. versus more than 20 high spines forming a marked prepelvic keel in other species of Mylopus, the new species is here assigned to Myloplus. Comparisons of the new species with nominal species of Myloplus, representatives of the Myleus clade, and other related taxa are provided.


Totally endoscopic coronary artery bypass grafting on cardiopulmonary bypass with robotically enhanced telemanipulation: report of forty-five cases.
Robotically enhanced telemanipulation is a new powerful tool for minimally invasive procedures that allows totally endoscopic cardiac surgery. Between June 1999 and February 2001, 45 robotically enhanced totally endoscopic coronary artery bypass grafting procedures on the arrested heart were performed at our institution with the use of the da Vinci telemanipulation system (Intuitive Surgical, Inc, Mountain View, Calif). In 37 patients a single-vessel totally endoscopic coronary bypass operation was performed. Eight patients had different types of multivessel revascularization with both internal thoracic arteries. The initial conversion rate was 22% and dropped to 5% in the last 20 patients. Two patients required reexploration via median sternotomy. The first 22 patients had excellent graft patency on discharge. The procedural time for single-vessel totally endoscopic bypass was 4.2 +/- 0.4 hours, bypass time was 136 +/- 11 minutes, and aortic crossclamp time amounted to 61 +/- 5 minutes. The present data show the feasibility of closed chest single- and double-vessel revascularization, with good clinical results. However, procedural time is prolonged and the complex endoscopic and endoaortic occlusion techniques, as well as the extensive anesthesiologic monitoring, are demanding. The need for conversion to an open procedure diminished after a relatively short learning curve. All postulated benefits of totally endoscopic surgery other than excellent cosmesis must be evaluated in larger cohorts.


Palliative and end-of-life care in lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.
In the United States, lung cancer is a major health problem that is associated with significant patient distress and often limited survival, with some exceptions. The purpose of this article is to address the role of palliative and end-of-life care in the management of patients with lung cancer and to address the need for good communication skills to provide support to patients and families. This article is based on an extensive review of the medical literature up to April 2012, with some articles as recent as August 2012. The authors used the PubMed and Cochrane databases, as well as EBESCO Host search, for articles addressing palliative care, supportive care, lung neoplasm, and quality of life in cancer or neoplasm, with no limitation on dates. The research was limited to human studies and the English language. There was no "definitive" work in this area, most of it being concurrence based rather than evidence based. Several randomized controlled trials were identified, which are reviewed in the text. The article focuses on the assessment and treatment of suffering in patients with lung cancer, as well as the importance of communication in the care of these patients over the course of the disease. The aim of medical care for patients with terminal lung cancer is to decrease symptom burden, enhance the quality of remaining life, and increase survival benefit. A second objective is to emphasize the importance of good communication skills when addressing the needs of the patient and his or her family, starting at the time of diagnosis, which in itself is a life-changing event. Too often we do it poorly, but by using patient-centered communication skills, the outcome can be more satisfactory. Finally, the article addresses the importance of advance care planning for patients with lung cancer, from the time of diagnosis until the last phase of the illness, and it is designed to enhance the physician's role in facilitating this planning process. This article provides guidance on how to reduce patient distress and avoid nonbeneficial treatment in patients with lung cancer. The goal is to decrease symptom burden, enhance quality of life, and increase survival benefit. Good communication and advance care planning are vital to the process.


Distinct signaling pathways after higher or lower doses of radiation in three closely related human lymphoblast cell lines.
The tumor suppressor p53 plays an essential role in cellular responses to DNA damage caused by ionizing radiation; therefore, this study aims to further explore the role that p53 plays at different doses of radiation. The global cellular responses to higher-dose (10 Gy) and lower dose (iso-survival dose, i.e., the respective D0 levels) radiation were analyzed using microarrays in three human lymphoblast cell lines with different p53 status: TK6 (wild-type p53), NH32 (p53-null), and WTK1 (mutant p53). Total RNAs were extracted from cells harvested at 0, 1, 3, 6, 9, and 24 h after higher and lower dose radiation exposures. Template-based clustering, hierarchical clustering, and principle component analysis were applied to examine the transcriptional profiles. Differential expression profiles between 10 Gy and iso-survival radiation in cells with different p53 status were observed. Moreover, distinct gene expression patterns were exhibited among these three cells after 10 Gy radiation treatment, but similar transcriptional responses were observed in TK6 and NH32 cells treated with iso-survival radiation. After 10 Gy radiation exposure, the p53 signaling pathway played an important role in TK6, whereas the NFkB signaling pathway appeared to replace the role of p53 in WTK1. In contrast, after iso-survival radiation treatment, E2F4 seemed to play a dominant role independent of p53 status. This study dissected the impacts of p53, NFkB and E2F4 in response to higher or lower doses of gamma-irradiation.


Endings and the end of treatment bell in paediatric cancer treatment for acute lymphoblastic leukaemia: An interpretative phenomenological analysis of children's perspectives.
Advancements in paediatric oncology have made quality of life after cancer increasingly clinically important. Little is currently known about children's experiences of treatment completion and its management. The current study explores children's experience of ending treatment for Acute Lymphoblastic Leukaemia (ALL), and the meaning it is given, particularly how endings are signified and marked. Semi-structured interviews were conducted with seven children who had completed cancer treatment for ALL with good prognoses. Interviews were analysed using Interpretative Phenomenological Analysis. Five superordinate themes were generated: 'the end is always there', 'the punctuation of endings', 'that which is remembered, that which is forgotten', 'the voiced and the unvoiced', and 'freedom from cancer.' Children highlighted the importance of punctuating and celebrating the end of their treatment, and the need for doing this in ways that helped them process the complexity of ending active treatment and provides space for their voices.


Efficiency of hydroxyl radical formation and phenol decomposition using UV light emitting diodes and H2O2.
A novel process combining hydrogen peroxide (H2O2) and radiation emitted by ultraviolet light emitting diodes (UV LEDs) has been investigated. The UV LEDs were used as UV-C light sources emitting radiation in the range 257-277 nm for decomposition of the model substance phenol in water. In addition, the effect of H2O2 to phenol molar ratio and initial phenol concentration was examined. Two parameters, the decomposition efficiency of phenol and characterization of hydroxyl radical (HO*) production from H2O2 when illuminated with UV radiation, were selected to provide detailed information regarding the performance of the UV LEDs in the treatment process. A new concept was introduced to characterize and describe the production of HO* radicals produced when photons were absorbed by H2O2 molecules. The phenol decomposition efficiency at the initial concentration of 100 mg/L was the most pronounced at the lowest emitted wavelength. A significant correlation was found between the phenol decomposition efficiency and the photons absorbed by H2O2 (i.e. formation of radicals).


A Randomized Controlled Trial Protocol for Using an Accelerometer-Smartphone Application Intervention to Increase Physical Activity and Improve Health among Employees in a Military Workplace.
Physical activity is beneficial for improving health and reducing sick leave absences. This article describes a protocol for an intervention using an interactive accelerometer smartphone application, telephone counselling, and physical activity recordings to increase the physical activity of workers in the military and improve their health. Under the protocol, employees from six military brigades in Finland will be randomly assigned to intervention and control groups. The intervention group's participants will use accelerometers to measure their daily physical activities and their quality of sleep for six months. They will receive feedback based on these measurements via a smartphone application. The intervention group's participants will be encouraged to exercise for two hours per week during working hours, and to participate in telephone counselling. The control group's participants will continue with their normal exercise routines, without the accelerometer or feedback. The participants of both groups will be measured at the baseline, after the intervention period, and six months after the end of the intervention. The measurements will include accelerometer recordings, biochemical laboratory tests, body composition measurements, physical fitness tests, and questionnaires on sociodemographic factors, physical activities, and health. The primary outcomes will indicate changes in physical activity, physical fitness, and sick leave absences. The findings will help to develop a straightforward and cost-effective model for supporting the health and working capabilities of employees in the military and other workplaces.


