Novel image analysis approach quantifies morphological characteristics of 3D breast culture acini with varying metastatic potentials.
Prognosis of breast cancer is primarily predicted by the histological grading of the tumor, where pathologists manually evaluate microscopic characteristics of the tissue. This labor intensive process suffers from intra- and inter-observer variations; thus, computer-aided systems that accomplish this assessment automatically are in high demand. We address this by developing an image analysis framework for the automated grading of breast cancer in in vitro three-dimensional breast epithelial acini through the characterization of acinar structure morphology. A set of statistically significant features for the characterization of acini morphology are exploited for the automated grading of six (MCF10 series) cell line cultures mimicking three grades of breast cancer along the metastatic cascade. In addition to capturing both expected and visually differentiable changes, we quantify subtle differences that pose a challenge to assess through microscopic inspection. Our method achieves 89.0% accuracy in grading the acinar structures as nonmalignant, noninvasive carcinoma, and invasive carcinoma grades. We further demonstrate that the proposed methodology can be successfully applied for the grading of in vivo tissue samples albeit with additional constraints. These results indicate that the proposed features can be used to describe the relationship between the acini morphology and cellular function along the metastatic cascade.


[Impact of alcohol abuse on the composition of serum lipids in patients with tonsillitis].
The purpose of the study was to assess the impact of alcohol abuse on the composition of serum lipids in patients with tonsillitis. The values of the serum lipid spectrum were studied in 100 alcohol abusers with Streptococcus-induced lacunar tonsillitis, 100 alcoholics without markers of viral hepatitis, and 50 healthy individuals. The effect of alcohol was shown in elevated triglyceride levels in patients with alcoholism and tonsillitis. Exposed to bacterial infection, the tonsillitis patients who abused alcohol had higher levels of phospholipids and free cholesterol and lower concentrations of free fatty acids and cholesterol esters than the alcoholics. The tonsillitis patients who abused alcohol were observed to have more considerable changes in the spectrum of phospholipids as a low relative content of lysophospholipids and higher levels of phosphatidylcholine and phosphatidylethanolamine than the alcoholics, which may be due to the predominant impact of bacterial infection.


Adaptive boundaryless finite-difference method.
The boundaryless beam propagation method uses a mapping function to transform the infinite real space into a finite-size computational domain [Opt. Lett.21, 4 (1996)]. This leads to a bounded field that avoids the artificial reflections produced by the computational window. However, the method suffers from frequency aliasing problems, limiting the physical region to be sampled. We propose an adaptive boundaryless method that concentrates the higher density of sampling points in the region of interest. The method is implemented in Cartesian and cylindrical coordinate systems. It keeps the same advantages of the original method but increases accuracy and is not affected by frequency aliasing.


Mutually independent effects of adrenocorticotropin on luteinizing hormone and testosterone secretion.
In this study, we examined the effect of ACTH on the sensitivity of the testes to gonadotropin and determined the role of the testosterone (T) negative feedback system in mediating the inhibitory effect of ACTH on LH secretion in adult male rats. ACTH infusion for 3 days reduced basal levels of serum T and the T response to GnRH, but did not alter basal levels of serum LH (immunoreactive) or the LH response to GnRH. These effects required the presence of the adrenal glands. Infusion of corticosterone (B) at a dose that increased serum B concentrations 9-fold had an effect similar to that of ACTH on basal serum T levels and the serum T response to GnRH. Basal levels of serum LH and the serum LH response to GnRH were not affected by B administration. These data suggest that ACTH administration reduces the sensitivity of the testes to LH, resulting in a lower basal level of T and a reduced T response to GnRH. This effect was independent of basal serum LH levels or the LH response to GnRH. It appears that B mediates the effect of ACTH on testicular sensitivity to gonadotropin. In another experiment, ACTH administration for 4 days did not alter serum LH values, but reduced serum T levels in sham-castrated male rats. In contrast, ACTH treatment blunted the increase in serum LH after castration by day 2 of treatment, despite the absence of detectable levels of serum T within 6 h after castration. These data suggest that T is not essential for the inhibitory effect of ACTH on LH secretion to occur. They do not support the hypothesis that ACTH enhances the sensitivity of the hypothalamus and/or pituitary to the negative feedback effects of T.


[Is it already '5 past 12'?--Development of a scale for "ecological hopelessness"].
The article reports results from a second follow-up survey (N = 541) on existential anxieties with a sample from the Federal Republic of Germany in 1992 who had first been questionned in 1985 when their ages were between 8 and 20 years. The report focuses on data gathered with a new scale on 'ecological hopelessness'. The new scale is comprised of 10 items and shows high reliability. The results reveal that every third youth in the sample articulates ecological hopelessness. Analyses of variance show that there is a strong gender difference: Girls/women express more hopelessness than boys/men, correlations and regression analyses show a negative relation between hopelessness and mental health and a positive relation between hopelessness and attempted coping. It is probable that hopelessness will expand if environmental destruction becomes more intensive. Thus, psychology as a part of humanities is obliged to not only point to the dangerous consequences of hopeless per se, but also to engage in the prevention of ecological hopelessness.


