Differential in vivo tumorigenicity of distinct subpopulations from a luminal-like breast cancer xenograft.
Intratumor heterogeneity caused by genetic, phenotypic or functional differences between cancer cell subpopulations is a considerable clinical challenge. Understanding subpopulation dynamics is therefore central for both optimization of existing therapy and for development of new treatment. The aim of this study was to isolate subpopulations from a primary tumor and by comparing molecular characteristics of these subpopulations, find explanations to their differing tumorigenicity. Cell subpopulations from two patient derived in vivo models of primary breast cancer, ER+ and ER-, were identified. EpCAM+ cells from the ER+ model gave rise to tumors independently of stroma cell support. The tumorigenic fraction was further divided based on SSEA-4 and CD24 expression. Both markers were expressed in ER+ breast cancer biopsies. FAC-sorted cells based on EpCAM, SSEA-4 and CD24 expression were subsequently tested for differences in functionality by in vivo tumorigenicity assay. Three out of four subpopulations of cells were tumorigenic and showed variable ability to recapitulate the marker expression of the original tumor. Whole genome expression analysis of the sorted populations disclosed high similarity in the transcriptional profiles between the tumorigenic populations. Comparing the non-tumorigenic vs the tumorigenic populations, 44 transcripts were, however, significantly differentially expressed. A subset of these, 26 identified and named genes, highly expressed in the non-tumorigenic population, predicted longer overall survival (N = 737, p<0.0001) and distant metastasis free survival (DMFS) (N = 1379, p<0.0001) when performing Kaplan-Meier survival analysis using the GOBO online database. The 26 gene set correlated with longer DMFS in multiple breast cancer subgroups. Copy number profiling revealed no aberrations that could explain the observed differences in tumorigenicity. This study emphasizes the functional variability among cell populations that are otherwise genomically similar, and that the risk of breast cancer recurrence can only be eliminated if the tumorigenic abilities in multiple cancer cell subpopulations are inhibited.


[Early outcome of using Zero-profile implant system in treatment of cervical spondylosis].
To evaluate the early outcome of anterior cervical discectomy and fusion (ACDF) using a Zero-profile implant system (Zero-P) for interbody fusion in the treatment of cervical spondylosis. Between March 2010 and June 2011, 25 patients with cervical spondylosis underwent ACDF with Zero-P. There were 13 males and 12 females with an average age of 44.2 years (range, 26-67 years), including 14 cases of nerve root cervical spondylosis, 6 cases of spinal cervical spondylosis, and 5 cases of mixed cervical spondylosis. The disease duration was 3-120 months (median, 25 months). Single segment was involved in 20 cases, 2 segments in 4 cases, and 3 segments in 1 case. A total of 31 Zero-P were implanted (3 at C3, 4, 8 at C4, 5, 12 at C5, 6, and 8 at C6, 7). Primary cervical operation was performed in 23 cases and re-operation in 2 cases. Before and after operation, the height of intervertebral space and the cervical Cobb angle were measured; clinical outcome was evaluated using visual analogue scale (VAS) score for pain in the neck and upper limb, and Japanese Orthopaedic Association (JOA) score for myelopathy; and intervertebral fusion and the incidence of dysphagia were also observed. All incisions healed by first intention. All the patients were followed up 12-16 months (mean, 13.9 months). Interbody bone fusion was obtained, and the fusion time was 2.7-6.0 months (mean, 3.8 months). Three patients had dysphagia after operation; symptom disappeared at 1 week and 3 months after operation in 2 cases and 1 case, respectively. No fixation loosening, subsidence, or breakage occurred. The height of intervertebral space was significantly improved (P < 0.05) from (4.5 +/- 0.5) mm at preoperation to (6.0 +/- 0.7) mm at 1 week and (5.7 +/- 0.6) mm at 12 months after operation; the cervical Cobb angle was significantly improved (P < 0.05) from (11.9 +/- 6.1) degrees at preoperation to (21.2 +/- 4.1) degrees at 1 week and (20.2 +/- 3.7) degrees at 12 months after operation; and there was no significant difference between at 1 week and 12 months after operation (P > 0.05). The VAS score was significantly reduced (P < 0.05) from 7.1 +/- 0.8 at preoperation to 1.9 +/- 0.8 at 3 months and 1.0 +/- 0.5 at 12 months after operation; the JOA score was significantly increased (P < 0.05) from 9.6 +/- 1.3 at preoperation to 13.5 +/- 1.0 at 3 months and 14.9 +/- 1.0 at 12 months after operation; and there was significant difference between at 3 months and at 12 months after operation (P < 0.05). The early outcome of ACDF using a Zero-P in the treatment of cervical spondylosis is satisfactory and reliable, and it can restore and maintain the cervical alignment and disc height, and disc has low incidence of postoperative dysphagia.


Engaging racial autoethnography as a teaching tool for womanist inquiry.
Racial autobiography, self-narratives on how one learned about the idea of race, has been underutilized as a tool to familiarize and orient students in the process of critical inquiry for nursing research. The aims of this article are to explore how racial autoethnography: (1) repositions students to effect an epistemological change, (2) challenges dominant ideology, and (3) functions as a link between the student and critical theories for use in nursing research. Students engage in and share reflective narrative about a variety of instructional materials used in the course. Reflective narratives are presented in a framework that addresses white racial identity development.


Impact of a Pharmacist-Led Diabetes Care Service for Hispanic Patients at a Free Medical Clinic.
This article describes a pharmacist-led diabetes care program implemented at a local free clinic for underserved Hispanic patients with low or no income. Patients are referred to the pharmacist after diagnosis with diabetes for a consultation that includes disease state education, diet/lifestyle education, medication management, and follow-up. The pharmacist works with patients to ensure timely follow-up and adequate medication adjustments to achieve goals. In its first 16 months, this service led to a statistically significant decrease in A1C for Hispanic patients, with an average 2 percentage point reduction in A1C.


Management outcome of closed femoral shaft fractures by open Surgical Implant Generation Network (SIGN) interlocking nails.
Many hospitals in our country lack surgical expertise and operating room facilities like image intensifier and fractures table to carry out closed interlocking nails (ILN) in femoral shaft fractures. But availability of Surgical Implant Generation Network (SIGN) interlocking nails & nailing instrumentation have made open ILN of these fractures possible at very basic level of our health care system. We have carried out open SIGN nailing in patients with closed fractures of shaft femur without the use of image intensifier. Result for fracture union was evaluated both clinically and radio-logically, and graded at 8 months (32 weeks) after treatment by Thoressen's criteria. An experimental study of open SIGN nailing was carried out on 47 patients with fractures shaft of femur who had been admitted to our tertiary care hospital from January 2006 to December 2007. Inclusion criteria were adult patients older than 16 years with closed fractures of the shaft femur, and have presented within a week of the injury, and have not had any previous surgical treatment for the fracture. Malnourished patients and patients with open, pathological fractures and non union cases were excluded from the study. A standard protocol was followed on all patients, which is describing below. The data obtained was analysed using SPSS. The union rate was 97.83% in open nailing at 32 weeks after surgery and the Mean +/- SD time to union was 19.65 +/- 5.19 weeks (ranges from 16-32 weeks).We obtained excellent results in 39 patients (83.33%), good in 4 patients (8.50%), fair in 3 patients (6.38%) and poor in one (2.12%). The open SIGN nailing, without the use of image intensifier, for treatment of closed fractures of shaft femur achieves excellent result in term of fracture union. Results obtained are comparable to the results of closed interlocking nailing, requires less expertise and resources, and its use is recommended for long bones fracture care at the very level of our health care system.


De novo 15.5-Mb Interstitial Deletion in 5p in a Male Ascertained by Oligospermia.
We describe a case of a 34-year-old male presenting with oligospermia and an otherwise normal phenotype. Investigation with array-based comparative genomic hybridization (aCGH) revealed an interstitial deletion of about 15.5 Mb in chromosome 5p13.3p14.3. We compared the phenotype of our patient with recently reported patients studied by aCGH, who show an overlapping deletion. We also analyzed the gene content of the deleted region in order to propose a possible involvement of specific genes in the clinical phenotype.


Nucleic acids and protein in brains and cerebella of rats transplacentally exposed to ethylnitrosourea.
Female rats were injected (IP) with either 15, 60, 100, or 150 mg/kg N-ethyl-N-nitrosourea (ENU) on gestation day 18. The neurochemical development of the whole brain and the cerebellum was studied in 21- and 60-day old offspring; pups from mothers subjected to 150 mg/kg were examined only at 21 days. Brain weights were significantly reduced in all ENU-exposed groups at 21 days, and the 60 mg/kg group at 60 days. Whole brain DNA and protein concentrations of most ENU groups were elevated at 21 days and RNA content and RNA/DNA ratios were subnormal. Deficits in whole brain DNA content were observed in all ENU groups on day 60. Cerebellar weight was reduced in the 60 and 150 mg/kg groups on day 21 and in the 100 mg/Kg group on day 60. At 21 days, reductions in cerebellar DNA and RNA concentrations and contents were often recorded in several ENU groups. Cerebellar DNA concentration and content of the 60 and 100 mg/kg groups remained subnormal at 60 days of age. In general, a dose-response effect was evident in the number and magnitude of neurochemical alterations produced by ENU. These data suggest that transplacental exposure to ENU, a potent neurotropic carcinogen, affects the biochemical maturation of the brain.


Is now the time for molecular driven therapy for diffuse large B-cell lymphoma?
Recent genetic and molecular discoveries regarding alterations in diffuse large B-cell lymphoma (DLBCL) deeply changed the approach to this lymphoproliferative disorder. Novel additional predictors of outcomes and new therapeutic strategies are being introduced to improve outcomes. Areas covered: This review aims to analyse the recent molecular discoveries in DLBCL, the rationale of novel molecular driven treatments and their impact on DLBCL prognosis, especially in ABC-DLBCL and High Grade B Cell Lymphoma. Pre-clinical and clinical evidences are reviewed to critically evaluate the novel DLBCL management strategies. Expert commentary: New insights in DLBCL molecular characteristics should guide the therapeutic approach; the results of the current studies which are investigating safety and efficacy of novel 'X-RCHOP' will probably lead, in future, to a cell of origin (COO) based upfront therapy. Moreover, it is necessary to identify early patients with DLBCL who carried MYC, BCL2 and/or BCL6 rearrangements double hit lymphomas (DHL) because they should not receive standard R-CHOP but high intensity treatment as reported in many retrospective studies. New prospective trials are needed to investigate the more appropriate treatment of DHL.