Chromatin architecture, CCCTC-binding factor, and V(D)J recombination: managing long-distance relationships at antigen receptor loci.
The rearrangement of T and B lymphocyte Ag receptor loci occurs within a highly complex chromosomal environment and is orchestrated through complex mechanisms. During the past decade, a large body of literature has highlighted the significance of chromatin architecture at Ag receptor loci in supporting the genomic assembly process: in preparation for recombination, these loci tend to contract and form multiple loops that shorten the distances between gene segments and facilitate recombination events. CCCTC-binding factor, CTCF, has received much attention in this regard since it has emerged as an important regulator of chromatin organization and transcription. In this review, we summarize recent work outlining conformational dynamics at Ag receptor loci during lymphocyte development and we discuss the role of CTCF in Ag receptor locus conformation and repertoire development.


Clustering of Obesity-Related Risk Behaviors Among Families With Preschool Children Using a Socioecological Approach: Cross-Sectional Study.
Limited attention has been given to assessing home environments of parents with preschool-aged children using a socioecological approach to better understand potential influencers of obesity risk. The purpose of this cross-sectional study was to examine the clustering of obesity-related risk behaviors among mothers with preschool children. Mothers with preschool-aged children (ages 2 to 5 years) who participated in the online Home Obesogenic Measure of Environments (HOMES) survey were examined in clustering of four healthy recommended behaviors (ie, mother's fruit and vegetable intake ≥5 per day, sedentary screen time <4 hours per day, sugar-sweetened beverage intake <1 time/day, and increased physical activity level). Frequencies and percents of the clustering variables were conducted along with Spearman rank order correlations to determine significant associations. Ward's method with squared Euclidean distances were performed for the cluster analysis using the four standardized continuous variables. Identification of total cluster number was determined by visually inspecting the dendogram. Sociodemographic, intrapersonal, social environment, and home physical environment characteristic differences between cluster groups were further examined by independent t tests and chi-square analysis to validate findings. Of the 496 participants (72.6%, 360/496 white; age mean 32.36, SD 5.68 years), only a third (37.1%, 184/496) consumed five or more servings of fruits/vegetables daily, had low sedentary screen time of <4 hours/day, and reported moderate to high levels of physical activity (34.1%, 169/496). More than half (57.7%, 286/496) consumed <1 sugar-sweetened beverage serving daily. A positive correlation (r=.34, P<.001) between physical activity level and fruit/vegetable intake (≥5 servings/day), and a positive correlation (r=.15, P=.001) between low sedentary screen time (<4 hours/day) and low sugar-sweetened beverage intake (<1 serving/day) were found. Ward's hierarchical analysis revealed a two-cluster solution: less healthy/inactive moms (n=280) and health conscious/active moms (n=216). Health conscious/active moms were significantly (P<.010) likely to be more physically active, have lower sedentary screen time, lower daily intake of sugar-sweetened beverages, and greater daily intake of fruits and vegetables compared to less healthy/inactive moms. Less healthy/inactive moms were significantly more likely to have a higher body mass index and waist circumference compared to the other cluster; however, there were no significant sociodemographic differences. There were many intrapersonal (eg, importance of physical activity for child and self) and home physical environment (eg, home availability of fruits/vegetables and salty/fatty snacks) characteristic differences between clusters, but few significant differences emerged for social environment characteristics (eg, family meals, family cohesion). Findings may have implications in tailoring future obesity prevention interventions among families with young children.


Proteolytic processing, axonal transport and differential distribution of chromogranins A and B, and secretogranin II (secretoneurin) in rat sciatic nerve and spinal cord.
The chromogranin family comprises chromogranin A and B, and secretogranin II. The present study has focused on the axonal transport of chromogranins/secretogranin II and their detailed distribution in peripheral nerves and the spinal cord. With radioimmunoassay (RIA) and column chromatography, we first studied the processing of chromogranin B and secretogranin II during axonal transport. No larger precursors of these peptides were detected in the sciatic nerves, indicating that they are already processed to a high degree early during axonal transport. We also analysed nerve segments above and below a crush, using RIA, in order to compare these accumulation data with those obtained by the cytofluorimetric-scanning (CFS) technique. For the latter technique, the amounts of accumulation distal to the crush (presumably representing recycling and retrogradely transported peptides) were 30-40% of the amounts in the proximal accumulation for chromogranin A and secretoneurin, in contrast to chromogranin B, which showed 15% recycling. With the RIA, the corresponding values for secretoneurin and PE-11 (antibody against chromogranin B) were 42% and 14%, respectively. Therefore, the data obtained by CFS were in excellent agreement with those obtained by RIA. In crushed sciatic nerves, chromogranin A was present in large axons as well as in small- and medium-sized axons. Chromogranin B was mainly restricted to large axons, while secretoneurin was localized to bundles of small axons. This differential distribution was also found in the spinal roots and in the peripheral terminals. Chromogranin A was present in both ventral and dorsal roots, and chromogranin B was detected in ventral roots and in large sensory axons in the dorsal roots. Secretoneurin was dominant in the dorsal root. Double-labelling studies with antibodies against choline acetyltransferase/vesicular acetylcholine transporter, or against tyrosine hydroxylase, confirmed that chromogranin A was distributed in cholinergic, sensory, as well as adrenergic neurons. Chromogranin B was mainly present in cholinergic motor neurons and large sensory neurons, and secretoneurin was restricted to adrenergic and sensory neurons. The present study demonstrates that chromogranins A and B, and secretoneurin are transported with fast axonal transport in the peripheral nerves, with different amounts of recycling, and that they are differentially distributed in different types of neurons in the peripheral nervous system and the spinal cord, suggesting that each of them may play a special role in subsets of neurons.


The antiproliferative effect of somatostatin analogs: clinical relevance in patients with neuroendocrine gastro-entero-pancreatic tumours.
Somatostatin analogs (SSAs) have an important role in the management of patients with neuroendocrine tumours of the gastrointestinal tract and pancreas (GEP NETs). These compounds can control the symptoms induced by the production of hormones and peptides. The antiproliferative effects of SSAs and especially tumour shrinkage are less obvious in patients with GEP NETs than in those with acromegaly. However, based upon phase II experience there is a strong suggestion of a disease stabilizing effect of SSAs in selected patients. Those patients with a progressive, non-functional GEP NET, positive octreotide scintigraphy, a low proliferation index and in the absence of surgical options may benefit from a first-line medical therapy with SSAs. The exploration of the mechanisms of this effect are unclear and hampered by the lack of suitable preclinical models. The better understanding of the tumour biology of GEP NETs, together with the development of new SSAs with better affinity on all somatostatin receptors, represent an unmet medical need.


Non-cell-autonomous effects of Ret deletion in early enteric neurogenesis.
Neural crest cells (NCCs) form at the dorsal margin of the neural tube and migrate along distinct pathways throughout the vertebrate embryo to generate multiple cell types. A subpopulation of vagal NCCs invades the foregut and colonises the entire gastrointestinal tract to form the enteric nervous system (ENS). The colonisation of embryonic gut by NCCs has been studied extensively in chick embryos, and genetic studies in mice have identified genes crucial for ENS development, including Ret. Here, we have combined mouse embryo and organotypic gut culture to monitor and experimentally manipulate the progenitors of the ENS. Using this system, we demonstrate that lineally marked intestinal ENS progenitors from E11.5 mouse embryos grafted into the early vagal NCC pathway of E8.5 embryos colonise the entire length of the gastrointestinal tract. By contrast, similar progenitors transplanted into Ret-deficient host embryos are restricted to the proximal foregut. Our findings establish an experimental system that can be used to explore the interactions of NCCs with their cellular environment and reveal a previously unrecognised non-cell-autonomous effect of Ret deletion on ENS development.


Making sense of caregiving for persons with multiple sclerosis (MS): the dimensional structure of sense making and relations with positive and negative adjustment.
Sense making is a meaning-making process that refers to the development of explanations for adversity. Despite a growing interest in this construct within the chronic illness literature, it has been neglected in research on carers. This study examines the dimensional structure of a multi-item measure of sense making in carers of people with multiple sclerosis (MS) and investigates relations between sense making and both positive and negative adjustment outcomes. Participants were 232 carers and their care recipients. Questionnaires were completed at first assessment (time 1) and 12 months later (time 2). Factor analysis of the Carer Sense Making Scale (CSMS) revealed six psychometrically sound factors: catalyst for change, acceptance, spiritual perspective, incomprehensible, relationship ties, and causal attribution. Results of regression analyses indicated that the time 2 CSMS factors accounted for significant amounts of variance in each of the time 2 adjustment outcomes (life satisfaction, positive affect, anxiety, depression, care recipient adjustment ratings of carer) after controlling for time 1 adjustment and relevant demographic and illness variables. Findings delineate the dimensional structure of sense making in caregiving and the differential links between sense-making dimensions and adjustment, and have implications for the measurement of sense making.