Electron cryomicroscopy structure of a membrane-anchored mitochondrial AAA protease.
FtsH-related AAA proteases are conserved membrane-anchored, ATP-dependent molecular machines, which mediate the processing and turnover of soluble and membrane-embedded proteins in eubacteria, mitochondria, and chloroplasts. Homo- and hetero-oligomeric proteolytic complexes exist, which are composed of homologous subunits harboring an ATPase domain of the AAA family and an H41 metallopeptidase domain. Mutations in subunits of mitochondrial m-AAA proteases have been associated with different neurodegenerative disorders in human, raising questions on the functional differences between homo- and hetero-oligomeric AAA proteases. Here, we have analyzed the hetero-oligomeric yeast m-AAA protease composed of homologous Yta10 and Yta12 subunits. We combined genetic and structural approaches to define the molecular determinants for oligomer assembly and to assess functional similarities between Yta10 and Yta12. We demonstrate that replacement of only two amino acid residues within the metallopeptidase domain of Yta12 allows its assembly into homo-oligomeric complexes. To provide a molecular explanation, we determined the 12 Å resolution structure of the intact yeast m-AAA protease with its transmembrane domains by electron cryomicroscopy (cryo-EM) and atomic structure fitting. The full-length m-AAA protease has a bipartite structure and is a hexamer in solution. We found that residues in Yta12, which facilitate homo-oligomerization when mutated, are located at the interface between neighboring protomers in the hexamer ring. Notably, the transmembrane and intermembrane space domains are separated from the main body, creating a passage on the matrix side, which is wide enough to accommodate unfolded but not folded polypeptides. These results suggest a mechanism regarding how proteins are recognized and degraded by m-AAA proteases.


Duloxetine in the treatment of generalized anxiety disorder.
Duloxetine is a serotonin-norepinephrine reuptake inhibitor (SNRI) which is FDA approved for the treatment of generalized anxiety disorder (GAD) in doses of 30 mg to 120 mg daily. Duloxetine has been shown to significantly improve symptoms of GAD as measured through the Hamilton Anxiety Rating Scale (HAMA), the Clinical Global Impressions Scale (CGI-I), and other various outcome measures in several placebo-controlled, randomized, double blind, multi-center studies. Symptom improvement began within the first few weeks, and continued for the duration of the studies. In addition, duloxetine has also been shown to improve outcomes in elderly patients with GAD, and in GAD patients with clinically significant pain symptoms. Duloxetine was noninferior compared with venlafaxine XR. Duloxetine was found to have a good tolerability profile which was predictable and similar to another SNRI, venlafaxine. Adverse events (AEs) such as nausea, constipation, dry mouth, and insomnia were mild and transient, and occurred at relatively low rates. It was found to have a low frequency of drug interactions. In conclusion, duloxetine, a selective inhibitor for the serotonin and norepinephrine transporters, is efficacious in the treatment of GAD, and has a predictable tolerability profile, with AEs generally being mild to moderate.


1987 Kreshover lecture. Gene regulation in the development of oral tissues.
The regulatory processes associated with tooth formation are being investigated by the identification of when, where, and how cell adhesion molecules (CAMs), substrate adhesion molecules (SAMs), dentin phosphoprotein, enamel gene products, and intermediate cementum products are expressed during sequential developmental stages of morphogenesis, cytodifferentiation, dentin, enamel and cementum extracellular matrix (ECM) formation, and biomineralization. Instructive and permissive signaling is required for both morphogenesis and cytodifferentiation based upon in vitro organotypic culture studies in serumless, chemically-defined medium. Intrinsic developmental instructions, independent of exogenous growth factors, mediate tooth morphogenesis from the initiation of the dental lamina through crown and initial root development. Recent progress using recombinant DNA methods has advanced descriptions of several dental structural genes. The complete nucleic acid sequence for mouse amelogenin has been defined. This sequence is located on the mouse X chromosome and on the human X and Y chromosomes. This discussion summarizes recent results using experimental embryology, recombinant DNA technology, and immunocytology in the context of instructive epithelial-mesenchymal interactions associated with epithelial differentiation into ameloblasts, ectomesenchyme differentiation into odontoblasts, and dentin and enamel ECM biomineralization. The tooth organ provides opportunities at several levels of biological organization to investigate cellular, molecular, and developmental processes.