New insights into the genetics of congenital neutropenia.
Several congenital disorders may cause neutropenia. The recent advances in the field of molecular biology have facilitated our knowledge concerning pathophysiological mechanisms leading to these disorders. The molecular basis of disorders with defective myelopoiesis (severe congenital neutropenia and cyclic neutropenia) and disorders due to defective RNA processing (Shwachman Diamond syndrome and cartilage hair hypoplasia) are the two congenital neutropenia syndromes that are addressed in this review. Molecular defects defined by means of these disorders are very important for our understanding of the cause of the disorders as well as some unknown molecular mechanisms.


Siah-1 facilitates ubiquitination and degradation of factor inhibiting HIF-1alpha (FIH).
Hypoxia-inducible factor-1alpha (HIF-1alpha) has a central role in neuroprotective responses to hypoxia in the brain. Hydroxylation of HIF-1alpha by prolyl-hydroxylase PHD and aspargynyl-hydroxylase FIH (factor inhibiting HIF-1alpha) causes proteasomal degradation and transcriptional inhibition of HIF-1alpha. Siah ubiquitin ligases regulate the abundance of PHD via targeting for proteasomal degradation. The present study identified Siah-1 as a binding partner for another hydroxylase FIH. Siah-1 and FIH coimmunoprecipitated each other in mammalian cells. Siah-1 was found both to interact with the JmjC domain of FIH through its substrate-binding domain and to specifically ubiquitinate FIH via its RING finger domain. Siah-1 facilitated FIH degradation via the ubiquitin-proteasome pathway under hypoxic conditions. Such findings suggest that Siah ubiquitin ligases might play a role as up-stream regulators of both hydroxylases for HIF-1alpha, i.e., PHD and FIH, by targeting them for proteasomal degradation, leading to increased HIF-1alpha abundance, and transcriptional activity in hypoxia.


CD49f Can Act as a Biomarker for Local or Distant Recurrence in Breast Cancer.
Metastasis and local recurrence are the primary causes of treatment failure and patient death in breast cancer. The aim of this study was to validate a metastasis- and local recurrenceassociated biomarker for prognostic evaluation and planning treatment strategies. Formalin-fixed, paraffin-embedded tissues from a cohort of 312 patients (all stage II and III) were used. The prevalence of CD49f+ cells in the patients' tumors was analyzed and correlated with clinical characteristics to determine its prognostic and clinical implications. CD49f+ tumor cells were found in a minority of tumors, with 62.8% of the samples showing not a single cell of this subtype. In the clinical characteristics analysis, which were performed with t-tests, CD49f+ tumors were not associated with age, tumor size, World Health Organization grade, nodal status, human epidermal growth factor receptor 2 status, progesterone receptor status, or estrogen receptor status, although they were significantly associated with disease recurrence (distant metastasis or/and local recurrence). Univariate survival analysis using the Kaplan-Meier method showed that CD49f+ tumors were associated with markedly decreased disease-free survival (DFS); the same result was found using multivariate Cox analysis, even when only chemotherapy-treated patients were analyzed. Our results indicated that breast tumors with CD49f+ cancer cells are associated with an increased risk for disease recurrence after initial surgery with poor clinical outcomes (decreased DFS). Therefore, as it requires testing for only one additional protein, adding CD49f testing to conventional surgical pathology is a strategy that has great potential for prognostic and treatment-guidance purposes.


Factors of concern in a human 3D cellular airway model exposed to aerosols of nanoparticles.
Mucilair 3D bronchial airway models, cultured at an air-liquid interface, were exposed to aerosols of copper oxide (CuO) nanoparticles in Vitrocell air exposure modules. Four cell donors, four exposure modules and four exposure concentrations were varied within four different exposure sessions using a statistical experimental design called a hyper-Graeco-Latin square. Analysis of variance techniques were used to investigate the effects of these factors on release and RNA expression of inflammation markers monocyte chemoattractant protein-1 (MCP-1) interleukines 6 and 8 (IL-6 and IL-8) an cytotoxicity marker lactate dehydrogenase (LDH) determined 24h after exposure. The same techniques were also used to conduct a global analysis on RNA expressions of 10,000 genes. There were no major signs of cytotoxicity. Release of IL-6 and MCP-1 was affected by CuO concentration, and, for MCP-1, by donor variation. IL-8 release was not affected by these factors. However, gene expression of all three inflammation markers was strongly affected by CuO concentration but not by the other factors. Further, among the 10,000 genes involved in the global analysis of RNA expression, 1736 were affected by CuO concentration, 704 by donor variation and 269 by variation among exposure sessions. The statistical design permitted the assessment of the effect of CuO nanoparticles on 3D airway models independently of technical or experimental sources of variation. We recommend using such a design to address all potential sources of variation. This is especially recommended if test materials are expected to be less toxic than CuO, because the variation among the concentration levels could then be close to the variation among donors or exposure sessions.


Hybridization of Metal Nanoparticles with Metal-Organic Frameworks Using Protein as Amphiphilic Stabilizer.
Here, a facile strategy is reported to efficiently hybridize metal nanoparticles (MNPs) with typical metal-organic frameworks (MOFs) of ZIF-8 (zeolitic imidazolate framework-8), which employs bovine serum albumin (BSA, a serum albumin protein derived from cows) as the amphiphilic stabilizer to increase the affinity of MNP toward MOFs. For instance, the as-synthesized PdNPs/ZIF-8 composites with diameter from 100 to 200 nm always maintain well-defined crystalline structure, and the PdNPs with small size of ∼2 nm are well-dispersed in the crystal of MOFs without serious aggregations due to the BSA stabilizer. In Suzuki cross-coupling reactions of aryl halide, the PdNPs/ZIF-8 as catalysts have exhibited high activity and satisfied reusability owing to the use of BSA stabilizer as well as the fixing of MOFs matrixes. In addition, the strategy also can be extended to synthesize other kinds of MNPs/MOFs hybrid composites with tunable particle size, which brings more opportunity for functional MOFs hybrid materials.


Central role of the spleen in malaria parasite clearance.
In acute malaria, red blood cells (RBCs) that have been parasitized, but no longer contain a malaria parasite, are found in the circulation (ring-infected erythrocyte surface antigen [RESA]-RBCs). These are thought to arise by splenic removal of dead or damaged intraerythrocytic parasites and return of the intact RBCs to the circulation. In a study of 5 patients with acute falciparum malaria who had previously undergone splenectomy, it was found that none of these 5 patients had any circulating RESA-RBCs, in contrast to the uniform finding of RESA-RBCs in all patients with acute malaria and intact spleens. Parasite clearance after artesunate treatment was markedly prolonged, although the parasites appeared to be dead and could not be cultured ex vivo. These observations confirm the central role of the spleen in the clearance of parasitized RBCs after antimalarial treatment with an artemisinin derivative. Current criteria for high-grade antimalarial drug resistance that are based on changes in parasitemia are not appropriate for asplenic patients.


Enzymatic pretreatment of low-grade oils for biodiesel production.
The alkaline process for making biodiesel (fatty acid methyl esters, or FAME) is highly efficient at the transesterification of glycerides. However, its performance is poor when it comes to using oil that contain significant amounts of free fatty acids (FFA). The traditional approach to such feedstocks is to employ acid catalysis, which is slow and requires a large excess of methanol, or to evaporate FFA and convert that in a separate process. An attractive option would be to convert the FFA in oil feedstocks to FAME, before introducing it into the alkaline process. The high selectivity of enzyme catalysis makes it a suitable basis for such a pretreatment process. In this work, we present a characterization of the pretreatment of high-FFA rapeseed oil using immobilized Candida antarctica lipase B (Novozym 435), focused on the impact of initial FFA and methanol concentration. Based on experimental results, we have identified limitations for the process in terms of FFA concentration in the feedstock and make suggestions for process operation. It was found that, using 5% catalyst and 4% methanol at 35°C, the FFA concentration could be reduced to 0.5% within an hour for feedstock containing up to 15% FFA. Further, the reaction was observed to be under kinetic control, in that the biocatalyst converts FFA (and FAME) at a much higher rate than glyceride substrates. There is thus, both a minimum and a maximum reaction time for the process to achieve the desired concentration of FFA. Finally, an assessment of process stability in a continuous packed bed system indicates that as much as 15 m(3) oil could potentially be pretreated by 1 kg of biocatalyst at the given process conditions.


Topography of Neurons in the Rod Pathway of Human Retina.
The objective of this study was to map the distribution and density of the three major components of the classical scotopic "night vision" pathway (rods, rod bipolar, and AII amacrine cells) in postmortem human retinas. Four postmortem donor eyes (male and female, aged 44-56 years) were used to cut vertical sections through the temporal horizontal meridian. The sections were processed for immunohistochemistry and imaged using high-resolution multichannel confocal microscopy. Rods, rod bipolar, and AII amacrine cells were counted along the temporal horizontal meridian. Two additional retinas were used for intracellular injections. Rod peak density is close to 150,000 cells/mm2 at 4 to 5 mm (15° to 20°) eccentricity, declining to below 70,000 cells/mm2 in peripheral retina. Rod bipolar density is lower but follows a similar distribution with peak density near 10,000 cells/mm2 between 2 and 4 mm (7° to 15°) eccentricity declining to below 4000 cells/mm2 in peripheral retina. The peak density of AII amacrine cells (near 4000 cells/mm2) is located close to the fovea, at 0.5- to 2 mm-eccentricity (2° to 7°) and declines to below 1000 cells/mm2 in the periphery. Thus, convergence between rods and AII cells increases from central to peripheral retina. Comparison with human psychophysics and ganglion cell density indicates that the spatial resolution of scotopic vision is limited by the AII mosaic at eccentricities below 15° and by the midget ganglion cell mosaic at eccentricities above 15°.


Early maladaptive schemas and their relation to personality disorders: A correlational examination in a clinical population.
Personality disorder (PD) pathology has been linked to early maladaptive schemas (EMSs). Because of a large heterogeneity in study populations, sample size, statistical analyses and conceptualizations in the literature, the exact relationships between PDs and EMSs are still unclear. The current study examined the relationship between borderline, dependent, avoidant and obsessive-compulsive PDs, represented dimensionally as number of traits, and 15 different EMSs as measured by the Young Schema Questionnaire (YSQ). A total of N = 130 inpatients took part in the study (Mage = 43.6, gender = 51.5% female). Stepwise regressions indicated that borderline, dependent, avoidant and obsessive-compulsive PD traits were partly characterized by specific EMSs and EMSs grouped as domains (i.e., other-directedness domain for dependent PD and overvigilance for obsessive-compulsive PD) and that relations with a variety of domains and EMSs were overlapping for the PD dimensions (i.e., disconnection and rejection for both borderline and avoidant PDs). This suggests that PDs are reflected by a hybrid model of EMSs, with some EMSs and domains that relate to a broader vulnerability factor for PDs, and other domains that differentially relate to the independent PDs. Findings are informative for clinicians, as various EMSs per PD may be targeted in therapy.