Comparison of echocardiographic changes after short- and long-duration spaceflight.
Previous echocardiographic studies of astronauts before and after short-duration (4-17 d) missions have demonstrated a decrease in resting left ventricular stroke volume, but maintained ejection fraction (EF) and cardiac output. Similar studies before and after long-duration (129-144 d) spaceflight have been rare and their overall results equivocal. Echocardiographic measurements (M-mode, 2-D, and Doppler) were obtained from short-duration (n = 13) and long-duration (n = 4) crewmembers to evaluate cardiac chamber sizes and function. Compared with short-duration astronauts, long-duration crewmembers had decreases in EF (+6+/-0.02 vs. -10.5+/-0.03%, p = 0.005) and percent fractional shortening (+7+/-0.03 vs. -11+/-0.07%, p = 0.015), and an increase in left ventricular end systolic volume (-12+/-0.06 vs. +39+/-0.24%, p = 0.011). These data suggest a reduction in cardiac function that relates to mission duration. As the changes in BP and circulating blood volume are reported to be similar after short- and long-duration flights, the smaller EF after longer spaceflights may be due to a decrease in cardiac function rather than altered blood volume.


Microbial community gene expression within colonies of the diazotroph, Trichodesmium, from the Southwest Pacific Ocean.
Trichodesmium are responsible for a large fraction of open ocean nitrogen fixation, and are often found in complex consortia of other microorganisms, including viruses, prokaryotes, microbial eukaryotes and metazoa. We applied a community gene expression (metatranscriptomic) approach to study the patterns of microbial gene utilization within colonies of Trichodesmium collected during a bloom in the Southwest Pacific Ocean in April 2007. The survey generated 5711-day and 5385-night putative mRNA reads. The majority of mRNAs were from the co-occurring microorganisms and not Trichodesmium, including other cyanobacteria, heterotrophic bacteria, eukaryotes and phage. Most transcripts did not share homology with proteins from cultivated microorganisms, but were similar to shotgun sequences and unannotated proteins from open ocean metagenomic surveys. Trichodesmium transcripts were mostly expressed photosynthesis, N(2) fixation and S-metabolism genes, whereas those in the co-occurring microorganisms were mostly involved in genetic information storage and processing. Detection of Trichodesmium genes involved in P uptake and As detoxification suggest that local enrichment of N through N(2) fixation may lead to a P-stress response. Although containing similar dominant transcripts to open ocean metatranscriptomes, the overall pattern of gene expression in Trichodesmium colonies was distinct from free-living pelagic assemblages. The identifiable genes expressed by Trichodesmium and closely associated microorganisms reflect the constraints of life in well-lit and nutrient-poor waters, with biosynthetic investment in nutrient acquisition and cell maintenance, which is in contrast to gene transcription by soil and coastal seawater microbial assemblages. The results provide insight into aggregate microbial communities in contrast to planktonic free-living assemblages that are the focus of other studies.


[Laryngeal function preserving surgery in elderly hypopharygeal carcinoma].
To explore the indications and the effective treatment methods of laryngeal function preserva tion in aged patients with hypopharyngeal carcinoma. Clinical data about 41 patients with hypopharygeal carcinoma were analysed. These patients were more than or equal to 60 and were treated from January 2006 to December 2011. Among them, 25 cases were treated with laryngeal functions preserved and the hypopharynx defect was immediately re paired by the adjacent tissue flap or (and) the pactoralis major myocutaneous flap according to the size of defect after tumor resecting. The survival rate was calculated by Kaplan-Meier method. In 25 patients with laryngeal function preservation, 16 cases were 60-69 years old, 6 cases were 70-79 years old and 3 cases were 80-88 years old. The tumour located at lateral wall of pyriform sinus in 14 cases, at anterior wall of pyriform sinus in 3 cases, at inside wall of pyriform sinus in 3 cases, at upper side wall of hypopharynx invading tonsil or tongue base in 3 cases, at posterior hypopharyngeal wall in 2 cases. The average length of post-operation stay was 22.2 days. Eight cases suffered from post-operative complications (32%), including of pharyngeal fistula in six cases and pulmonary infection in two cases. The respiratory function and pronunciation were all restored, in 25 cases, among which 20 cases removed tracheostomy tube about 3 months after surgery. 2 cases were missed after 1-year followed up. 2 cases died of local tumor recurrence. 4 cases died of neck recurrence. 8 cases died of pulmonary matastasis. The 1-year and 3-year survival rate of the disease in the group was 67.5% and 43.9% respectively. As the aged cases of hypopharygeal carcinoma are choosed appropriately and repaired feasibly, surgery for the disease with laryngeal function retention may be safe and effective.


Regulation of intermediary metabolism by the PKCdelta signalosome in mitochondria.
PKCδ has emerged as a novel regulatory molecule of oxidative phosphorylation by targeting the pyruvate dehydrogenase complex (PDHC). We showed that activation of PKCδ leads to the dephosphorylation of pyruvate dehydrogenase kinase 2 (PDK2), thereby decreasing PDK2 activity and increasing PDH activity, accelerating oxygen consumption, and augmenting ATP synthesis. However, the molecular components that mediate PKCδ signaling in mitochondria have remained elusive so far. Here, we identify for the first time a functional complex, which includes cytochrome c as the upstream driver of PKCδ, and uses the adapter protein p66Shc as a platform with vitamin A (retinol) as a fourth partner. All four components are necessary for the activation of the PKCδ signal chain. Genetic ablation of any one of the three proteins, or retinol depletion, silences signaling. Furthermore, mutations that disrupt the interaction of cytochrome c with p66Shc, of p66Shc with PKCδ, or the deletion of the retinol-binding pocket on PKCδ, attenuate signaling. In cytochrome c-deficient cells, reintroduction of cytochrome c Fe(3+) protein restores PKCδ signaling. Taken together, these results indicate that oxidation of PKCδ is key to the activation of the pathway. The PKCδ/p66Shc/cytochrome c signalosome might have evolved to effect site-directed oxidation of zinc-finger structures of PKCδ, which harbor the activation centers and the vitamin A binding sites. Our findings define the molecular mechanisms underlying the signaling function of PKCδ in mitochondria.


[Arterial thrombolysis and angioplasty in atheromatous basilar artery occlusion].
Basilar occlusions treated with conventional therapy (anticoagulants or antiplatelets) have a poor outcome (80p. cent mortality). This unfavorable outcome may require a treatment within 6 hours by intra-arterial thrombolysis, sometimes followed by percutaneous transluminal angioplasty (PTA) in case of atherothrombotic occlusion due to a tight atherosclerotic stenosis. A 48 year-old patient, presented with left hemiparesis, left multimodal hypoesthesia, paralytic dysarthria. CT-scan showed a spontaneous hyperdensity of the basilar artery and arterial occclusion was confirmed by angiography, which showed an atherothrombotic occlusion involving the proximal part of the vessel. Intra-arterial thrombolysis began five hours after the onset with 0,25mg/kg of Rt-Pa (Actilyse((R))), given by bolus followed by 4 others bolus of 10mg. After a total dose of 60mg, arterial recanalization was obtained showing a tight atherosclerotic stenosis involving the proximal part of the basilar artery. PTA was performed 18 hours later with a ballon inflation at 6 atmospheres during 20 seconds. It allowed to decrease the stenosis from 80p. cent to 60p. cent. The patient recovered and MRI at D20 showed a small right lateral infarct involving the pons. Our study confirms the usefulness of intra-arterial thrombolysis in basilar artery occlusion. Consecutive PTA may be proposed in case of associated atherosclerotic stenosis, and the interest of PTA is further discussed.