Gene polymorphisms, tobacco exposure and oral cancer susceptibility: a study from Gujarat, West India.
Polymorphic variability in the enzymes involved in biotransformation of tobacco-related pro-carcinogens plays an important role in modulating oral cancer susceptibility. CYP1A1*2A, CYP1A1*2C, GSTM1 and GSTT1 polymorphisms were determined in 122 oral carcinoma cases and 127 controls from Gujarat, West India using PCR-based methods. The results revealed that the polymorphic variants of CYP1A1 gene did not show association towards oral cancer risk. The GSTM1 and GSTT1 null genotypes were found to be over-represented in patients than controls, suggesting a moderate increase in risk of oral cancer. The oral cancer risk was significantly increased in the patients having either alone or concurrent deletion of GSTM1 and GSTT1. The results also suggested significant association between tobacco habits, especially chewing, variant genotypes of CYP1A1, GSTM1 and GSTT1 and oral cancer risk. Our data have provided evidence that GST polymorphism modified the susceptibility to oral cancer and individuals with variant genotypes of the three genes with tobacco habits are at significant risk of developing oral cancer.


Treatment Outcomes in CML Patients Treated With Tyrosine Kinase Inhibitors at a Tertiary Teaching Hospital in South Africa.
Chronic myeloid leukemia (CML) has become one of the most treatable hematologic neoplasms since the advent of the tyrosine kinase inhibitors (TKIs), but it was not known if similar treatment outcomes could be achieved in a resource-limited country. We tested the hypothesis that, despite challenges to access to second-generation TKIs, excellent responses could be replicated in the setting of limited resources. Records of 58 patients with newly diagnosed CML in the chronic phase treated with TKIs at a tertiary teaching hospital in Cape Town, South Africa between 2003 and 2012 were reviewed and assessed according to European LeukemiaNet (ELN) criteria. After a median follow-up of 60.5 months, progression-free survival at 60 and 96 months was 79.98% and 68.4%, respectively. Overall survival at 60 and 96 months was 92.9% and 83.6%, respectively. Progression to blast phase at 60 months was associated with poorer survival (P = .0002) but progression to accelerated phase was not (P = .1456). Attainment of a complete cytogenetic response at 12 months (P = .28) or major molecular response at 18 months (P = .268) did not have prognostic significance. Despite delays in achievement of the target responses defined according to ELN criteria, the use of imatinib mesylate as a first-line treatment can still result in treatment outcomes comparable with those in developed countries. These data suggest opportunities for improvement and success might be even greater with uninterrupted access to second-generation or newer TKIs.


Evaluating a Conditional Cash Transfer Scheme in a Maternal Health Care Utilization Program Among Rural Pregnant Women in Mysore District, India.
Background: According to the World Bank report in 2015, the maternal death rate in India was 174 per 100,000, which is among the highest in the world. The Indian Government launched the Janani Suraksha Yojana (JSY) conditional cash transfer program in 2005 to curb the adverse birth outcomes by promoting institutional delivery and providing antenatal care (ANC) services for pregnant women. This study evaluates the factors associated with JSY conditional cash transfer program in rural Mysore, India. Methods: Between 2011 and 2014, a prospective cohort study was conducted to examine the feasibility and acceptability of integrated ANC and HIV testing using mobile clinics in rural Mysore. Pregnant women in the Mysore Taluk provided an informed consent and answered an interviewer-administered questionnaire in local language, Kannada. All women underwent routine ANC services and were followed-up immediately after delivery, and 6 months and 12 months after delivery. Binary logistic regression was performed to identify factors associated with JSY benefits. Results: The mean age of the 1,806 mothers was 21.2 ± 2.2 years and 58.9% of the mothers had primary education. Nearly half (51.6%) of the women reported having received JSY benefits. Factors associated with receiving JSY benefits included pregnant woman's partner not having any formal education (adjusted odds ratio [AOR]: 1.35; 95% confidence interval [CI]: 1.01-1.80), having income ≤4,000 Indian Rupees (AOR: 1.47; 95% CI: 1.04-2.09), rare visits (once in 3 months visit) with Accredited Social Health Activists (AOR: 3.55; 95% CI: 1.55-8.51), and delivery in a public institution (AOR: 1.23; 95% CI: 1.01-1.51). Conclusions: While JSY has been operational in India since 2005, there continue to remain major gaps in the receipt of JSY services in rural India. Future interventions should include targeted services and expansion of JSY scheme, specifically among rural pregnant women, who are most at need of these services.


Effects of testosterone on the development of endometrial tumors in female rats.
Long-term treatment of mature virgin female rats with a high dose of testosterone (24 weeks at a total dose of 300 mg) was associated with the development of endometrial adenomatous hyperplasia and resulted in a high incidence of adenocarcinoma when administered in combination with 7,12-dimethyl-benz[a]anthracene (DMBA; 2 mg in 0.1 ml sesame oil) introduced into the uterine cavity. Adenomatous hyperplasia occurred in all testosterone-treated rats, both with and without ovaries. Testosterone may promote the induction of endometrial tumors by DMBA.