Pharmacological adjuncts in the treatment of opioid and cocaine addicts.
Addiction consists of a complex neuropharmacologic behavioral cycle. The positive reinforcement of the drug and the negative reinforcement of withdrawal serve to drive the behavior of obtaining and ingesting the drug. The pharmacological adjuncts that are available today work by interfering with one or another part of the cycle. The alpha 2-adrenergic agonists, such as clonidine and guanabenz, act to block noradrenergic activity in the locus coeruleus and therefore block the negative reinforcement of opioid withdrawal. Naltrexone, on the other hand, works by preventing the positive reinforcement of administered opioids by preventing them from binding to the opioid receptor. In the case of cocaine addiction, most of the adjuncts currently in use focus on decreasing the severity of the immediate withdrawal symptoms. These agents potentiate dopaminergic transmission and in so doing tend to counter the dopamine depletion effect of prolonged cocaine use. Bromocriptine is the best known and probably the most effective member of this class. It may be that neuroleptics or naltrexone will prove to decrease reinforcement of cocaine use. However, the hazards of long-term neuroleptic use make it unlikely that they will be widely used for this purpose. Desipramine and perhaps other antidepressants may have a special role in treating cocaine addiction: They may prove to have some long-term prophylactic value and prevent relapse in recovering addicts. This ability may stem from the antidepressant action or it may involve a more specific action on dopaminergic transmission. These pharmacological agents may be very effective for certain purposes, such as relieving withdrawal symptoms. However, since they only act on one part of the addiction cycle, they can never be considered complete treatment by themselves. Of course, the use of all of these agents requires the voluntary cooperation of the patient. Therefore, the basis of the treatment of addictive illness continues to be the peer group and other types of interpersonal interactions. However, these pharmacological adjuncts may serve to make treatment easier, shorter and less expensive, and they may improve overall success rates. Consequently, they are of great value in the present and they can serve as models for the development of more effective agents in the future.


Chiral effects on the final step of an octahedron-shaped coordination capsule self-assembly.
The final step of the self-assembly of an octahedron-shaped coordination capsule was investigated by a novel theoretical method. Two different reaction pathways were detected and classified by the chiral types of constituents, which addressed the possibility of chiral effects on the self-assembly process.


Engage for Equity: Advancing the Fields of Community-Based Participatory Research and Community-engaged Research in Community Psychology and the Social Sciences.
Community Based Participatory Research (CBPR), as the most cited Community-Engaged Research (CEnR) approach in the health fields, mirrors community-psychology's long-term interest in participatory action research and community empowerment. This article introduces the Engage for Equity study, a long-term National Institutes of Health-funded inquiry to identify best partnering and collaborative practices that contribute to community capacity, empowerment and policy outcomes, and to long-term improved health and health equity. Four articles present facets of the study: psychometrics of partnering process and outcome measures, measures and outcomes of shared governance, and description of the CBPR Model as a new equity- and partnership based implementation framework; and as a tool for organizational learning and quality improvement. Finally a review of CBPR and CEnR in psychology offers recommendations for the field. Though focusing on CBPR and CEnR, Engage for Equity offers lessons for all forms of participatory action research.


Tongxie Anchang Decoction Relieves Visceral Hypersensitivity in Diarrhea-Predominant Irritable Bowel Syndrome Rats by Regulating the NGF/TrkA Signaling Pathway.
Irritable bowel syndrome (IBS) is a functional gastrointestinal disease characterized by visceral hypersensitivity-related abdominal pain, in which diarrhea-predominant IBS (IBS-D) is the main subtype and has a high clinical incidence. Tongxie Anchang Decoction (TXACD) has been proved to significantly improve abdominal pain in patients with IBS-D, but its underlying therapeutic mechanism still remains unclear. In the present study, IBS-D model rats were induced by neonatal maternal separation (NMS) combined with restraint stress (RS). The therapeutic effect of TXACD was evaluated by fecal characteristics and abdominal withdrawal reflex (AWR) scores. After 14 days of intragastric administration, the colonic tissues of rats were collected to detect the protein and gene level of the NGF, TrkA, and TRPV1 using Western blotting and real-time polymerase chain reaction, respectively, and detect mast cells infiltration using toluidine blue staining. The abdominal aorta blood centrifuged was collected for detecting serum levels of SP, 5-HT, and CGRP with ELISA. The results revealed that TXACD could significantly improve visceral hypersensitivity in IBS-D rats, reflected in the decrease of AWR score and the serum levels of SP, 5-HT, and CGRP. In addition, TXACD treatment could alleviate mast cells infiltration. Moreover, the expression levels of the NGF, TrkA, and TRPV1 were repressed by TXACD. The findings of the present study indicated that the therapeutic effect of TXACD on visceral hypersensitivity might be closely related to the downregulation of the NGF/TrkA signaling pathway, the reversal of TRPV1 expression and mast cells infiltration, and the decreased release of neuroendocrine factors SP, 5-HT, and CGRP.


[Effects of silicon on the ultrastructures of wheat radical cells under copper stress].
To explore the alleviation effect of silicon on wheat growth under copper stress, cultivar Aikang 58 was chosen as the experimental material. The growth, root activities and root tip ultrastructures of wheat seedlings, which were cultured in Hoagland nutrient solution with five different treatments (control, 15 mg x L(-1) Cu2+, 30 mg x L(-1) Cu2+, 15 mg x L(-1) Cu2+ and 50 mg x L(-1) silicon, 30 mg x L(-1) Cu2+ and 50 mg x L(-1) silicon), were fully analyzed. The results showed that root length, plant height and root activities of wheat seedlings were significantly restrained under the copper treatments compared with the control (P < 0.01), while these restraining effects were alleviated after adding silicon to copper-stress Hoagland nutrient solution. Under copper stress, the cell wall and cell membrane of wheat seedling root tips suffered to varying degrees of destruction, which caused the increase of intercellular space and the disappearance of some organelles. After adding silicon, the cell structure was maintained intact, although some cells and organelles were still slightly deformed compared with the control. In conclusion, exogenous silicon could alleviate the copper stress damages on wheat seedlings and cellular components to some extent.


The comparison of different protocols for expansion of umbilical-cord blood hematopoietic stem cells.
Hematopoiesis is maintained by the activity of multipotent stem cells, which have the dual capacity to self-renew and to differentiate into all of the blood cell lineages. The major challenge of stem cells based regenerative therapy is to expand ex vivo the primitive compartment to increase transplantable stem cells number. The present study was designed to evaluate several culture systems for in vitro maintenance of umbilical cord blood stem cells. The influences of different growth conditions such as stromal feeder layer, cytokines supplement and placental conditioned medium (PCM) have been evaluated over a relatively short period of time on CD34(+) cell expansion and maintenance of clonogenic progenitors. When cells were expanded on feeder layer in the presence of added cytokines and PCM on average a 2.96-fold increase of CD34(+)CD71(-) and a 3.13-fold increase of CD34(+)HLA-DR(-) was observed. The total number of colony forming cells (35 +/- 2.65) indicated also that the yield of clonogenic progenitors obtained with a combination of all factors was two folds higher than each of these factors alone and ten time above control (3.67 +/- 2.52). In conclusion, the results of our study clearly show that the ex vivo expansion of hematopoietic progenitor cells obtained from human umbilical cord blood is dependent on controlled experimental conditions, which might be helpful when designing culture systems for clinical applications.


[Health care to children and adolescents sheltered in Ribeirão Preto, SP].
This article aims to describe the health care offered to children and adolescents sheltered at the Care Center for Child and Adolescent Victims, in Ribeirão Preto-SP, Brazil. The study is descriptive and exploratory. Data were collected through semistructured interview, non-structured observation and document analysis. The points we examined were the human resource and physical space structure and the care delivered by the shelter and by the referral health unit. We observed many deficiencies, whose solutions not only depend on the shelter, but on an articulation with other sectors, seeking a quality health care that contemplates the needs of children and adolescents in their integrality.


Reanalysis of clause boundaries in Japanese as a constraint-driven process.
When processing the initial segment of a sentence, readers may favor an interpretation that will turn out to be incorrect as more words are read. In these cases, a reanalysis process is necessary in order to correct the mental representation built up to that point. It has been previously proposed that readers obey a minimum change restriction, as they prefer to change the mental representation as little as possible. The present paper reports two experiments in Japanese suggesting that a minimal change restriction is unnecessary to characterize reanalysis. It is proposed instead that the present data and previous observations are more naturally explained by a constraint-driven model in which revisions are performed only when required by parsing constraints.


The future of bisphosphonates in cancer.
Bisphosphonates, in conjunction with rehydration, are now the treatment of choice for hypercalcaemia of malignancy. They can also relieve bone pain and improve quality of life as single agent therapy and, in conjunction with systemic anticancer treatments, can prevent skeletal complications and slow down the metastatic process. The clinical effects are greatest and most clearly defined in breast cancer and multiple myeloma, but, theoretically, clinical benefit should be achievable across the entire spectrum of metastatic bone disease. The new biochemical markers for measuring bone resorption are for the first time providing a direct assessment of the effects of treatment on bone. It is hoped that they will enable a more scientific selection of the type, dose and schedule of bisphosphonate required for the best compromise between efficacy, convenience and patient acceptability. We can expect to see a rapid increase in the use of bisphosphonates in malignancy (especially breast cancer and myeloma). Careful assessment of the health-care economics of this new treatment modality is urgently needed.