[A study on the reflex arc outside the central nervous system with sympathetic ganglia as the centre].
The distribution of SP-like immunoreactivity in the sensory and sympathetic ganglia, as well as the fiber connection between sensory ganglia and sympathetic ganglia (SG) were studied by the immunohistochemical ABC and HRP methods. A large number of SP-like neurons were found in all dorsal root ganglia (DRG), and a large number of SP-like fibers and terminals were found in both thoracic SG and coeliac-cranial mesenteric ganglion complex (CCMG), but no SP positive perikaryons were seen in those ganglia. The various nerves connected with the CCMG have been cut, the results demonstrate that the SP immunoreactive material in the ganglion were only decreased obviously or disappeared by cutting the DRG associated with the CCMG. After injecting HRP into T7-9DRG, a few of labelled neurons were found in thoracic SG of the relative segments and CCMG. The results mentioned above revealed that SP-containing fibers and terminals present in the SG come from collateral branches of primary sensory neurons in the DRG, the postganglionic fibers from principal ganglion neurons in the SG projecting to the DRG, the connection of reciprocal fibers are present between the DRG and the SG. It is suggested that a reflex shortloop outside the central nervous system may be formed directly by primary afferent neuron and sympathetic postganglionic neuron for the purpose of regulating the activity of autonomic nervous system and, moreover the sympathetic nerve may have a feedback regulation function to the primary afferent. The results mentioned above offer the partial morphological testimony for the expoundity of acupuncture mechanism.


Optical changes of the human cornea as a function of age.
To assess the changes of the surfaces and optical properties of the cornea as a function of age. The corneal shape of 407 normal eyes of 211 subjects with ages ranging from 4 to 79 years old was determined by means of Scheimpflug imaging. These data were analyzed by fitting their elevation topographies to a general surface model, which consists of a biconic plus a Zernike polynomial expansion. The analysis includes the computation of the position and orientation of the model in the three-dimensional space to determine the orientation of the optical axis and the apex coordinates. Both average corneal surfaces show negative conic constant plus higher order aspheric terms Z(0)(4) and Z(0)(6) are significant). These surfaces are misaligned between them and with the line of sight. Such misalignment increases with age as the cornea seems to rotate as a solid body. The apex curvature and the magnitude of the conic constant along the most curved meridian increase as well, but the largest change with age correspond to the aspheric terms Z(0)(4) and Z(0)(6). As a result, the spherical aberration (SA) of the average cornea increases with age at a rate similar to the total SA of the eye. The average corneal surfaces are misaligned general aspheres. Corneal SA is higher than total SA, but both SAs increase with age at a similar rate. This confirms that the lens is partially compensating SA and that such compensation is preserved with aging. Misalignment and solid body rotation seem to reduce astigmatism and coma for young and middle-aged corneas.


Ileo-neorectal anastomosis: medium- and long-term follow-up of 37 patients.
Ileo-neorectal anastomosis (INRA), an alternative restorative procedure, was developed to reduce the pouch-related complication rate with an (at least) equal functional result. For this surgical outcome, data of all INRA patients, including bowel function and complications, were prospectively recorded. The reservoir capacity was determined repeatedly by physiologic tests. The anal sphincter complex was assessed by manometry and ultrasound examination. Evaluation of the neorectal mucosa was performed by endoscopy. An INRA procedure was carried out in 39/53 selected patients (47 ulcerative colitis and 6 familial adenomatous polyposis). Fourteen UC cases were converted to ileal pouch anal anastomosis or proctectomy only, because of impossibility to completely remove the rectal mucosa or short of length of the rectal stump. The median operation time for INRA was 323 min (range 240-518), with 1,400 ml blood loss (400-4,500). The reservoirs were permanently defunctioned in 2 patients--one because of reclassification into Crohn's disease, and one with pouchitis refractory to medical treatment. In 18 out of 37 cases, web-like stenoses occurred at the mucosa-anal level, which were treated by single (9) or repeated (5) dilatation or surgical stenoplasty (2). No pouch-related complications like pelvic sepsis, fistula or sexual dysfunction occurred. Thirteen patients had episodes of 'pouchitis', successfully treated with antibiotics, and 7 other cases, with functioning reservoirs, also had proximal 'non-specific' (i.e. no histological criteria of Crohn's disease found) small bowel inflammation. The median bowel frequency decreased from 15x/24 h initially to 7x/24 h at 2 years. Continence was perfect in 24/37 cases. Twelve out of 37 cases had occasional nocturnal soiling and passive nocturnal fecal incontinence was reported by 2/37 patients. The neorectal compliance volume recovered from 12.5 ml kPa after subtotal colectomy and 11 ml/kPa at 6 months after INRA to a neorectal compliance of 24 ml/kPa at 2 years' follow-up (p < 0.002; Wilcoxon signed rank test). The INRA procedure shows a low complication rate and reasonable functional results, there was however a considerable conversion rate in these first 53 cases and a high incidence of reclassification to CD.


Prognostic impact of immunoparesis at diagnosis and after treatment onset in patients with light-chain amyloidosis.
Immunoparesis (IP) is a risk factor associated with an unfavourable outcome in several plasma cell disorders. It has been suggested that its presence in light-chain (AL) amyloidosis could be associated with worse prognosis. However, the relevance of IP after treatment has not been evaluated to date. The aim of this study was to determine the prognostic impact of IP at diagnosis and one year after treatment onset in patients with AL amyloidosis. The clinical records of 69 patients with AL amyloidosis treated at a single institution from January 2006 to January 2016 were included in the study. IP was observed in 27.5% of patients at diagnosis. The presence of IP was associated with a lower probability to achieve very good partial response or better after first-line treatment (37.8% versus 62.2%; p = .04). However, only in the group of patients treated with autologous stem cell transplantation (ASCT), the presence of IP resulted in a shorter progression-free survival (PFS) (30.2 months versus not reached [NR]; p = .02) but not in overall survival (OS). Persistence of IP at one year after treatment onset was identified in only four (9.8%) of the 41 evaluable patients. In the ASCT group, the absence of IP at one year after treatment onset resulted in a longer median PFS and OS (NR versus 22.6 months; p = .006; and NR versus 35.2 months; p < .001; respectively). In the multivariate analysis, the absence of IP at one year after treatment onset was independently associated with longer survival. IP at diagnosis has a negative impact on survival while its absence at one year after treatment is an independent marker for long-term survival.


The effect of acute aerobic exercise on hemostasis in obstructive sleep apnea.
Individuals with obstructive sleep apnea (OSA) have an altered hemostatic balance; however, the exercise response is less described. The purpose of this study is to determine the hemostatic response after acute aerobic exercise in obstructive sleep apnea. Eighteen males (nine OSA vs. nine controls) were recruited from the university and local community. Individuals with evidence of cardiovascular, pulmonary, or metabolic disease were excluded. An apnea-hypopnea index (AHI) of >5 was a criterion for OSA. Subjects performed a treadmill exercise test at 35 and 70% predicted VO2 reserve during the morning hours. Pre-exercise blood samples were obtained after 15 min supine rest and within 2 min following exercise. Repeated measures ANOVA were performed for factor VIII antigen, tissue plasminogen activator (tPA) antigen, tPA activity, and PAI-1 activity. Correlational analysis compared resting and post-exercise hemostatic factors with age, BMI, and AHI. Mean AHI was 13.00 ± 12.6. No exercise × condition interactions were observed for hemostatic markers. There was a main effect for exercise in factor VIII, tPA antigen, and tPA activity in both groups. PAI-1 activity tended to be elevated in OSA (145%) compared to controls which remained after exercise (205%) (P = 0.05). Post-exercise FVIII/Ag correlated with BMI (r = 0.52), while resting tPA/Ag correlated with AHI (r = 0.49) and age (r = 0.50). The hemostatic response after acute aerobic exercise is unaffected in mild OSA, although PAI-1 activity seems to be elevated, reducing fibrinolytic potential. BMI seems to correlate with FVIII/Ag, while tPA/Ag is associated with AHI and age.