Detailed study of silver metallic film diffusion in a soda-lime glass substrate for optical waveguide fabrication.
We present the study of multimode glass waveguides fabricated by a silver-ion electromigration process followed by a diffusion process. The study is concerned mainly with the diffusion process, which occurs by variation of the diffusion time. The obtained guides are analyzed by the prism-coupling technique, which determines their effective refractive indices that are treated by the inverse WKB method,assumed to be proportional to the silver ions' concentration profiles, for which a Gaussian model is attributed. Diffusion coefficients then are determined from these Gaussian profiles experimentally by both methods. These diffusion coefficients show a concentration dependence related to the variation of the diffusion time. A mathematical model representing the best fit to this dependence is also presented. Finally, our results are compared with other research results, with which we find good agreement.


LACTATE DEHYDROGENASE IN TESTIS: DISSOCIATION AND RECOMBINATION OF SUBUNITS.
Electrophoretic resolution of lactate dehydrogenase in mature testes from a variety of animals revealed one or more unusual isozymes in addition to the usual five forms. Dissociation of the enzyme and recombination of the polypeptide subunits led to the formation of new isozymes and to a redistribution of activity among those normally present, indicating that lactate dehydrogenase synthesis in postpubertal testis is controlled by more than two genes.


Inoculation experiments with Bordetella bronchiseptica strains in SPF pigs.
The progeny of 9 SPF gilts fed a balanced ration (Table I) was used in an inoculation experiment with field strains of Bordetella bronchiseptica isolated in herds suffering atrophic rhinitis. Acute rhinitis was produced within a week after intranasal inoculation of B. bronchiseptica into 1 to 11-day-old piglets. Coughing occurred in some of the exposed pigs, but signs of pneumonia did not develop. A few pigs were killed at intervals of 1 to 3 weeks after exposure. These pigs all showed histological lesions in the turbinate and B. bronchiseptica was recovered from various parts of the respiratory tract. Pigs killed 3 weeks after inoculation showed advanced turbinate atrophy (Tables II and III). Among inoculated litter mates reared to slaughter weight, only one developed clinical signs (slight) of atrophic rhinitis, and a tendency towards an elimination of the B. bronchiseptica infection from the accessible part of the nasal cavity was noticed during the growth period. By examination of nasal swabs collected when the pigs were 10 to 13 weeks old, Mycoplasma flocculare was isolated as well from pigs inoculated with B. bronchiseptica as from the control pigs. The growth rate of the experimental pigs was high and no difference in feed consumption or feed conversion occurred between the exposed pigs and the control pigs. By post mortem examination of the snouts from the pigs slaughtered at approx. 85 kg live weight, severe atrophic rhinitis was not found. Approximately one third (32%) of the exposed pigs showed slight atrophic rhinitis lesions (Table IV). The results are discussed and it is concluded that the isolated B. bronchiseptica strains are pathogenic in young pigs and able to induce turbinate atrophy 2 to 3 weeks after inoculation. Turbinate atrophy induced in pigs a few weeks old, may apparently restore completely or almost completely during the growth period. Under the provided experimental conditions, infection with B. bronchiseptica did not result in the development of a lasting, growth-retarding atrophic rhinitis.


Augmented endothelium-dependent contraction to angiotensin II in the SHR aorta: role of an inducible cyclooxygenase metabolite.
The purpose of this study was to investigate the mechanisms involved in the angiotensin II-induced increase in the contractile response of the hypertensive wall after prolonged incubation in the organ-bath buffer. In 5-h incubated rings, the contractile response to angiotensin II in aortic rings with endothelium from spontaneously hypertensive rats (SHRs) was markedly exaggerated in comparison to 2-h incubated rings. No such potentiation was observed in SHR rings after removal of the endothelium or in intact and denuded Wistar-Kyoto (WKY) rat rings. Aspirin and SQ29548 inhibited and cycloheximide and actinomycin D reduced the time-dependent enhanced response to angiotensin II in rings with endothelium from SHRs. In SHR rings with endothelium incubated for 2 h, the contractions caused by angiotensin II were potently inhibited by piroxicam but were unaffected by NS-398. Conversely, in rings incubated for 5 h, the hyperresponsiveness to angiotensin II was inhibited to a greater extent by NS-398 than by piroxicam. Piroxicam but not NS-398 had a further inhibitory effect on the residual angiotensin II-induced contraction in actinomycin D-treated rings incubated for 5 h. In conclusion, our study shows that long-term incubation leads to hyperresponsiveness to angiotensin II in SHR aorta with endothelium. The enhanced response is associated with the induced release of vasoconstrictor prostanoids sensitive to the inhibitory effect of NS-398, a preferential inhibitor of COX-2.