Lycium barbarum polysaccharides ameliorate LPS-induced inflammation of RAW264.7 cells and modify the behavioral score of peritonitis mice.
In the present study, the anti-inflammatory effect of Lycium barbarum polysaccharide (LBP) and the possible molecular mechanism thereof were examined, so as to perceive the pharmacological action of LBP. With acute peritonitis in mice as the inflammatory model, the protective effect of LBP on peritonitis mice was evaluated by recording the effect of behavioral scores, studying the pathological damage of intestine and liver, and detecting the levels of inflammatory cytokines. Additionally, by establishing an lipopolysaccharide (LPS)-induced RAW264.7 macrophage model, the effect of LBP on RAW264.7 cell phenotype and culture supernatant inflammatory markers was observed. Finally, the activation of inflammation-related target genes, such as iNOS, Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB) p65, and IκBα, were further detected. The results reveal that pretreatment with LBP could decrease the behavioral score of inflammatory mice, inhibit the secretion of pro-inflammatory factors, and reduce liver and intestine injury. LBP can regulate the effect of lipopolysaccharide on the polarization of RAW264.7 cells, and reduce the production of NO and cytokines (TNF-α, IL-1β, IL-6). Further, LBP pretreatment was found to be able to significantly reduce the expression of iNOS, TLR4, NF-κB p65, and IκBα in macrophages. The present research provides evidence that LBP exerts potential anti-inflammatory activity in LPS-induced RAW264.7 macrophages via inhibiting TLR4 and NF-κB inflammatory sites and improving the behavior score of peritonitis mice. PRACTICAL APPLICATIONS: In recent years, the number of deaths worldwide has continued to rise as a result of inflammation. Despite said rise in deaths, many synthetic drugs with anti-inflammatory properties are significantly expensive and also have a host of side effects. Thus, the development of new anti-inflammatory drugs derived from medicinal plants has broad application potential. As such, in the present study, lipopolysaccharide (LPS)-induced macrophages were used to establish inflammatory cell models to verify the anti-inflammatory effect of Lycium barbarum polysaccharides (LBP). Findings were made that LBP could reduce the expression levels of inflammatory cytokines and NO by regulating macrophage polarization and NF-κB translocation, and thus, could exert anti-inflammatory activity. In addition, by intraperitoneal injection of LPS to establish peritonitis mice models, LBP pretreatment was found to have significantly modified the behavioral score of mice, while decreasing the secretion of inflammatory factors and the damage to several organs. The present study provides a basis for further understanding the effects of LBP in acute inflammation.


Value of autopsy in nonimmune hydrops fetalis: series of 51 stillborn fetuses.
Nonimmune hydrops fetalis (NIHF) is used to describe fetuses and newborns with generalized edema and cavity effusions. It is helpful to alert physicians about the presence of anemia, heart failure, and/or hypoproteinemia, but this diagnosis is frequently overlooked. We reviewed the autopsy files from 1990 to 2000, selected all cases with NIHF including clinical information (with maternal laboratory tests and ultrasound), and classified patients by etiology. Among 840 stillborn autopsies during the 11-year period, we found 51 with NIHF (6.07%). The clinical summary had mentioned hydrops in 14 patients and the etiology in another 7 by fetal ultrasonography, but without addressing the possibility of hydrops. In the remaining 30 cases neither hydrops nor an etiology was mentioned. Other pertinent diagnoses were maternal diabetes mellitus (4), congenital heart disease (3), and cystic hygroma (2). The following diagnoses were made in one instance each: cardiac tumor, twin transfusion syndrome, congenital adenomatoid malformation, syphilis, Turner syndrome, and cerebral arteriovenous malformation. Postmortem and placental examination confirmed the following etiologies: congenital infections (17); placental pathology significant enough to explain NIHF (10); cardiovascular diseases (8) (further classified as congenital heart disease [3], rhabdomyoma [1], and vascular malformations [4]); chromosomal abnormalities (6); uncontrolled maternal diabetes (4); intrathoracic lesions (2); prune-belly syndrome (2); and idiopathic NIHF (2). Only 3.9% of the cases studied had no identifiable etiology. The cause of hydrops was confirmed by autopsy in 47 fetuses (92%), which further supports the importance of performing an autopsy. Thirty-two cases (62.74%) had placental abnormalities helpful to the etiology (parvovirus, syphilis, Turner's syndrome, etc.). In 20 instances, the clinical summary had no mention of either hydrops or any of the diseases leading to it. The autopsy in conjunction with placental examination and fetal ultrasound represent the best combination to determine the etiology of NIHF among stillborn fetuses.


Unusual manifestations of cushing's syndrome in a multiple endocrine neoplasia type I kindred.
To describe two unusual cases of Cushing's syndrome in a kindred with multiple endocrine neoplasia type I (MEN I). The clinical and laboratory data as well as follow-up course of the two patients are reviewed in detail. Our first patient with a history of MEN I had hypercortisolism and computed tomographic evidence of a right adrenal mass (8.5 by 11 cm) extending into the inferior vena cava as well as multiple pulmonary nodules. He was diagnosed with Cushing's syndrome attributable to metastatic adrenal cancer that progressed despite chemotherapy. He died 2 years later. His son, who was also diagnosed with MEN I, had adrenocorticotropic hormone-dependent Cushing's syndrome. The plasma corticotropin-releasing hormone (CRH) level was high; magnetic resonance imaging showed normal pituitary findings but an islet cell tumor of the pancreas. The islet cell tumor was resected, and the patient's urinary cortisol declined to upper limits of normal. CRH was detected in the tissue, and the patient was thought to have Cushing's syndrome as a result of a CRH-secreting islet cell tumor. One year later, however, his Cushing's syndrome recurred. Inferior petrosal sinus sampling suggested a pituitary source, and the patient underwent transsphenoidal hypophysectomy. Histopathologic examination did not reveal pituitary hyperplasia or microadenoma, but the patient was cured of his Cushing's syndrome. Cushing's syndrome is a rare initial manifestation of MEN I. We report two unusual causes of Cushing's syndrome in MEN I--that is, adrenal cancer and a probable CRH-secreting islet cell tumor. The natural history of Cushing's syndrome in MEN I is not known; further studies should be conducted.


Antioxidant activity of dodecyl gallate.
Dodecyl (C12) gallate exhibits both potent chain-breaking and preventive antioxidant activity. The pyrogallol moiety is responsible for both activities. Dodecyl (lauryl) gallate prevents generation of superoxide radicals by xanthine oxidase, and this activity comes from its ability to inhibit the enzyme. The inhibition kinetics analyzed by Lineweaver-Burk plots found that dodecylgallate is a noncompetitive inhibitor for the generation of superoxide anion. Dodecyl gallate also inhibits formation of uric acid. The inhibition kinetics analyzed by Lineweaver-Burk plots found that dodecyl gallate is a competitive inhibitor for this oxidation. Mitochondrial lipid peroxidation induced by Fe(III)-adenosine 5'-diphosphate/reduced nicotinamide adenine dinucleotide was inhibited by dodecyl gallate while its parent compound, gallic acid, did not show this inhibitory activity. Dodecyl gallate protected mitochondrial functions and human red blood cells against oxidative stresses, but gallic acid showed little effect. The hydrophobic dodecyl group is largely associated with the preventive antioxidative activity.


The use of medical grade honey in clinical practice.
In the current healthcare environment, clinicians are increasingly under pressure to use wound care products that are cost-effective. This includes products that can be used in a variety of wounds to achieve different outcomes, depending on the wound-bed requirements. Medical grade honey has emerged as a product that can achieve a variety of outcomes within the wound and is safe and easy to use. This article reviews the use of a medical grade honey (Medihoney) in various clinical applications, with a view to placement on the wound care formulary in both primary and secondary care. It provides an in-depth account of case studies featured in a poster presentation at the 2008 European Wound Management Association meeting in Lisbon, Portugal.


Effects of OKM5, a monoclonal antibody to glycoprotein IV, on platelet aggregation and thrombospondin surface expression.
The monoclonal antibody, OKM5, recognizes an 88-Kd monocyte membrane protein and also binds to the platelet membrane protein, GPIV (GPIIIb, CD36). In this study, we have found that the OKM5 target epitope is present at approximately 12,000 copies per platelet and that interaction with the antibody has both stimulatory and inhibitory effects on platelet function. In the absence of other stimuli, OKM5 induced platelet aggregation, secretion, and expression of fibrinogen receptors. These stimulatory responses required intact antibody as F(ab')2 fragments were not active but blocked the stimulatory activity of the intact antibody. In contrast, exposure of platelets to OKM5 followed by another strong stimulus such as thrombin resulted in a marked suppression of fibrinogen, fibronectin, and von Willebrand factor binding to the cells. This effect was not noted when a weak stimulus, adenosine diphosphate, was the second agonist. At OKM5 concentrations that interfered with fibrinogen binding to thrombin-stimulated platelets by 80% to 90%, platelet binding of exogenous thrombospondin, or surface expression of endogenous thrombospondin was not affected. The inhibitory effect of OKM5 on fibrinogen binding to thrombin-stimulated platelets was related to the formation of massive platelet aggregates in the samples. These results show that interaction of OKM5 with its target antigen on platelets can elicit diverse functional responses from the cells.


[Evaluation of brain-targeted trendence of scutellarin nasal administration].
To evaluate the feasibility of developing brain-targeted nasal delivery system of scutellarin by the passage between nase and brain in nasal olfactory area. The samples of cerebrospinal fluid (CSF) and blood were prepared by cranial puncture and femoral artery catheterization methods respectively according to the certain sampling time after drug administered. The scuteIlarin concentration of samples were determined by 125 marked method. Pharmacokinetic parameters were calculated by trapezoidal rule. The brain-targeted trendence were evaluated by the value of the index AUC(brain)/AUC(plasma). The distribution of scutellarin in brain following intranasal administration was different between tissues. Drug concentration in olfactory bulb achieved to peak at 5-15 min after intranasal administration, while in brain tissue was 30-60 min. Above all, peak concentration in olfactory bulb and olfactory region respectively were (574.8 +/- 205.), (323.4 +/- 128.3) ng x g(-10, both are higher than CSF, which is (123.2 +/- 29.3) ng x g(-1). Moreover, the distribution of scutellarin given by intranasally in brain was: olfactory bulb (OB) >> olfactory region (OR) > cerebrospinal fluid (CSF) > cerebellum(CB) > medulla oblongata (MO) > cerebrum (CR); AUC(0-240) of olfactory bulb, olfactory region and CSF after scutellarin intranasal administration were 5.54, 5.07 and 5.51 times of that after intravenous injection, respectively. And the AUC(0-240) of other brain tissues after intranasal administration were also higher than that after intravenous injection. AUC(brain tissue)/ AUC(plasma) of every brain tissues by intranasally are all higher than that by intravenously remarkably. For instance, 5 min after intranasal administration, the value of AUC(CSF)/ AUC(plasma), AUC(OB)/AUC(plasma), and AUC(CR)/AUC(plasma) were 30.34, 56.93, and 6.14 times of that by intravenously. Part of scutellarin could be straightly transported into brain by the intranasal administration. Its absorption pathway was: the molecule of Scutellarin throughed olfactory mucosa in nasal cavity into olfactory bulb in arachno-hypostegal cavity, and then entered into olfactory region, CSF, cerebrum and cerebellum gradually. It showed that olfactory bulb was the only way for drug molecule to go through nasal cavity into brain. It had a significant trendence of brain-targeted when compared to oral administration and intravenous injection, which indicated a certain feasibility to develop a brain-targeted nasal delivery system for scutellarin.