Cosmetic skin lightening use and side effects.
Cosmetic skin lightening is a growing dermatologic public health problem that affects communities of color worldwide. Despite well-documented adverse health effects, cosmetic skin lightening continues to be a popular practice among patients of color. Given the US's changing demographics, it is critical for dermatologists to be knowledgeable about the medical impact as well as social and cultural implications of this practice. This review article aims to serve as a primer for the dermatologist on the medical and sociocultural aspects of cosmetic skin lightening, as well as an approach to discuss the issue of cosmetic skin lightening with patients. We conducted a comprehensive PubMed search using the terms 'skin lightening agents,' 'skin bleaching,' and 'depigmenting agents,' and reviewed the literature on cosmetic skin lightening products, active ingredients, and adverse side effects. Herein, we review the prevalence, ingredients, and health implications of cosmetic skin lightening products. We also provide recommendations for counseling patients who practice cosmetic skin lightening in a culturally sensitive manner.


Eukaryotic translation elongation factor 1δ, N-terminal propeptide of type I collagen and cancer-associated fibroblasts are prognostic markers of oral squamous cell carcinoma patients.
Identifying markers that influence oral squamous cell carcinoma (OSCC) prognosis is a fundamental strategy to improve the overall survival of patients. Markers such as eukaryotic translation elongation factor 1δ (EEF1D), fascin, N-terminal propeptide of type I collagen (PINP), and cancer-associated fibroblasts (CAFs) have been noticed in OSCCs and their levels are closely related to the prognosis of tumors. Our aim was to confirm the role of those markers in OSCC prognosis. Immunohistochemistry was performed in 90 OSCC specimens. The associations between clinicopathologic features and expression of markers were assessed by χ2 test. Kaplan-Meier curves and univariate and multivariate Cox regression models were used for survival analysis. Markers were analyzed individually and in combination. High expression of EEF1D (P = .017) and PINP (P = .02) and abundant density of CAFs in tumor stroma (P = .005) predicted significantly poor survival in OSCC patients. Multivariate analysis revealed that all 3 parameters are individually independent prognostic factors of OSCC patients, and their combination improved the discrimination of patients at high risk for poor survival. Our results suggested that the expression of EEF1D and PINP and the density of CAFs might influence the survival of patients with OSCC.


Effective but uncommon treatment of a spontaneous otogenic epidural pneumocephalus.
We describe an uncommon treatment for epidural pneumocephalus and an effective but uncommon treatment option. Complete and permanent relief was achieved in a young patient using a tympanostomy tube to eliminate excessive positive air pressure in the mastoid bone that was the cause of spontaneous pneumocephalus. The patient showed no recurrence and absence of clinical symptoms at outpatient follow-up. Post-traumatic, infectious or spontaneous pneumocephalus may require an active, usually surgical approach. Treatment with a tympanostomy tube can be an alternative in suitable patients.


Secretion of inhibin A and follicular dynamics throughout the estrous cycle in the sheep with and without the Booroola gene (FecB).
The identification of a single gene (Booroola FecB) associated with a significant increase in the ovulation rate in sheep provides a powerful tool for the study of factors regulating the selection of preovulatory follicles. The ovarian secretion of dimeric inhibin A was investigated and related to the secretion of ovarian steroids, the concentration of gonadotropins, and the pattern of ovarian follicular development during the follicular and early luteal phases in ewes with an ovarian autotransplant with or without the FecB gene. The secretion of inhibin A was related to the presence of large estrogenic follicles, being high during the follicular phase and falling after the LH surge (P < 0.05) before increasing during the early luteal phase (P < 0.05). There were no differences in the timing of the onset of the LH surge, the concentrations of FSH and progesterone, or the rates of inhibin A, estradiol, and androstenedione secretion during the follicular or luteal phase between ewes with and without the Booroola gene. Although the overall pattern of follicular development was similar between the genotypes, the ovulation rate was higher (P < 0.05) in the gene carrier ewes, and the ovulatory follicles and corpora lutea were significantly smaller (P < 0.05) than those in noncarrier animals. During the luteal phase, the diameter of the large follicles from the first wave was smaller (P < 0.05) in the gene carrier than in noncarrier ewes. Because there are no qualitative or quantitative differences in the pattern of secretion of pituitary gonadotropins or ovarian hormones between the two genotypes, we conclude that is likely that the FecB gene exerts its action at the level of ovary.


Augmented adherence and internalization of group A Streptococcus pyogenes to influenza A virus infected MDCK cells.
Respiratory tract infections are one of the leading causes of morbidity and mortality. There is considerable epidemiologic evidence that infection with respiratory viruses increases the incidence and severity of secondary bacterial complications. However, very limited number of studies were concerned with the mechanism behind such synergy. In this context, our study aimed to explore the interaction between Group A Streptococcus pyogenes (GAS) and Influenza A virus (IAV). Our results revealed that the GAS adherence and internalization into Madin-Darby canine kidney (MDCK) cells markedly increased after IAV infection. When M6 protein defective mutant of GAS was used, the virus enhanced adherence and internalization was nearly abolished indicating the involvement of M protein binding sites on the MDCK cell surface. Interestingly, the modulation of some O-linked glycolproteins as well as sialic acid, mucin and fibrinogen-like residues on the surface of MDCK cells contributed to augmented bacterial adherence and/or internalization. In the same way, qRT-PCR experiments showed an overexpression of the membrane associated mucin (MUC1) on the surface of the MDCK cells after IAV infection. Altogether, the present study revealed that IAV infection augments the adherence and internalization of GAS to MDCK cells via modulation of membrane associated O-linked glycoproteins, fibrinogen, sialic acid residues and the mucin, MUC1 on the surface of MDCK cell.


Regulation of glucuronidation by glutathione redox state through the alteration of UDP-glucose supply originating from glycogen metabolism.
The effect of altered redox state of glutathione was investigated on p-nitrophenol glucuronidation in isolated mouse hepatocytes. Decrease of GSH/GSSG ratio provoked by various agents caused increased glucuronidation which was accompanied by stimulated glycogenolysis and elevated UDP-glucose content. The stimulation of glycogenolysis and glucuronidation by glutathione consumption could be prevented by the reduction of oxidized glutathione with dithiothreitol and by the glycogenolysis inhibitor fructose. In permeabilized hepatocytes glycogen metabolism, bypassed by the addition of UDP-glucose, stimulated glucuronidation which was insensitive to glutathione depletion. In liver microsomes either UDP-glucuronosyltransferase activity or UDP-glucuronic acid transport was not influenced by GSH/GSSG ratio. These results suggest that alteration of the GSH/GSSG ratio regulates glucuronidation by affecting enzymes of the glycogen metabolism via the modification of UDP-glucuronate supply.


fosA3 overexpression with transporter mutations mediates high-level of fosfomycin resistance and silence of fosA3 in fosfomycin-susceptible Klebsiella pneumoniae producing carbapenemase clinical isolates.
The effective treatment of carbapenemase-producing Klebsiella pneumoniae infection has been limited and required novel potential agents. Due to the novel drug development crisis, using old antimicrobial agents and combination therapy have been highlighted. This study focused on fosfomycin which inhibits cell wall synthesis and has potential activity on Enterobacteriaceae. We evaluated fosfomycin activity against carbapenemase-producing K. pneumoniae and characterized fosfomycin resistance mechanisms. Fosfomycin revealed effective activity against only 31.8% of carbapenemase-producing K. pneumoniae isolates. The major resistance mechanism was FosA3 production. The co-occurrence of FosA3 overexpression with the mutation of glpT (or loss of glpT) and/or uhpT was mediated high-level resistance (MIC>256 mg/L) to fosfomycin. Moreover, fosA3 silenced in sixteen fosfomycin-susceptible isolates and the plasmid carrying fosA3 of these isolates increased 32- to 64-fold of fosfomycin MICs in Escherichia coli DH5α transformants. The in vitro activity of fosfomycin combination with amikacin by checkerboard assay showed synergism and no interaction in six (16.2%) and sixteen isolates (43.3%), respectively. No antagonism of fosfomycin and amikacin was observed. Notably, the silence of aac (6)'-Ib and aphA6 was observed in amikacin-susceptible isolates. Our study suggests that the combination of fosfomycin and amikacin may be insufficient for the treatment of carbapenemase-producing K. pneumoniae isolates.