Enhancing Therapeutic Processes in Videoconferencing Psychotherapy: Interview Study of Psychologists' Technological Perspective.
The COVID-19 pandemic caused a surge in the use of telehealth platforms. Psychologists have shifted from face-to-face sessions to videoconference sessions. Therefore, essential information that is easily obtainable via in-person sessions may be missing. Consequently, therapeutic work could be compromised. This study aimed to explore the videoconference psychotherapy (VCP) experiences of psychologists around the world. Furthermore, we aimed to identify technological features that may enhance psychologists' therapeutic work through augmented VCP. In total, 17 psychologists across the world (n=7, 41% from Australia; n=1, 6% from England; n=5, 29% from Italy; n=1, 6% from Mexico; n=1, 6% from Spain; and n=2, 12% from the United States) were interviewed. We used thematic analysis to examine the data collected from a sample of 17 psychologists. We applied the Chaos Theory to interpret the system dynamics and collected details about the challenges posed by VCP. For collecting further information about the technology and processes involved, we relied on the Input-Process-Output (IPO) model. The analysis resulted in the generation of 9 themes (input themes: psychologists' attitude, trust-reinforcing features, reducing cognitive load, enhancing emotional communication, and engaging features between psychologists and patients; process themes: building and reinforcing trust, decreasing cognitive load, enhancing emotional communication, and increasing psychologist-patient engagement) and 19 subthemes. Psychologists found new strategies to deal with VCP limitations but also reported the need for more technical control to facilitate therapeutic processes. The suggested technologies (eye contact functionality, emergency call functionality, screen control functionality, interactive interface with other apps and software, and zooming in and out functionality) could enhance the presence and dynamic nature of the therapeutic relationship. Psychologists expressed a desire for enhanced control of VCP sessions. Psychologists reported a decreased sense of control within the therapeutic relationship owing to the influence of the VCP system. Great control of the VCP system could better approximate the critical elements of in-person psychotherapy (eg, observation of body language). To facilitate improved control, psychologists would like technology to implement features such as improved eye contact, better screen control, emergency call functionality, ability to zoom in and out, and an interactive interface to communicate with other apps. These results contribute to the general perception of the computer as an actual part of the VCP process. Thus, the computer plays a key role in the communication, rather than remaining as a technical medium. By adopting the IPO model in the VCP environment (VCP-IPO model), the relationship experience may help psychologists have more control in their VCP sessions.


Development of a scoring scale for predicting the risk of postoperative complications after spinal tuberculosis debridement: a retrospective cohort study of 233 patients.
This investigation established a scoring scale for predicting the incidence of postoperative complications in patients after spinal tuberculosis debridement. A total of 232 spinal tuberculosis patients who underwent debridement surgery between January 2012 to May 2020 were included in this retrospective study. The study cohort was divided into 2 groups according to the presence or absence of postoperative complications. The complications were defined as abnormal or impaired body function caused by surgical factors (such as nerve injury and internal fixation looseness) or other factors (such as chemotherapy and bed stay). Clinical characteristics include age, body mass index (BMI), diabetes mellitus, pulmonary tuberculosis, smoking history, preoperative serum albumin, preoperative C-reactive protein (CRP), Cobb angle correction, surgical approach, operation time, etc. operative blood loss was recorded and analyzed. The clinical characteristics of spinal tuberculosis patients who suffered postoperative complications were evaluated, and a scoring scale was established using logistic regression analysis. The performance of this scoring scale was prospectively validated. Out of 232 patients, a total of 188 (81.03%) suffered postoperative complications after surgery. Multivariate binary logistic regression analysis showed that diabetes mellitus [adjusted odds ratio (OR) =1.110, P=0.046], pulmonary tuberculosis (adjusted OR =1.181, P=0.002), low preoperative serum albumin (adjusted OR =0.789, P=0.005), anterior surgical approach (adjusted OR =5.934, P=0.035), and long operation time (adjusted OR =1.019, P<0.01) were independent risk factors of postoperative complications after spinal tuberculosis debridement surgery. The above independent risk factors were assigned to establish a scoring scale for predicting postoperative complications, and receiver operating characteristic (ROC) analysis showed that the optimal cut-off value for the scoring scale was 4 points. The sensitivity and specificity of the scoring scale were 60.8% and 81.8%, respectively, based on the validation set. Using the scoring scale, spinal tuberculosis patients with a score between 4 to 9 would be considered at high risk of postoperative complications, while patients with a score of 0 to 3 would likely be at low risk of developing postoperative complications.