Squeaking Is Common and Increases Over Time Among Patients With Long-term Follow-up After Ceramic-on-ceramic THA.
Ceramic-on-ceramic (CoC) is a durable bearing with excellent wear characteristics, but squeaking remains a concern. The proportion of patients who report squeaking varies widely between studies performed at short- and mid-term follow-up. (1) What proportion of patients treated with CoC THA bearings report squeaking at a minimum of 10 years of follow-up? (2) Are patient, implant, or radiographic factors associated with squeaking? (3) Are THAs that squeak more likely to be revised than those that do not? (4) Are patient-reported functional outcome scores lower between THAs that squeak and THAs that do not squeak at long-term follow-up? Between January 1, 2003 and August 31, 2008 a total of 80 patients received THAs with third-generation alumina-on-alumina bearings at one center. Of the original 80 patients, 1% (1 of 80) had died, and 21% (17 of 80) were lost to follow-up before 10 years, leaving 62 patients for analysis at a median (range) of 14 years (11 to 16). Ceramic-on-ceramic THA represented 23% (80 of 343) of all primary THAs performed during the study period. Ceramic-on-ceramic THA was used preferentially in patients younger than 50 years of age. The mean (range) age of patients in the cohort was 44 ± 11 years (18 to 65). Sixty-eight percent (42 of 62) were men. Two separate manufacturers' implants were included. There were uncemented acetabular and femoral components included in this study. All CoC bearings were third-generation alumina-on-alumina. Squeaking was determined through a mailed questionnaire or telephone interview. The 10-question survey developed by the researchers queried patients whether audible "squeaking" could be heard from their hip replacement. Patients were asked to write in their description of the noise to distinguish squeaking from other noises not relevant to the current study. Implant information, component position, and patient demographics were obtained via chart review and postoperative radiographs reviewed by one of the investigators not involved with the index operative procedure. Using revision for any reason as an endpoint, a Kaplan-Meier analysis was performed to compare survivorship between THAs that squeaked versus those that did not. Patient-reported outcomes were surveyed using the Hip Disability and Osteoarthritis Outcome Score for Joint Replacement (HOOS JR), which comprises six items regarding patient pain and function, raw summed scores range from 0 (perfect hip health) to 24 (total hip disability). Squeaking was self-reported by 53% (33 of 62) of patients in this group. Squeaking was more common in patients who received the titanium-molybdenum-zirconium-iron stem than in patients with the titanium-aluminum-vanadium stem (63% [29 of 46] versus 31% [4 of 13]; odds ratio 3.8 [95% CI 1.02 to 14.4]; p = 0.046). We found no differences in the likelihood a patient would report squeaking based on component position, component size, patient age, sex, or BMI. Ten-year survivorship free from revision was not lower in patients who reported squeaking (91% [95% CI 74 to 97] versus 90% [95% CI 71 to 96]; p = 0.69). Patient-reported outcome scores (HOOS JR) were not lower in those who reported squeaking (3 ± 3 [95% CI 1.5 to 4.0] versus 3 ± 5 [95% CI 1.5 to 5.5]; p = 0.59). At long-term follow-up, we found that CoC bearing squeaking in patients who underwent THA is more common than previously reported. Survivorship was lower than expected in this cohort, and most revisions in this series were for squeaking. Although implant-dependent, surgeons should counsel patients about the potential for squeaking in CoC THA, which may occur years after index procedure. Level III, therapeutic study.


Specific Role for Yeast Homologs of the Diamond Blackfan Anemia-associated Rps19 Protein in Ribosome Synthesis.
Approximately 25% of cases of Diamond Blackfan anemia, a severe hypoplastic anemia, are linked to heterozygous mutations in the gene encoding ribosomal protein S19 that result in haploinsufficiency for this protein. Here we show that deletion of either of the two genes encoding Rps19 in yeast severely affects the production of 40 S ribosomal subunits. Rps19 is an essential protein that is strictly required for maturation of the 3'-end of 18 S rRNA. Depletion of Rps19 results in the accumulation of aberrant pre-40 S particles retained in the nucleus that fail to associate with pre-ribosomal factors involved in late maturation steps, including Enp1, Tsr1, and Rio2. When introduced in yeast Rps19, amino acid substitutions found in Diamond Blackfan anemia patients induce defects in the processing of the pre-rRNA similar to those observed in cells under-expressing Rps19. These results uncover a pivotal role of Rps19 in the assembly and maturation of the pre-40 S particles and demonstrate for the first time the effect of Diamond Blackfan anemia-associated mutations on the function of Rps19, strongly connecting the pathology to ribosome biogenesis.


The presence of aggression cues inverts the relation between digit ratio (2D:4D) and prosocial behaviour in a dictator game.
Digit ratio (2D:4D) is a sexually dimorphic trait. Men have relatively shorter index (2D) compared to ring (4D) fingers than women. More masculine ratios are thought to be influenced by higher prenatal testosterone levels. In the present paper, we aim to show the context-dependency of the relation between 2D:4D and social behaviour. In two studies, we expose participants either to control or to aggression cues. Afterwards, they make a decision in a dictator game. Participants with low 2D:4D showed higher allocation levels (i.e. they were more prosocial) than participants with high 2D:4D in a neutral situation. However, this relationship inverts after exposure to an aggression cue. It turns out that in high 2D:4D people, aggression cues even increase prosocial behaviour. We call for future research which focuses on other plausible interactions between 2D:4D and context cues rather than on linear relations.


Opposite diastolic effects of omecamtiv mecarbil versus dobutamine and ivabradine co-treatment in pigs with acute ischemic heart failure.
Acute ischemic cardiogenic shock is associated with poor prognosis, and the impact of inotropic support on diastolic function in this context is unclear. We assessed two suggested new inotropic strategies in a clinically relevant pig model of ischemic acute heart failure (AHF): treatment with the myosin activator omecamtiv mecarbil (OM) or dobutamine and ivabradine (D+I). Left ventricular (LV) ischemia was induced in anesthetized pigs by coronary microembolization (n = 12). The animals then received OM (bolus 0.75 mg/kg, followed by 0.5 mg/kg per h) (n = 6) or D+I (5 μg/kg per min + 0.29 ± 0.16 mg/kg) (n = 6), respectively. Ischemia reduced the stroke volume (SV), despite the increased left atrial pressure associated with impaired LV early relaxation, systolic dilatation, and LV late diastolic stiffness. Both treatments improved systolic ejection, but only D+I increased the SV from 26 ± 5 to 33 ± 5 mL. D+I enhanced LV early relaxation (Tau; from 45 ± 11 to 29 ± 4 msec) and prolonged the diastolic time (DT) from 338 ± 60 to 352 ± 40 msec. In contrast, OM prolonged Tau (42 ± 5 to 62 ± 10 msec) and shortened the DT (from 326 ± 68 to 248 ± 84 msec). Our data suggest that enhanced early relaxation by D+I improves LV pump function in postischemic acute heart failure. In contrast, OM worsened lusitropy in this model.


Tumor necrosis factor alpha induces expression of human immunodeficiency virus in a chronically infected T-cell clone.
Tumor necrosis factor alpha (TNF-alpha), also known as cachectin, was demonstrated to induce the expression of human immunodeficiency virus (HIV) in a chronically infected T-cell clone (ACH-2). Concentrations of recombinant TNF-alpha as low as 50 pg/ml induced a significant increase over background of HIV expression in the ACH-2 cells as determined by supernatant reverse transcriptase activity. The HIV-inducing effects of TNF-alpha could not be explained by toxic effects on the cells. In addition, both the uninfected parental cell line (A3.01) and the infected ACH-2 cells were shown to have high-affinity receptors for TNF-alpha. Transient-transfection experiments demonstrated that the inductive effects of TNF-alpha were due to specific activation of the HIV long terminal repeat. These studies provide evidence that TNF-alpha may play a role in the mechanisms of pathogenesis of HIV infection.


Chronic mucocutaneous candidiasis: a case report.
Chronic mucocutaneous candidiasis is a immuno deficiency disorder primarily due to T cell dysfunction characterized by persistent candidal infection of mucous membrane, skin, scalp and nails. Chronic mucous membrane candidiasis has an onset in infancy or childhood; the primary affected site is the oral cavity; however, lesions may occur on trunk, hands, feet and scalp. This paper describes a 12-year-old girl with candidial infection of the oral mucosa and extra oral involvement of fingers, nails, toes and intertragus area.


Coil embolization of renal artery bifurcation and branch aneurysms with flow preservation.
Coil embolization is one of the most common endovascular approaches to treatment of renal artery aneurysms (RAAs). The purpose of this retrospective study was to compare complications, mortality, and morbidity associated with sac packing, coil trapping, and inflow occlusion. The records of all patients with RAAs treated with coil embolization at our center from June 2003 to May 2017 were retrospectively reviewed. Demographics of the patients, aneurysm characteristics, management strategies, perioperative and long-term outcomes, and complications were analyzed. A total of 52 patient records were reviewed; 28 patients received sac packing and 24 patients underwent coil trapping/inflow occlusion. There was no significant difference in patients' demographics or RAA characteristics between the groups. The mean aneurysm diameter was 25.6 ± 8.4 mm in the sac packing group and 31.1 ± 16.8 mm in the coil trapping/inflow occlusion group (P = .130). Most aneurysms in the sac packing group originated from the main renal artery bifurcation (67.9%), whereas in the coil trapping/inflow occlusion group, most aneurysms originated from the renal segmental branch arteries (54.2%). The immediate technical success rate was 100%, and the in-hospital mortality rate was 0% in both groups. Sac packing was more likely to be associated with endoleak immediately after the procedure (28.6% vs 8.3%; P = .065). The overall perioperative complication rate was not statistically different between the groups (7.1% vs 16.7%; P = .284). The mean duration of follow-up was 37.67 ± 29.84 months and 49.35 ± 28.11 months in the sac packing and coil trapping/inflow occlusion groups, respectively (P = .192). No deaths related to RAAs or aneurysm rupture occurred in either group. The overall morbidity rate was similar between groups (12.5% vs 25%; P = .284). Partial renal infarction occurred in two and five patients in the sac packing and coil trapping/inflow occlusion groups, respectively (8.3% vs 25%; P = .132). Impaired renal function was more frequent after coil trapping/inflow occlusion (0% vs 15%; P = .049). A single patient in the sac packing group required further intervention for reperfusion of the aneurysmal sac at 4 months (4.2% vs 0%; P = .356). Sac packing might be a safe and effective way to treat RAAs located at the main bifurcation or in branch arteries and may be preferable to coil trapping/inflow occlusion, considering the potential loss of functional renal mass.