Comparison of patients satisfaction levels in public and private tertiary care centres.
The purpose of our study was to compare patient satisfaction level among tertiary public and private hospitals. We carried out a multi-centre cross-sectional study using Patient SatisfactionQuestionnaire-18 to assess patient satisfaction in a major private and public hospital in Islamabad. Out of 1301 participants, 636 (48.9%) patients were at the public hospital, while 665(51.1%) were at the private hospital. Time spent with doctor, communication, accessibility and convenience component score was significantly higher in patients at the private hospital (p<0.05 each). Interpersonal manner component score was higher at the public hospital (p<0.05). Female patients, patients admitted in medical specialty and patients admitted in private hospitals had higher patient satisfaction score<lt;0.05 each). Significant efforts should be made to improve the quality of care provided to patients admitted in public-sector health facilities.


A role for single-stranded templates in cell-free adeno-associated virus DNA replication.
Assays have been described in which duplex adeno-associated virus (AAV) DNA can be replicated in HeLa cell extracts with exogenous AAV Rep protein. These assays appear to mimic the AAV DNA replication that occurs in the cell, including the ability of extracts from adenovirus (Ad)-infected cells to replicate duplex AAV DNA templates more efficiently than extracts from uninfected cells can. We showed previously that the Ad-infected extract was able to support a more processive replication than the uninfected extract. When the Ad single-stranded DNA binding protein (Ad-DBP) was added to an uninfected extract, DNA replication became processive. Based on a strand displacement replication model, we hypothesized that the Ad-DBP was stabilizing the displaced single-stranded DNA during strand displacement replication. In this report, we show that in Ad-infected extracts most of the newly replicated duplex DNA is converted into a single-stranded form shortly after synthesis. Using the results of assays for the replication of single-stranded AAV DNA, we show that these single-stranded molecules serve as templates for additional replication. In addition, we identify a class of molecules which are likely to be intermediates of replication on single-stranded templates. We discuss a possible role for replication of single-stranded molecules in the infected cell.


The combined evaluation of p53 accumulation and of Ki-67 (MIB1) labelling index provides independent information on overall survival of ovarian carcinoma patients.
The prognostic implications of p53 accumulation, bcl-2 immunoreactivity and tumour proliferative fraction in ovarian carcinomas are still debated. One hundred twelve ovarian carcinomas were immunostained for p53 protein, for bcl-2 and for the cell cycle-associated Ki-67 antigen. The immunostaining results were correlated with conventional clinico-pathological variables, response to induction chemotherapy, and patient survival. p53 accumulation and bcl-2 immunoreactivity in more than 10% of neoplastic cells were detected in 61 (54.5%) and 42 (37.5%) cases, respectively. A positive correlation between p53 accumulation and high (more than 30% neoplastic cells) MIB1 labelling index (r = 0.235; P = 0.015) was ascertained, whereas no significant association was found between bcl-2 immunoreactivity and p53 accumulation or MIB1 labeling index. Both p53 accumulation and MIB1 immunoreactivity correlated significantly with a reduced overall survival, but the association was lost in multivariate analysis. However, patients with tumours simultaneously showing p53 accumulation and MIB1 labelling index higher than 30% had significantly reduced overall survivals, in both univariate and multivariate analyses. The simultaneous evaluation of p53 accumulation and MIB1 labelling index has independent prognostic implications in common epithelial malignancies of the ovary, irrespective of the disease stage.


Chlorophyll-Protein Complexes from Euglena gracilis and Mutants Deficient in Chlorophyll b: II. Polypeptide Composition.
Chlorophyll-protein complexes (CPs) obtained from thylakoids of Euglena gracilis Klebs var bacillaris Cori contain the following polypeptides (listed in parentheses in order of prominence after Coomassie R-250 staining of polyacrylamide gels): CP Ia (66, 18, 22, 22.5, 27.5, 21, 28, 24, 25.5, and 26 kilodaltons [kD]); CP I (66 kD); CPx (41 kD); LHCP(2) (an oligomer of LHCP) (26.5, 28, and 26 kD); CPy (27 and 19 kD); CPa (54 kD); and LHCP (26.5, 28, and 26 kD). Mutants of bacillaris low in chlorophyll b (Gr(1)BSL, G(1)BU, and O(4)BSL; Chl a/b [mol/mol] = 50-100) which lack CP Ia, LHCP(2), and LHCP also lack or are deficient in polypeptides associated with these complexes in wild-type cells. Mutants G(1) and O(4), which also lack CPy, lack the CPy-associated polypeptides found in wild-type and Gr(1). Using an antiserum which was elicited by and reacts strongly and selectively with the SDS-treated major polypeptide (26.5 kD) of the LHCP complexes of wild-type, this polypeptide is undetectable in the mutants (<<0.25% of the level in wild-type on a cell basis); the antiserum does not react with the SDS-treated 28 kD polypeptide of the Euglena LHCP complexes and cross-reacts only very weakly with components in SDS-treated cells of Chlamydomonas reinhardtii Dangeard and chloroplasts of Spinacia oleracea L. cv Winter Bloomsdale. Rates of photosynthesis of the wild-type and mutant cells of Euglena are approximately equal on a cell basis when measured at light saturation, consistent with the selective loss of major antenna components but not CP I or CPa from the mutants.


Is endometrial development in the peri-implantation period influenced by high concentrations of luteinizing hormone in the follicular phase?
A retrospective study was designed to examine the relationship between luteinizing hormone (LH) concentrations in the follicular phase and endometrial development in the luteal phase of natural and artificial cycles. Two types of cycle were studied: natural cycles (n = 51) in subjects with unexplained infertility were divided into two subgroups, depending on whether LH measurements in the late follicular phase were based on urine (n = 24) or plasma (n = 27) samples; and artificial cycles (n = 17), produced by the administration of a standard hormone replacement therapy, in two subgroups of women, those with premature ovarian failure (n = 10) in whom plasma LH concentrations were high, and those with unexplained infertility (n = 7) who had their hypothalamic pituitary-ovarian axis down-regulated and in whom plasma LH concentrations were low. The correlation between plasma or urine concentrations of LH in the follicular phase and the results of endometrial biopsy obtained in the luteal phase was calculated. In natural cycles, LH concentrations were similar in those with normal or retarded endometrium, and there was no significant correlation between high LH concentration and retarded endometrial development. In artificial cycles, endometrial development was not different between those with low LH concentrations (down-regulated by Zoladex) and those with high LH concentrations (premature ovarian failure). Endometrial development in the peri-implantation period does not appear to be influenced by LH concentration in the follicular phase. The reported association between high LH concentration and poor reproductive performance cannot therefore be explained by abnormal implantation consequent upon retarded endometrial development.


Medicine and the media: Medical experts' problems and solutions while working with journalists.
Medical experts are one of the main sources used by journalists in reporting on medical science. This study aims to 1) identify problems that medical experts encounter in contacts with the media representatives, 2) elucidate their attitudes about interactions with journalists and 3) reflect on solutions that could improve the quality of medical journalism. By using in-depth interviews, focus groups and a survey directed to 600 medical experts in 21 countries, this cohort study elucidates medical experts' experiences and views on participating in popular media. A strong interest in interacting with the media was identified among the experts, where nearly one fifth of the respondents in the survey claimed that they contacted the media more than 10 times per year. Six obstacles for improving the quality of medical reporting in the media were found: deadlines, headlines, choice of topic or angle, journalist's level of medical knowledge, differences in professional culture and colleagues' opinions. The main concern among experts was that short deadlines and exaggerated headlines could harm journalistic quality. It is possible that this is partly due to ongoing changes in the media landscape with many new platforms and less control functions. Nevertheless, for several reasons many experts have great interest in interacting with the media, something that could contribute to better communication and fewer misunderstandings. Our results highlight factors like expert networks, media training for scientists and regular meetings that may facilitate communication between medical experts and medical reporters.