Temperature dependent factors influencing nutrient uptake: an analysis of responses at different levels of organization.
Ion fluxes show a characteristically biochemical dependence on temperature when observed at the membrane level and over short periods after a perturbation of temperature. The primary active transport systems are enzymic and are dependent both on substrate supply and on changes in protein conformation. The hydrophobic parts of the proteins are surrounded by lipid molecules whose physical state may crucially affect conformation changes. These lipids may undergo transitions from a fluid to a gel state at temperatures occurring in the natural environment. It will be noted that the concepts developed in model systems of pure phospholipid/protein interactions cannot be very readily applied to the spatially heterogeneous assemblies of lipid molecules and transport proteins in real cell membranes. While it is obvious that ion transport rates are responsive to temperature changes in a given cell, it is difficult to explain exactly which components of the transport process become limiting. We will show that, on cooling, the membrane potential can initially be greatly disturbed when temperature is changed and that this may be related to ATP supply to H+-translocating ATPase. This affects the driving force for all other solutes. When temperature is lowered the permeability coefficients for most ions are reduced and yet it is commonly found that diffusive efflux of ions increases in the cold. We attempt to explain this paradox on the basis of driving forces and metabolic regulation of ion transport. Acclimatory changes occur on extended exposure of a cell or an organism to a reduced growth temperature. Some of these changes occur at the membrane level and relate to lipid composition and modulation of carrier activity. Others involve changes in the relative size and sometimes the morphology of the root system. We will show that these processes lessen the temperature dependence of ion transport and ensure that the intake of nutrients does not limit growth at low temperatures. These acclimatory changes are seen as part of the general process of regulation of nutrient uptake.


The effect of oxygen inhalation on oral temperature.
A study was conducted to determine the effect of oxygen inhalation by nasal cannula on oral temperatures. One hundred healthy adult subjects were randomly assigned to a control and to three experimental groups that received 2, 4, and 6 liters per minute of oxygen for 30 minutes. Oral temperatures were measured before and 30 minutes after oxygen treatment. The data analysis did not show any significant effect of the treatment. This study encourages review of the common empirical practice of changing temperature sites from the preferred oral to the less acceptable rectal or axillary sites in patients receiving oxygen inhalation treatments.


TelAP1 links telomere complexes with developmental expression site silencing in African trypanosomes.
During its life cycle, Trypanosoma brucei shuttles between a mammalian host and the tsetse fly vector. In the mammalian host, immune evasion of T. brucei bloodstream form (BSF) cells relies on antigenic variation, which includes monoallelic expression and periodic switching of variant surface glycoprotein (VSG) genes. The active VSG is transcribed from only 1 of the 15 subtelomeric expression sites (ESs). During differentiation from BSF to the insect-resident procyclic form (PCF), the active ES is transcriptionally silenced. We used mass spectrometry-based interactomics to determine the composition of telomere protein complexes in T. brucei BSF and PCF stages to learn more about the structure and functions of telomeres in trypanosomes. Our data suggest a different telomere complex composition in the two forms of the parasite. One of the novel telomere-associated proteins, TelAP1, forms a complex with telomeric proteins TbTRF, TbRAP1 and TbTIF2 and influences ES silencing kinetics during developmental differentiation.


[Angiotensin-(1-7) protects cardiac myocytes against high glucose-induced injury by inhibiting ClC-3 chloride channels].
To explore whether angiotensin-(1-7) [Ang-(1-7)] protects cardiac myocytes against high glucose (HG)-induced injury by inhibiting ClC-3 chloride channels. H9c2 cardiac cells were exposed to 35 mmol/L glucose for 24 h to establish a cell injury model. The cells were treated with Ang-(1-7) or the inhibitor of chloride channel (NPPB) in the presence of HG for 24 h to observe the changes in HG-induced cell injury. Cell counter kit 8 (CCK-8) assay was used to test the cell viability, and the morphological changes of the apoptotic cells were detected using Hoechst 33258 staining and fluorescent microscopy. The intracellular level of reactive oxygen species (ROS) was examined by DCFH-DA staining, SOD activity in the culture medium was measured using commercial kits, and the mitochondrial membrane potential (MMP) of the cells was tested with rodamine 123 staining. The expression level of cardiac ClC-3 chloride channels was detected with Western blotting. Exposure of H9c2 cardiac cells to 35 mmol/L glucose for 24 h markedly enhanced the expressions of cardiac ClC-3 channel protein (P<0.01). Co-treatment of the cells with 1 µmol/L Ang-(1-7) and HG for 24 h significantly attenuated HG- induced upregulation of ClC-3 channel protein expression (P<0.01). Co-treatment of the cells exposed to HG with 1 µmol/L Ang-(1-7) or 100 µmol/L NPPB for 24 h obviously ameliorated HG-induced injuries as shown by increased cell viability, enhanced SOD activity, decreased number of apoptotic cells, and reduced intracellular ROS generation and loss of MMP (P<0.01). ClC-3 channels are involved in HG-induced injury in cardiac cells. Ang-(1-7) protects cardiac cells against HG-induced injury by inhibiting ClC-3 channels.