Biochemical properties of urea transporters.
Urea and urea transporters (UT) are critical to the production of concentrated urine and hence in maintaining body fluid balance. The UT-A1 urea transporter is the major and most important UT isoform in the kidney. Native UT-A1, expressed in the terminal inner medullary collecting duct (IMCD) epithelial cells, is a glycosylated protein with two glycoforms of 117 and 97 kDa. Vasopressin is the major hormone in vivo that rapidly increases urea permeability in the IMCD through increases in phosphorylation and apical plasma-membrane accumulation of UT-A1. The cell signaling pathway for vasopressin-mediated UT-A1 phosphorylation and activity involves two cAMP-dependent signaling pathways: protein kinase A (PKA) and exchange protein activated by cAMP (Epac). In this chapter, we will discuss UT-A1 regulation by phosphorylation, ubiquitination, and glycosylation.


10 years of controversy, twists and turns in the Perruche wrongful life claim: compensation for children born with a disability in France.
Since March 1st, 2010, French citizens have been able to call on a new legal procedure for defending their rights: the priority preliminary ruling on issues of constitutionality (question prioritaire de constitutionnalité, QPC). If, during a trial, a citizen considers that a provision of the applicable law is inconsistent with the Constitution of the French Republic, he/she may request that the matter be referred to the Constitutional Council. One ofthe first QPCs concerned legislation related to the Perruche jurisprudence. In a ruling on November 17th, 2000, the French Supreme Court of Appeal had granted the child Nicolas Perruche the right to financial compensation for the material costs related to his physical disability (caused by congenital rubella). In response, Article 1 of the Patients' Rights and Quality of Care Act (passed on March 4th, 2002) prohibited the award of compensation to a child "just because he/she has been born [with a disability]", i.e. in "wrongful life" claims. Since the enactment of the Act, compensation in a case like Perruche may only be awarded to cover the parents' psychological suffering, rather than the child's status at birth. The application of this "anti-wrongful life claim" legislation has since been subject of heated debate. In a QPC ruling on June 11th, 2010, the Constitutional Council found that Article 1 of the Patients' Rights and Quality of Care Act was (with the exception of its transitional provisions) indeed consistent with the Constitution of the French Republic.


DNA demethylation and USF regulate the meiosis-specific expression of the mouse Miwi.
Miwi, a member of the Argonaute family, is required for initiating spermiogenesis; however, the mechanisms that regulate the expression of the Miwi gene remain unknown. By mutation analysis and transgenic models, we identified a 303 bp proximal promoter region of the mouse Miwi gene, which controls specific expression from midpachytene spermatocytes to round spermatids during meiosis. We characterized the binding sites of transcription factors NF-Y (Nuclear Factor Y) and USF (Upstream Stimulatory Factor) within the core promoter and found that both factors specifically bind to and activate the Miwi promoter. Methylation profiling of three CpG islands within the proximal promoter reveals a markedly inverse correlation between the methylation status of the CpG islands and germ cell type-specific expression of Miwi. CpG methylation at the USF-binding site within the E2 box in the promoter inhibits the binding of USF. Transgenic Miwi-EGFP and endogenous Miwi reveal a subcellular co-localization pattern in the germ cells of the Miwi-EGFP transgenic mouse. Furthermore, the DNA methylation profile of the Miwi promoter-driven transgene is consistent with that of the endogenous Miwi promoter, indicating that Miwi transgene is epigenetically modified through methylation in vivo to ensure its spatio-temporal expression. Our findings suggest that USF controls Miwi expression from midpachytene spermatocytes to round spermatids through methylation-mediated regulation. This work identifies an epigenetic regulation mechanism for the spatio-temporal expression of mouse Miwi during spermatogenesis.


Preventing, assessing and treating skin tears.
Skin tears are acute wounds caused by mechanical forces resulting in the separation of the skin's outer layers. Skin tears are more likely to occur in vulnerable people such as older people and people with neurodegenerative conditions. Rising life expectancy means that the number of patients with skin tears is expected to increase. This article describes the characteristics of skin tears, details the risk factors for skin tears and explains the importance of using a holistic, evidence-based and person-centred approach to skin tear prevention, assessment and treatment. The article outlines the crucial role of nurses as part of the multidisciplinary team in the management of skin tears.


Choosing a Side: Clinician Perspective Taking in Ethics Consultations.
AbstractEthics consultation is a service provided to patients, families, and clinicians to support decisions during ethical dilemmas. This study is a secondary qualitative analysis of 48 interviews from clinicians involved in an ethics consultation at a large academic health center. An inductive secondary analysis of this data set led to the emergence of one key theme, the apparent perspective the clinicians adopted as they recalled a specific ethics case. This article presents a qualitative analysis of the propensity of clinicians involved in an ethics consultation to adopt the subjective viewpoints of their team, their patient, or both simultaneously. Clinicians demonstrated an ability to take the patient perspective (42%), the clinician perspective (31%), or the clinician-patient perspective (25%). Our analysis suggests the potential for narrative medicine to build the empathy and moral imagination necessary to bridge the gap in perspectives between key stakeholders.


Exercise suppresses tumor growth independent of high fat food intake and associated immune dysfunction.
Epidemiological data suggest that exercise training protects from cancer independent of BMI. Here, we aimed to elucidate mechanisms involved in voluntary wheel running-dependent control of tumor growth across chow and high-fat diets. Access to running wheels decreased tumor growth in B16F10 tumor-bearing on chow (- 50%) or high-fat diets (- 75%, p < 0.001), however, tumor growth was augmented in high-fat fed mice (+ 53%, p < 0.001). Tumor growth correlated with serum glucose (p < 0.01), leptin (p < 0.01), and ghrelin levels (p < 0.01), but not with serum insulin levels. Voluntary wheel running increased immune recognition of tumors as determined by microarray analysis and gene expression analysis of markers of macrophages, NK and T cells, but the induction of markers of macrophages and NK cells was attenuated with high-fat feeding. Moreover, we found that the regulator of innate immunity, ZBP1, was induced by wheel running, attenuated by high-fat feeding and associated with innate immune recognition in the B16F10 tumors. We observed no effects of ZBP1 on cell cycle arrest, or exercise-regulated necrosis in the tumors of running mice. Taken together, our data support epidemiological findings showing that exercise suppresses tumor growth independent of BMI, however, our data suggest that high-fat feeding attenuates exercise-mediated immune recognition of tumors.


[Diagnosis of aphasia on the stroke unit].
The first weeks of aphasia are called the acute stage. The rapid change and possible fluctuation of language deficits at that stage as well as concurrent phenomena such as drive disturbances, apraxia, or perseveration pose particular requirements for aphasia diagnosis. Professional language diagnosis in a stroke unit is necessary for detailed description of the language deficits, differential diagnosis of concomitant cognitive or functional disturbances, and a description of the dynamics of the deficits to start with specific therapeutical interventions as soon as the patient's health status allows. There are three published German aphasia test batteries especially constructed for diagnosis of acute aphasia language deficits. They differ with respect to content and pragmatic aspects and offer a range of applications, including the diagnosis of aphasia, recommendations for therapy, and the use in scientific studies.


Tyrosine kinase and control of cell proliferation.
The usefulness of phosphotyrosine antibodies for the detection of physiologically regulated or deregulated tyrosine kinases is discussed in this report. This rather rare enzymatic activity is shared by receptors for some polypeptide growth factors and by the products of Class 1 oncogenes. The antibodies are able to detect proteins phosphorylated on tyrosine in fibroblasts stimulated with growth factors such as EGF and PDGF. The major phosphorylated protein species are the receptors themselves, which undergo phosphorylation only after the addition of the exogenous factor and only transiently. Phosphotyrosine antibodies were able to detect the products of the retroviral Class 1 oncogenes, which are endowed with deregulated tyrosine kinase activity. In fact, in these cases a constitutive phosphorylation of the relevant proteins was observed, which occurred continuously and independently of the presence or lack of exogenous ligands. A tyrosine kinase constitutively activated in human gastric carcinoma cells was detected by P-Tyr antibodies. This molecule has been characterized at the molecular level, and the mechanisms responsible for its enzymatic activation have been investigated. The question of whether the tyrosine kinase identified is responsible for the induction and the maintenance of the transformed phenotype in gastric carcinomas remains to be answered. It is reasonable to suggest that this might be the case by analogy with other situations such as Class 1 oncogenes activated by transduction by retroviruses, abnormal expression of EGF receptors, or deregulated activity of c-abl-encoded proteins in chronic myelogenous leukemia and acute lymphoblastic leukemia. Thus, the search for deregulated kinases by means of phosphotyrosine antibodies seems to be useful for identifying new activated oncogenes in clinical oncology.


Acute phase proteins as protective factors against the toxicity of tumor necrosis factor.
Tumor Necrosis Factor is an endogenous messenger molecule (cytokine) exhibiting a broad range of biological activities. Of special interest is its cytotoxic activity, specific for transformed tumor cells and which results in outspoken tumor regression in experimental animals. Administration of high dose of TNF, necessary to treat internal tumors, however is currently impossible because of the pro-inflammatory properties of TNF. Injection of TNF causes significant decrease in blood pressure and serious liver-toxicity. However, the liver is not only a target organ for TNF, it also produces protecting factors. Based on our studies of the role of Interleukin-1 and Interleukin-6, two other cytokines, we investigated the protective role of a set of liver-derived proteins, the acute phase proteins. We identified two such proteins as protective factors in our mouse models: alpha-1-Acid Glycoprotein (AGP) and alpha-1-Antitrypsin (AT). Both proteins confer complete protection against TNF-induced lethality in mouse models, and are currently evaluated as adjuvans in TNF-based antitumor therapy. The protection by both proteins also brought us new insights in the mechanism of TNF-induced liver-toxicity. In this sense, molecules like elastase and Platelet Activating Factor were recognized as mediating factors.


Real-world outcomes of ledipasvir/sofosbuvir in treatment-naive patients with hepatitis C.
Studies of hepatitis C virus (HCV) regimens have documented substantially reduced effectiveness in sustained virologic response (SVR) in the context of real-world clinical practice compared with clinical trials. Real-world and clinical trial SVR and cost-per-SVR data have not been reported for the all-oral, peginterferon-free and ribavirin (RBV)-free ledipasvir/sofosbuvir (LDV/SOF) regimen. Our objective was to compare the rates of SVR achievement and cost per SVR between pooled data from clinical studies of LDV/SOF and from real-world clinical practice. Data were derived from the Hepatitis C Therapeutic Registry and Research Network (HCV-TARGET), a real-world, multicenter, prospective, observational study; and from the TRIO Network, a retrospective database of HCV-treated patients. The 1-year cost per SVR was calculated as the total cost of an SVR ([cost of treatment regimen, adverse events, and monitoring costs] per SVR) during the first year of treatment. After 12 weeks, the SVR rates obtained in real-world studies ranged from 94% to 98%, comparing favorably with the SVRs achieved in the ION-1 and ION-3 trials (94% and 95%-99% with 8 and 12 weeks of RBV-free therapy, respectively). A single SVR, on average, cost $84,989 among patients enrolled in the ION-3 trial, with higher costs ($101,204) among patients with compensated cirrhosis compared with noncirrhotic patients ($81,668). In the pooled TARGET/TRIO population, the average cost of an SVR was $84,770, with costs of $101,380 and $81,368 in patients with compensated cirrhosis and patients without cirrhosis, respectively. Unlike the results obtained with prior HCV regimens, this study suggests that similar SVR rates are achieved with LDV/SOF in clinical trial-based studies and real-world studies. Further, achieving an SVR in real-world clinical practice was not associated with excess costs.