[Efficacy and safety of recombinant human growth hormone solution in children with growth hormone deficiency in China: a multicenter trial].
Human growth hormone (hGH) is an essential therapeutic drug for the treatment of growth hormone (GH) deficiency (GHD). However, the process of dissolving hGH of the powder form is complicated and potentially hazardous. In the present study, we evaluated the efficacy and safety of preparation in the replacement therapy for children with GH deficiency. A 12-month randomized, open-label, multicenter trial was conducted in 31 previously untreated children with growth failure secondary to GH deficiency [20 boys and 11 girls, mean age (10.5 +/- 4.1) years]. An recombined human growth hormone (rhGH) solution (Iintropin AQ) was given via subcutaneous injection daily in every evening at a weekly dose of 0.25 mg/kg. The patients were followed up at 3, 6, 9, and 12 months of the treatment, and the course of treatment was 12 months. Body height was measured 3-monthly and height velocity (HV) and mean height standard deviation score (HT SDS) were calculated. Serum Insulin-like growth factor I (IGF-1), Insulin-like growth factor binding protein 3 (IGFBP-3), GH antibodies and safety parameters were assessed at the baseline and at 3-month intervals. Bone age (BA) was assessed at the baseline and the rate of skeletal maturation (DeltaBA/DeltaCA) was calculated after 6 and 12 months of rhGH treatment by a central bone age reader. Moreover, the safety of rhGH solution treatment was assessed. After 12 months of liquid rhGH therapy, growth parameters were significantly increased over baseline. (1) The mean (+/- SD) height increment DeltaHT (cm) was 4.0 +/- 1.3, 7.0 +/- 2.0, 10.3 +/- 2.6 and 12.9 +/- 3.3 after 3, 6, 9, and 12 months of treatment, respectively (P < 0.01), which indicated linear growth after treatment. The GV (cm/years) was 2.7 +/- 0.9 before treatment and increased to 16.0 +/- 5.1, 14.1 +/- 4.0, 13.7 +/- 3.5, and 12.9 +/- 3.3 after treatment, suggesting that catch-up growth was significant after treatment as compared to the pre-treatment status (P < 0.01). Accordingly, post-treatment catch-up growth was obvious, significant differences were observed in HT SDS, which was -4.62 +/- 1.46 at the onset of therapy and increased significantly after the treatment to -3.80 +/- 1.53, -3.28 +/- 1.60, -2.86 +/- 1.75 and -2.47 +/- 1.86, respectively (P < 0.01). The height difference between GH deficient children and unimpaired children of the same age and gender gradually decreased after treatment, which was significantly different from that seen before treatment (P < 0.01). (2) The levels of serum IGF-1 and IGFBP-3 were increased comparably for the treatment. IGF-1 level (microg/L) was 41 +/- 64 at baseline and increased to 179 +/- 155, 202 +/- 141, 156 +/- 155 and 159 +/- 167 after 3, 6, 9, 12 months of treatment. IGFBP-3 level (mg/L) was 1540 +/- 1325 at baseline, and increased to 3891 +/- 1815, 4051 +/- 1308, 3408 +/- 1435 and 3533 +/- 1413, respectively, suggesting that with the increases in height, IGF-1, and IGFBP-3 were significantly activated to relatively high levels by the medication and reached peak values between 3 and 6 months of treatment. The levels of IGF-1 and IGFBP-3 were significantly different before and after treatment (P < 0.01). The IGF-1/IGFBP-3 molar ratio significantly increased during GH therapy (0.143 +/- 0.013 pre-therapy up to 0.240 +/- 0.055 post-therapy, P < 0.01). The IGF-1/IGFBP-3 molar ratio tended to stabilize after 3-month GH therapy. (3) The bone age assessment carried out 6 and 12 months after treatment showed that the bone maturity (DeltaBA/DeltaCA) was 1.01 +/- 0.57 and 1.07 +/- 0.75, respectively, suggesting that there was no speed-up development in the bone age. No severe adverse events were observed during the trial and the most frequent accompanying event was mild hypothyroidism. rhGH solution (Iintropin AQ) is a safe and effective preparation in the replacement therapy for children with GH deficiency.


Secondary Kwashiorkor Disease in a Patient with Gastric Bypass Surgery and Short Gut Syndrome.
BACKGROUND Kwashiorkor disease is a subtype of severe acute protein malnutrition characterized by peripheral edema associated with hypoalbuminemia and ascites. It can result from both protein deficiency and protein loss. In resource-poor countries, the disease often is caused by inadequate dietary intake, but in resource-rich countries, it can be seen as a rare complication of severe malabsorption. CASE REPORT We present the case of a 60-year-old woman who presented with 1 week of progressive anasarca in the setting of decreased dietary intake and poor tolerance of total parenteral nutrition (TPN). She had a history of Roux-en-Y gastric bypass surgery which was complicated by a strangulated internal hernia that required an exploratory laparotomy and small bowel resection. She subsequently developed short gut syndrome with TPN dependence. Work-up revealed hypoalbuminemia with several micronutrient deficiencies consistent with secondary kwashiorkor disease. With a multidisciplinary approach that included Gastroenterology, Pharmacy, and Nutrition, she was treated with albumin, furosemide, nutritional supplementation, and ultimately rechallenged with TPN. At discharge, her swelling had improved, her weight had decreased, and her albumin improved to the normal range. CONCLUSIONS This case is a unique presentation of secondary kwashiorkor disease. In our patient, the combination of gastric bypass surgery and short gut syndrome with poor TPN tolerance likely led to severe protein malabsorption. This underscores the importance of recognizing the signs and symptoms of kwashiorkor disease and understanding the associated complications so that treatment can be instituted promptly. Furthermore, the case demonstrates how an interdisciplinary approach to management can increase the chance of a successful outcome.


Activated Carbon from Palm Date Seeds for CO2 Capture.
The process of carbon dioxide capture and storage is seen as a critical strategy to mitigate the so-called greenhouse effect and the planetary climate changes associated with it. In this study, we investigated the CO2 adsorption capacity of various microporous carbon materials originating from palm date seeds (PDS) using green chemistry synthesis. The PDS was used as a precursor for the hydrochar and activated carbon (AC). Typically, by using the hydrothermal carbonization (HTC) process, we obtained a powder that was then subjected to an activation step using KOH, H3PO4 or CO2, thereby producing the activated HTC-PDS samples. Beyond their morphological and textural characteristics, we investigated the chemical composition and lattice ordering. Most PDS-derived powders have a high surface area (>1000 m2 g-1) and large micropore volume (>0.5 cm3 g-1). However, the defining characteristic for the maximal CO2 uptake (5.44 mmol g-1, by one of the alkaline activated samples) was the lattice restructuring that occurred. This work highlights the need to conduct structural and elemental analysis of carbon powders used as gas adsorbents and activated with chemicals that can produce graphite intercalation compounds.


Nucleon Spin and Momentum Decomposition Using Lattice QCD Simulations.
We determine within lattice QCD the nucleon spin carried by valence and sea quarks and gluons. The calculation is performed using an ensemble of gauge configurations with two degenerate light quarks with mass fixed to approximately reproduce the physical pion mass. We find that the total angular momentum carried by the quarks in the nucleon is J_{u+d+s}=0.408(61)_{stat}(48)_{syst} and the gluon contribution is J_{g}=0.133(11)_{stat}(14)_{syst}, giving a total of J_{N}=0.54(6)_{stat}(5)_{syst} that is consistent with the spin sum. For the quark intrinsic spin contribution, we obtain 1/2ΔΣ_{u+d+s}=0.201(17)_{stat}(5)_{syst}. All quantities are given in the modified minimal subtraction scheme at 2 GeV. The quark and gluon momentum fractions are also computed and add up to ⟨x⟩_{u+d+s}+⟨x⟩_{g}=0.804(121)_{stat}(95)_{syst}+0.267(12)_{stat}(10)_{syst}=1.07(12)_{stat}(10)_{syst}, thus satisfying the momentum sum.