Persistence of Pasteurella multocida in Nebraska wetlands under epizootic conditions.
Gleason Basin, a marsh located in the western part of the Rainwater Basin in Nebraska, was selected during the 1980 spring waterfowl migration as a study site to determine the presence and persistence of virulent Pasteurella multocida. Avian cholera mortality in migratory waterfowl using the Basin increased during a 2-wk period of a die-off beginning the first week of March when 2,409 carcasses were collected from the marsh. Study sites within the marsh were established for sampling water associated with and not associated with intact and scavenged carcasses. Isolations of virulent P. multocida were made from five of six study sites associated with either intact or scavenged carcasses for 3 days and from three of five non-carcass-associated study sites for 2 days. Recovery of these bacteria from this environment suggested a possible source of infection for susceptible waterfowl using the contaminated site.


Frequency-dependent associative long-term potentiation at the hippocampal mossy fiber-CA3 synapse.
The mossy fiber-CA3 synapse displays an N-methyl-D-aspartate-receptor-independent mu-opioid-receptor-dependent form of long-term potentiation (LTP) that is thought not to display cooperativity or associativity with coactive afferents. However, because mossy fiber LTP requires repetitive synaptic activity for its induction, we reevaluated cooperativity and associativity at this synapse by using trains of mossy fiber stimulation. Moderate-, but not low-, intensity trains induced mossy fiber LTP, indicating cooperativity. Low-intensity mossy fiber trains that were normally ineffective in inducing LTP could induce mossy fiber LTP when delivered in conjunction with trains delivered to commissural-CA3 afferents. Associative mossy fiber LTP also could be induced with single mossy fiber pulses when delivered with commissural trains in the presence of a mu-opioid-receptor agonist. Our findings suggest a frequency-dependent variation of Hebbian associative LTP induction that is regulated by the release of endogenous opioid peptides.


Study on the reutilization of clear fracturing flowback fluids in surfactant flooding with additives for Enhanced Oil Recovery (EOR).
An investigation was conducted to study the reutilization of clear fracturing flowback fluids composed of viscoelastic surfactants (VES) with additives in surfactant flooding, making the process more efficient and cost-effective. The clear fracturing flowback fluids were used as surfactant flooding system with the addition of α-olefin sulfonate (AOS) for enhanced oil recovery (EOR). The interfacial activity, emulsification activity and oil recovery capability of the recycling system were studied. The interfacial tension (IFT) between recycling system and oil can be reduced by 2 orders of magnitude to 10(-3) mN/m, which satisfies the basic demand of surfactant flooding. The oil can be emulsified and dispersed more easily due to the synergetic effect of VES and AOS. The oil-wet surface of quartz can be easily converted to water-wet through adsorption of surfactants (VES/AOS) on the surface. Thirteen core plug flooding tests were conducted to investigate the effects of AOS concentrations, slug sizes and slug types of the recycling system on the incremental oil recovery. The investigations prove that reclaiming clear fracturing flowback fluids after fracturing operation and reuse it in surfactant flooding might have less impact on environment and be more economical.


Investigation of morbidity, length of stay, and healthcare costs of inpatient paediatric burns.
Burn injuries are the third most common cause of death in children due to trauma. Hospitalizations related to burn injuries are common. Prolonged hospitalization associated with burn treatment can result in increased resource utilization, leading to higher costs. Thus, it is essential to investigate these areas to reduce costs. The study investigated the morbidity and length of hospital stay of paediatric burn patients, as well as calculated the social security costs of hospitalization and treatment. The retrospective observational descriptive study examined the medical records of 774 paediatric patients treated in a burn intensive care unit at a tertiary medical faculty hospital between 01 March 2019 and 31 March 2022. The invoice records of payments made by the Social Security Institution to the hospital in return for health services provided to patients were examined. The healthcare costs were calculated. A total of 57.6% of the participants were boys and 79.2% were between the ages of 1-4. About 90% of the cases involved burns with a total body surface area (TBSA) of less than 20% and a 2nd-degree burn depth. Scalding was the most common cause of burns (88.2%). Among all patients, the mortality rate was 2.1% (n = 16). The mean length of hospital stay was 10.29 ± 9.59 days. The mean cost per day was 212.02 ± 190.94 US dollars ($US), and the cost per 1% TBSA was 241.70 ± 301.32 $US. According to the causes of burn injury, the mean cost of electricity was 5000.77 ± 8101.85 $US, fire 4818.02 ± 5852.22 $US, and chemical 3285.49 ± 4503.2 $US were observed in the first 3 ranks respectively. According to this study, paediatric burn cases occur due to preventable causes, and even though the mortality rate was low, the severity of burns, TBSA%, and presence of complications caused prolonged lengths of hospital stays, which caused social security costs to rise.