Effects of glucose homeostasis on protein metabolism in patients with advanced chronic kidney disease.
Insulin deficiency is known to be associated with a state of increased muscle protein breakdown; this process is mediated by the ubiquitin-proteasome pathway. Convincing in vitro data are further supported by extensive studies in humans with insulin deprivation and are further substantiated by reversal of muscle protein breakdown with insulin treatment. In patients with end-stage renal disease (ESRD) and diabetes mellitus (DM), muscle protein breakdown is enhanced in both acute and chronic conditions. Recent data also point to the potential protein catabolic effects of insulin resistance combined with insulin deficiency. Because ESRD is associated with a state of insulin resistance, uremic muscle wasting may also be mediated by this pathway.


Commissioning a 250 MeV research beamline for proton FLASH radiotherapy preclinical experiments.
The potential reduction of normal tissue toxicities during FLASH radiotherapy (FLASH-RT) has inspired many efforts to investigate its underlying mechanism and to translate it into the clinic. Such investigations require experimental platforms of FLASH-RT capabilities. To commission and characterize a 250 MeV proton research beamline with a saturated nozzle monitor ionization chamber for proton FLASH-RT small animal experiments. A 2D strip ionization chamber array (SICA) with high spatiotemporal resolution was used to measure spot dwell times under various beam currents and to quantify dose rates for various field sizes. An Advanced Markus chamber and a Faraday cup were irradiated with spot-scanned uniform fields and nozzle currents from 50 to 215 nA to investigate dose scaling relations. The SICA detector was set up upstream to establish a correlation between SICA signal and delivered dose at isocenter to serve as an in vivo dosimeter and monitor the delivered dose rate. Two off-the-shelf brass blocks were used as apertures to shape the dose laterally. Dose profiles in 2D were measured with an amorphous silicon detector array at a low current of 2 nA and validated with Gafchromic films EBT-XD at high currents of up to 215 nA. Spot dwell times become asymptotically constant as a function of the requested beam current at the nozzle of greater than 30 nA due to the saturation of monitor ionization chamber (MIC). With a saturated nozzle MIC, the delivered dose is always greater than the planned dose, but the desired dose can be achieved by scaling the MU of the field. The delivered doses exhibit excellent linearity with R 2 > 0.99 ${R^2} > 0.99$ with respect to MU, beam current, and the product of MU and beam current. If the total number of spots is less than 100 at a nozzle current of 215 nA, a field-averaged dose rate greater than 40 Gy/s can be achieved. The SICA-based in vivo dosimetry system achieved excellent estimates of the delivered dose with an average (maximum) deviation of 0.02 Gy (0.05 Gy) over a range of delivered doses from 3 to 44 Gy. Using brass aperture blocks reduced the 80%-20% penumbra by 64% from 7.55 to 2.75 mm. The 2D dose profiles measured by the Phoenix detector at 2 nA and the EBT-XD film at 215 nA showed great agreement, with a gamma passing rate of 95.99% using 1 mm/2% criterion. A 250 MeV proton research beamline was successfully commissioned and characterized. Challenges due to the saturated monitor ionization chamber were mitigated by scaling MU and using an in vivo dosimetry system. A simple aperture system was designed and validated to provide sharp dose fall-off for small animal experiments. This experience can serve as a foundation for other centers interested in implementing FLASH radiotherapy preclinical research, especially those equipped with a similar saturated MIC.


Insulinomas derived from hyperplastic intra-hepatic islet transplants.
Insulinomas were induced in a new animal model by transplanting a low number of isologous pancreatic islets via the portal vein into the livers of 66 streptozotocin-induced diabetic rats. In contrast to high-number islet transplantation, which restored normoglycemia in 25 control animals, the low-number islet transplantation was followed by persisting hyperglycemia for at least 13 months. Hyperplasia of islet cells developed in the transplanted islets as a consequence of hyperglycemia, which for the beta cells is not only a secretory but also a proliferative stimulus. Six of thirty-three animals between the 18th and the 24th month after islet transplantation changed from hyperglycemia to severe hypoglycemia, due to insulinomas that had developed in the liver from the transplanted islets. In contrast to other animal models, insulinoma development in this new model does not result from DNA damage by chemicals or radiation or from the expression of transgenes, but starts from apparently normal islets prepared from untreated isologous donors, which are exposed to an imbalance in glucose metabolism. The persistent proliferative stimulus and the metabolic alterations caused by the longstanding hyperglycemia seem to be the most relevant oncogenic factors in this model.


LncRNA BCAR4 promotes proliferation, invasion and metastasis of non-small cell lung cancer cells by affecting epithelial-mesenchymal transition.
Long non-coding RNAs (lncRNAs) play an important role in various cellular biological processes. It is also involved in the occurrence and development of the tumor. BCAR4 is reported to be highly expressed in breast cancer and promotes cell proliferation. However, the biological effects of BCAR4 in non-small cell lung cancer (NSCLC) remains unclear. qRT-PCR was performed for detecting BCAR4 expression in 76 pairs of NSCLC tissues and corresponding cancer-adjacent tissues and 6 NSCLC cell lines. BCAR4 expression was knocked down, and its effects on NSCLC cell proliferation, cycle, apoptosis, invasion and metastasis were studied via MTT, clone formation, flow cytometry, TUNEL and Transwell assay. Metastatic tumor model of nude mice was established to investigate its effects on NSCLC cell metastasis. BCAR4 downstream target gene protein expression was detected using Western blotting and immunofluorescence assay. BCAR4 was higher in NSCLC tissues than that in cancer-adjacent tissues and was positively correlated with tumor size, clinical stage, and distant metastasis, suggesting that BCAR4 can be used as an independent predictor of prognosis. Results also showed that BCAR4 knockdown could inhibit tumor cell invasion, metastasis, and proliferation, induce cell cycle arrest and increase cell apoptosis. BCAR4 knockdown inhibits the metastasis and invasion of tumor cells via regulating Vimentin, N-cadherin and E-cadherin in Epithelial-Mesenchymal Transition (EMT). BCAR4 promotes the invasion and metastasis of NSCLC via regulating EMT and BCAR4/EMT interaction can be used as a new target for the diagnosis and therapeutics of NSCLC.


American Association for the Surgery of Trauma Organ Injury Scaling: 50th anniversary review article of the Journal of Trauma.
The purpose of a scaling system for specific injuries is to provide a common language to facilitate the clinical decisions and the investigative basis for this decision making. This brief overview describes the evolution of the Organ Injury Scaling (OIS) system developed by the American Association for the Surgery of Trauma. The OIS system is based on the magnitude of anatomic disruption and is graded as 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), 5 (massive), and 6 (lethal). To date, the American Association for the Surgery of Trauma OIS system has been developed for visceral and vascular injuries of the neck, chest, abdomen, and extremities. The fundamental objective of OIS is to provide a common language to describe specific organ injuries. The primary purpose of OIS is to facilitate clinical decision making and the necessary research endeavors to improve this process. A good example of this concept is the tumor, node, metastasis classification for solid organ malignancies: a system used worldwide to guide patient care and clinical investigation.


Design and characterization of novel recombinant listeriolysin O-protamine fusion proteins for enhanced gene delivery.
To improve the efficiency of gene delivery for effective gene therapy, it is essential that the vector carries functional components that can promote overcoming barriers in various steps leading to the transport of DNA from extracellular to ultimately nuclear compartment. In this study, we designed genetically engineered fusion proteins as a platform to incorporate multiple functionalities in one chimeric protein. Prototypes of such a chimera tested here contain two domains: one that binds to DNA; the other that can facilitate endosomal escape of DNA. The fusion proteins are composed of listeriolysin O (LLO), the endosomolytic pore-forming protein from Listeria monocytogenes, and a 22 amino acid sequence of the DNA-condensing polypeptide protamine (PN), singly or as a pair: LLO-PN and LLO-PNPN. We demonstrate dramatic enhancement of the gene delivery efficiency of protamine-condensed DNA upon incorporation of a small amount of LLO-PN fusion protein and further improvement with LLO-PNPN in vitro using cultured cells. Additionally, the association of anionic liposomes with cationic LLO-PNPN/protamine/DNA complexes, yielding a net negative surface charge, resulted in better in vitro transfection efficiency in the presence of serum. An initial, small set of data in mice indicated that the observed enhancement in gene expression could also be applicable to in vivo gene delivery. This study suggests that incorporation of a recombinant fusion protein with multiple functional components, such as LLO-protamine fusion protein, in a nonviral vector is a promising strategy for various nonviral gene delivery systems.


Studies of natural population variability of parainfluenza viruses during their epidemic circulation.
The population of circulating serotype 3 parainfluenza virus strains isolated in different years proved to be sufficiently polymorphic concerning its antigenic and biological features as well as their virulence for newborn hamsters. The highly virulent strain population appeared to have an antigenic pattern different from that of the prototype strain. The epidemic caused by it in groups of school and preschool children was more intensive as compared to that induced by avirulent strains population.


Detection of M. tuberculosis in clinical samples of diversified nature by IS6110 based PCR.
Performance of the polymerase chain reaction technique based on IS6110 sequence was evaluated in clinical samples obtained from pulmonary and extrapulmonary cases of tuberculosis. One hundred and seventy two samples were processed for detection of M. tuberculosis by ZN stained smear examination, LJ medium culture, BACTEC radiometric culture and PCR tests amplifying 123bp region of IS6110 sequence. A significant difference was seen in the sensitivities of different tests, the figures being 83% for PCR test, 35.2% for smear examination, 47.16% for LJ culture and 53.45% for BACTEC culture (p < 0.05). However, no significant difference was found as far as specificity was concerned. PCR test sensitivity in. pulmonary and extrapulmonary clinical samples were 90.14% and 77.27% respectively and found to be significantly higher (p < 0.05) when compared with those of other tests. The mean detection time for M. tuberculosis was 24.03 days by LJ medium culture, 12.89 days by BACTEC culture and less than one day by PCR test. PCR based on IS6100 sequence is highly sensitive method for the early diagnosis of pulmonary and extrapulmonary tuberculosis.