Candida meningitis post Gliadel wafer placement successfully treated with intrathecal and intravenous amphotericin B.
To report a case of Candida meningitis post Gliadel wafer (polifeprosan 20 with carmustine implant) placement successfully treated with the combination of intrathecal and intravenous amphotericin B. A 33-year-old white female with a history of recurrent oligodendroglioma was admitted to the neuroscience intensive care unit with acute mental status changes. Computed tomography of the head demonstrated a cystic dilation of the right frontoparietal tumor resection cavity with Gliadel wafers in place and the presence of a large fluid collection. The cavity was debrided surgically and a ventriculostomy catheter was left in place. Cerebrospinal fluid (CSF) cultures were positive for Candida albicans and methicillin-resistant coagulase-negative Staphylococcus spp. Antiinfective therapy with intrathecal and intravenous amphotericin B as well as flucytosine and vancomycin was started. The patient had subsequent improvement in clinical manifestations, resolution of CSF leukocytosis, and mycologic cure. Candida meningitis occurs primarily in the setting of immunosuppression, intravenous drug abuse and following neurosurgical procedures. Secondary bacterial and fungal infections have been reported following Gliadel wafer placement in patients with brain tumor resection. Candida meningitis has traditionally been treated with intravenous amphotericin B with or without oral flucytosine. There have been reports of treatment with intrathecal amphotericin B with variable clinical outcomes. This case demonstrates successful treatment of Candida meningitis post Gliadel wafer placement with the combination of intrathecal and intravenous amphotericin B. This treatment modality may provide an effective therapeutic option for other patients with Candida meningitis, especially those unresponsive to intravenous therapy.


The pericardium reinforced suture annuloplasty: another tool available for mitral annulus repair?
From May 1985 to May 1992, 169 patients underwent surgery for mitral valve repair. In 87% of these patients, the valve reconstruction involved the mitral annulus. At the beginning, in an effort to preserve systolic movement of the annulus and avoid the implant of prosthetic materials inside the heart, we mainly used simple suture annuloplasty in 66 patients. When we reoperated upon three patients only a few months after reconstruction of the mitral valve for a dehiscence of the suture annuloplasty, we decided to perform ring annuloplasty with the Carpentier ring in 23 patients. Though we have not seen any problems with the Carpentier ring in our series, we performed a suture annuloplasty reinforced with a strip of autologous pericardium to eliminate all prosthetic material. Since introducing this technique in 1989, we have used this annuloplasty in 58 patients. We have not observed any dehiscence of the suture or other complications related to this procedure. Three patients with a pericardial annuloplasty underwent reoperation for other reasons; the autologous pericardium was perfectly attached to the annulus, covered by a smooth layer of fibrous tissue without calcification. After this encouraging initial experience, we believe that long-term follow-up is necessary to confirm that autologous pericardium is an effective method of mitral annulus repair.


Activating nuclear xenobiotic receptors and triggering ER stress and hepatic cytochromes P450 systems in quails (Coturnix C. coturnix) during atrazine exposure.
Atrazine (ATR) is one of the most widely detected contaminant in the ecosystem. Nuclear xenobiotic receptors are activated by herbicides and induce the transcription of CYP450 isoforms involved in xenobiotic metabolism and transport. However, little is known about hepatic nuclear xenobiotic receptors in birds are responsible for ATR-induced hepatotoxicity via regulating the cytochrome P450 enzyme systems (CYP450s). The objective of this study was to investigate the mechanism of ATR hepatotoxicity in quails. For this purpose, male quails were dosed by oral gavage from sexual immaturity to maturity with 0, 50, 250, and 500 mg/kg/day ATR for 45 days. The results showed that ATR exposure caused the hepatotoxicity damage and endoplasmic reticulum (ER) degeneration. It suggested that ER is a target organelle of ATR toxicity in hepatocytes. ATR exposure disrupted the hepatic CYP450s homeostasis. This study also demonstrated that ATR triggered the CYP450 isoforms transcription via activating the hepatic CAR/PXR pathway. The present study provides new insights regarding the mechanism of the ATR-induced hepatotoxicity through activating nuclear xenobiotic receptors and triggering ER stress and hepatic CYP450s in quails.


Effect of warfarin discontinuation on the incidence of postoperative bleeding in tooth extraction.
The number of patients undergoing oral anticoagulant therapy for cardiovascular and cerebrovascular disease is increasing. However, the risk of bleeding after tooth extraction in patients receiving warfarin is unclear. Here, we assess the risk of bleeding after tooth extraction in patients on warfarin. The study included 260 patients taking warfarin who underwent tooth extraction (694 teeth). The patients were divided into those whose teeth were extracted while they were taking warfarin, those who discontinued warfarin before extraction, and those who underwent extraction while receiving heparin bridging therapy. Bleeding complications in the two groups were compared. Of the 260 patients, 156 underwent extraction while taking warfarin, 70 stopped taking warfarin before extractions, and 34 received heparin bridging therapy and stopped taking either medication before extractions. Bleeding complications occurred in 9 patients (3.5%) and 9 tooth sites (1.3%). Among the 9 patients with bleeding complications, 6 underwent extraction while taking warfarin, 2 stopped warfarin before extraction, and 1 underwent extraction after receiving heparin bridging therapy. No significant difference was seen between patient groups regarding bleeding after extractions (P=0.917). Warfarin use does not increase the risk of post-extraction bleeding and can therefore be continued during tooth extraction.


The pursuit of immortality: from the ego to the soul.
Moderated by Lisa Miller from Newsweek, evolutionary biologist Kenneth Miller (Brown University) and theologians John Haught (Georgetown University) and Nancey Murphy (Fuller Theological Seminary) discuss the questions Are we immortal? Do our souls exist beyond our bodies? and What scientific evidence is there for mystical experience? from a cultural, historical, and scientific perspective. The following is an edited transcript of the discussion that occurred March 23, 2011, 7:00-8:15 PM, at the New York Academy of Sciences in New York City.


Benchmark Investigation of Band-Gap Tunability of Monolayer Semiconductors under Hydrostatic Pressure with Focus-On Antimony.
In this paper, the band-gap tunability of three monolayer semiconductors under hydrostatic pressure was intensively investigated based on first-principle simulations with a focus on monolayer antimony (Sb) as a semiconductor nanomaterial. As the benchmark study, monolayer black phosphorus (BP) and monolayer molybdenum disulfide (MoS2) were also investigated for comparison. Our calculations showed that the band-gap tunability of the monolayer Sb was much more sensitive to hydrostatic pressure than that of the monolayer BP and MoS2. Furthermore, the monolayer Sb was predicted to change from an indirect band-gap semiconductor to a conductor and to transform into a double-layer nanostructure above a critical pressure value ranging from 3 to 5 GPa. This finding opens an opportunity for nanoelectronic, flexible electronics and optoelectronic devices as well as sensors with the capabilities of deep band-gap tunability and semiconductor-to-metal transition by applying mechanical pressure.


Evodiamine induces reactive oxygen species-dependent apoptosis and necroptosis in human melanoma A-375 cells.
Melanoma is a common solid malignant tumor with a high frequency of metastasis and relapse. Evodiamine (EVO), a natural small molecule, has recently attracted considerable attention due to its pharmacological action, including its anticancer effects. However, the mechanism of the cytotoxic effect exerted by EVO on tumor cells is not yet fully understood. The present study aimed to evaluate the antitumor effects of evodiamine in human melanoma A-375 cells. The results demonstrated that EVO inhibited cell proliferation and induced cell cycle arrest at the G2/M stage in human melanoma A-375 cells. The results also revealed that EVO exposure induced the activation of caspase-3, caspase-9 and poly (ADP-ribose) polymerase 1, as well as mitochondrial membrane potential dissipation in a time-dependent manner, indicating that EVO induced intrinsic apoptosis in A-375 cells. Furthermore, the results revealed that receptor-interacting serine/threonine kinase (RIP) and RIP3 were sequentially activated, suggesting that necroptosis may also be involved in EVO-induced cell death in A-375 cells. In addition, co-treatment with catalase was demonstrated to significantly attenuate the EVO-induced cell death in A-375 cells, indicating that reactive oxygen species (ROS) may serve an important role in EVO-induced cell death. In conclusion, the results of the present study unveiled a novel mechanism of drug action by EVO in human melanoma cells and suggested its potential value in treating human melanoma by inducing cell death via ROS activation.