Potentiating effect of amphotericin B on five platinum anticancer drugs in human cis-diamminedichloroplatinum (II) sensitive and resistant ovarian carcinoma cells.
We have determined an effect of amphotericin B (AMB), an antifungal drug, on the cytotoxicity of cis-diamminedichloro-platinum (II) (CDDP) and 4 CDDP analogues in a human ovarian carcinoma cell line (NOS2). Intracellular accumulation of CDDP was elevated significantly by treatment with AMB, and AMB significantly potentiated the cytotoxicity of CDDP by MTT assay. Intracellular accumulation of 4 CDDP analogues was also elevated by the treatment with AMB and the order of increasing accumulation rate of platinum drugs was consistent with that of dose modification factor (DMF). AMB also increased the intracellular CDDP accumulation in CDDP resistant cells (NOS2CR), derived from NOS2. The intracellular accumulations of 4 CDDP analogues were elevated slightly by the treatment with AMB in NOS2CR cells. DMFs of 5 platinum drugs in NOS2CR cells, however, were more than those in NOS2 cells. These results indicate that AMB sensitizes NOS2 and NOS2CR cells to platinum drugs, partially due to the increasing intracellular accumulation of these drugs. In addition, CDDP analogues are more effective in NOS2CR cells than CDDP, but the cytotoxicity of CDDP was most potentiated by AMB among the 5 platinum drugs under study.


Diabetes with obesity--Is there an ideal diet?
For individuals who are overweight or obese, weight loss is effective in preventing and improving the management of type 2 diabetes. Together with other lifestyle factors like exercise and behavior modification, diet plays a central role in achieving weight loss. Diets vary based on the type and amount of carbohydrate, fat, and protein consumed to meet daily caloric intake goals. A number of popular diets are reviewed as well as studies evaluating the effect of various diets on weight loss, diabetes, and cardiovascular risk factors. Current trends favor the low-carbohydrate, low-glycemic index, Mediterranean, and very-low-calorie diets. However, no optimal dietary strategy exists for patients with obesity and diabetes, and more research is needed. Given the wide range of dietary choices, the best diet is one that achieves the best adherence based on the patient's dietary preferences, energy needs, and health status.


Skin and soft tissue infection.
Abstract. Normal skin is heavily colonized by bacterial flora. The most common are the various nonpathogenic gram-positive bacteria such as Staphylococcus epidermidis (coagulase-negative). Skin and soft tissue infections are usually caused by Staphylococcus aureus (S. aureus) and Streptococcus pyogenes. This article discusses common and some not so common bacterial skin infections, including impetigo, folliculitis, furncles and carbuncles, cellulitis and erysipelas, gangrenous cellulitis, staphylococcal scalded skin syndrome and scarlet fever. Impetigo and ecthyma are common bacterial infections of the skin commonly caused by S. aureus and / or Group A streptoccus. In mild and localized impetigo topical antibiotics whereas in widespread or severe one and in ecthyma systemic antibiotics like, cloxacillin, erythromycin, azithromycin or cephalexin should be used. Folliculitis, furunculosis and carbuncle are folliculocentric infections caused by S. aureus involving the variable depth and extent of the follicle(s) and surrounding tissue. These conditions can be treated with topical or systemic antibiotics like cloxacillin, cephalexin, erythromycin, amoxicillin/clavulanic acid or vancomycin. Staphylococcal scalded skin syndrome is a toxin mediated exfoliative dermatosis caused by S. aureus of phase group II. Intravenous penicillinase-resistant anti-staphylococcal antibiotics like methicillin, cloxacillin, cephalosporin or erythromycin are required. Erysipelas and cellulitis are acute infections of dermal and subcutaneous tissues caused most frequently by Group A beta-hemolytic streptococci (erysipelas) or S. aureus requiring systemic antibiotics like oral or intravenous penicillin, erythromycin, cephalexin, cloxacillin, vacomycin, minocycline or ciprofloxacin depending upon the severity, suspected causative organism and culture/sensitivity results. Gangrenous cellulitis is characterized by infection with necrosis of skin and underlying subcutaneous tissue due to various pathogens occurring at different site. Ampicillin, gentamicin, and either metronidazole or clindamycin intravenously in standard doses are recommended for the treatment.


Draft genome sequencing of the sugarcane hybrid SP80-3280.
Sugarcane commercial cultivar SP80-3280 has been used as a model for genomic analyses in Brazil. Here we present a draft genome sequence employing Illumina TruSeq Synthetic Long reads. The dataset is available from NCBI BioProject with accession PRJNA272769.


In Situ Analysis of Growth Behaviors of Cu2O Nanocubes in Liquid Cell Transmission Electron Microscopy.
Metal oxides have attracted substantial attention over the years and are commonly used in the semiconductor industry because of their excellent physical and chemical properties. Among the various metal oxides, cuprous oxide (Cu2O) is regarded as a promising material. It is inexpensive, earth-abundant, and nontoxic; therefore, it can be used in catalysis, sensors, solar cells, and p-type semiconductors. However, the redox reaction of Cu2O is still uncertain. The size, morphology, and structure of Cu2O strongly influence its properties. In this work, we developed a new synthesis method of Cu2O that involves reducing the precursor by an electron beam without reducing agent. The growth process of Cu2O nanocubes was observed via in situ liquid cell transmission electron microscopy (in situ LCTEM). The nucleation kinetics, oscillating growth behavior, and redox reaction of the Cu2O nanocubes in the liquid phase were systematically studied. Cu2O exhibited a round shape at the beginning and transformed into a cubic shape afterward. Interestingly, the Cu2O nanocubes grew clearly under long-term observation; however, their diameters increased and fluctuated during the short-term observation. The electron beam not only stimulated the solution to reduce the nanocubes but also caused electron radiation effect to the nanocubes. During the Cu2O growth and dissolution, the cubic shape evolved with specific planes in the {100} family. Our direct observation sheds light on the preparation of Cu2O by a reduction method, extending the study of reaction kinetics and providing a new way to synthesize metal oxides.


Penetration of E. coli and F2 bacteriophage into fish tissues.
Throughout the world, fish thrive in rivers, lakes and seawater polluted with wastewater. Furthermore, in some countries, wastewater-enriched fishponds are used for fish cultivation. One of the major constraints in using wastewater for aquaculture is the possible contamination of the fish by enteric pathogens (bacteria and viruses), which may penetrate and accumulate in fish tissue, and constitute a potential public health hazard, especially in countries in which raw fish are consumed. In order to evaluate the infection of fish cultivated in wastewater, controlled experiments were performed to study the penetration of bacteria and bacteriophage inoculated into water tanks in which the fish were maintained. Twenty to thirty Tilapia hybrids (Sarotherodon aureus x S. niloticus), of 100 gr average weight and some 20 cm long were introduced into a 1 m3 plastic tank, containing about 500 l tap water at a temperature of 20 degrees C. High protein fish feed was added at a rate of about 1% of body weight per day. Four experiments were performed using an inoculum of an E. coli strain resistant to streptomycin and nalidixic acid. One hour after inoculation, bacterial concentration was 10(5)-10(6)/ml tank water. Four experiments were carried out with F2 male-specific bacteriophage 10(3)-10(5)/ml tank water. In each experiment two fish were sacrificed at zero time (prior to introduction of inocula), and 1, 5, 24, 48 and 72 or more hours after inoculation. Water samples were withdrawn at the same intervals. The level of microorganisms was tested in the following tissues: digestive tract, skin, spleen, liver and muscle. E. coli assays were performed using the membrane filtration technique; phages were assayed, using E. coli host cells in a plaque assay. The results of the experiments indicate that notwithstanding the high E. coli concentration in the tank water, its level in the edible tissue (muscle) was low, and in no instance higher than the acceptable standard of 400 cfu/gr (International Commission for Food Specification, 1974). The maximum concentration of F2 phage detected in muscle tissue was 350 pfu/gr. There is no standard for virus concentration in edible tissue.


Sequential DEXAS: a method for obtaining DNA sequences from genomic DNA and blood in one reaction.
Sequential DEXAS (direct exponential amplification and sequencing), a one step amplification and sequencing procedure that allows accurate, inexpensive and rapid DNA sequence determination directly from genomic DNA, is described. This method relies on the simultaneous use of two DNA polymerases that differ both in their ability to incorporate dideoxynucleotides and in the time at which they are activated during the reaction. One enzyme, which incorporates deoxynucleotides and performs amplification of the target DNA sequence, is supplied in an active state whereas the other enzyme, which incorporates dideoxynucleotides and performs the sequencing reaction, is supplied in an inactive state but becomes activated by a temperature step during the thermocycling. Thus, in the initial stage of the reaction, target amplification occurs, while in the second stage the sequencing reaction takes place. We show that Sequential DEXAS yields high quality sequencing results directly from genomic DNA as well as directly from human blood without any prior isolation or purification of DNA.


Universal interface width distributions at the depinning threshold.
We compute the probability distribution of the interface width at the depinning threshold, using recent powerful algorithms. It confirms the universality classes found previously. In all cases, the distribution is surprisingly well approximated by a generalized Gaussian theory of independent modes which decay with a characteristic propagator G(q)=1/q(d+2zeta); zeta, the roughness exponent, is computed independently. A functional renormalization analysis explains this result and allows one to compute the small deviations, i.e., a universal kurtosis ratio, in agreement with numerics. We stress the importance of the Gaussian theory to interpret numerical data and experiments.


High systemic IL-6 is associated with worse prognosis in patients with non-small cell lung cancer.
Characteristic cytokine patterns have been described in different cancer patients and they are related to their diagnosis, prognosis, prediction of treatment responses and survival. A panel of cytokines was evaluated in the plasma of non-small cell lung cancer (NSCLC) patients and healthy controls to investigate their profile and relationship with clinical characteristics and overall survival. The case-controlled cross-sectional study design recruited 77 patients with confirmed diagnosis of NSCLC (cases) and 91 healthy subjects (controls) aimed to examine peripheral pro-inflammatory and anti-inflammatory cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, TNF and IFN-γ) by Cytometry Beads Arrays (CBA Flex) in. The cytokine IL-6 showed a statistically significant difference among groups with increased expression in the case group (p < 0.001). The correlation between the cytokines expression with patient's clinical characteristics variables revealed the cytokine IL-6 was found to be associated with gender, showing higher levels in male (p = 0.036), whereas IL-17A levels were associated with TNM stage, being higher in III-IV stages (p = 0.044). We observed worse overall survival for individuals with high levels of IL-6 when compared to those with low levels of this cytokine in 6, 12 and 24 months. Further studies of IL-6 levels in independent cohort could clarify the real role of IL-6 as an independent marker of prognostic of NSCLC.