Chloride-depletion effects in the calcium-deficient oxygen-evolving complex of photosystem II.
The effects of Cl-depletion in photosystem II (PS-II)-enriched membranes have been investigated by electron paramagnetic resonance (EPR) spectroscopy after removal of the 17- and 23-kDa polypeptides and depletion of Ca2+ by NaCl treatment. When the salt treatment was done in the presence of a high concentration (5 mM) of the chelator [ethylenebis(oxyethylenenitrilo)]tetraacetic acid (EGTA), a modified dark-stable multiline signal was observed from the S2 state and a 13 mT wide S3 signal could be generated by illumination at 0 degrees C as reported previously for experiments conducted under these conditions [Boussac, A., Zimmermann, J.-L., & Rutherford, A. W. (1990) FEBS Lett. 277, 69-74]. The modified S2 multiline signal was lost after a further Cl- depletion in the presence of a low EGTA concentration (50 microM). Upon Cl- reconstitution, a normal S2 multiline signal could be generated by continuous illumination at 200 K. In contrast, a lowering of the EGTA concentration (50 microM) alone, in the presence of Cl- (30 mM), had no effect on the modified S2 multiline signal. These results indicate that the modification of S2 is due to binding of the chelator to PS-II and that Cl- stabilizes the chelator binding. When Cl- depletion in Ca(2+)-depleted PS-II was done in the presence of a high concentration of EGTA (5 mM), the modified S2 multiline signal disappeared but was regenerated by Cl- reconstitution in darkness. These results indicate that when Cl- depletion is done to the EGTA-modified PS-II, the S2 multiline signal disappears but the S2 state remains stable in the dark.(ABSTRACT TRUNCATED AT 250 WORDS)


Fundamentals for Future Mobile-Health (mHealth): A Systematic Review of Mobile Phone and Web-Based Text Messaging in Mental Health.
Mobile phone text messages (short message service, SMS) are used pervasively as a form of communication. Almost 100% of the population uses text messaging worldwide and this technology is being suggested as a promising tool in psychiatry. Text messages can be sent either from a classic mobile phone or a web-based application. Reviews are needed to better understand how text messaging can be used in mental health care and other fields of medicine. The objective of the study was to review the literature regarding the use of mobile phone text messaging in mental health care. We conducted a thorough literature review of studies involving text messaging in health care management. Searches included PubMed, PsycINFO, Cochrane, Scopus, Embase and Web of Science databases on May 25, 2015. Studies reporting the use of text messaging as a tool in managing patients with mental health disorders were included. Given the heterogeneity of studies, this review was summarized using a descriptive approach. From 677 initial citations, 36 studies were included in the review. Text messaging was used in a wide range of mental health situations, notably substance abuse (31%), schizophrenia (22%), and affective disorders (17%). We identified four ways in which text messages were used: reminders (14%), information (17%), supportive messages (42%), and self-monitoring procedures (42%). Applications were sometimes combined. We report growing interest in text messaging since 2006. Text messages have been proposed as a health care tool in a wide spectrum of psychiatric disorders including substance abuse, schizophrenia, affective disorders, and suicide prevention. Most papers described pilot studies, while some randomized clinical trials (RCTs) were also reported. Overall, a positive attitude toward text messages was reported. RCTs reported improved treatment adherence and symptom surveillance. Other positive points included an increase in appointment attendance and in satisfaction with management and health care services. Insight into message content, preventative strategies, and innovative approaches derived from the mental health field may be applicable in other medical specialties.


An early postpartum hospital discharge program: implementation and evaluation.
The philosophy of the FBC strengthens the concept of childbirth as a normal physiologic process. Couples are guaranteed a high level of quality nursing and medical care. Simultaneously, provisions are made to enhance the family's assertiveness in obtaining a satisfying experience in the hospital that extends to the home environment. With careful planning and decision making throughout the pregnancy, early discharge becomes a satisfying and safe alternative for families and provides a means to decrease the ever rising cost of health care.


Removal of extracorporeal carbon dioxide in chronic obstructive pulmonary disease patients.
The use of invasive mechanical ventilation (IMV) procedures in chronic obstructive pulmonary disease (COPD) patients suffering from episodes of acute exacerbation are associated with high rates of mortality. In this case study, we describe the use of a new device for extracorporeal carbon dioxide removal (ECCO2R) that can provide partial respiratory support for patients where noninvasive ventilation (NIV) proved insufficient. The case described in this manuscript represents the first clinical feasibility study for the Hemolung device, and was also the first use and application of the device at our department.


Acute renal failure due to rifampicin (R-ARF).
Five episodes of acute renal failure due to rifampicin (R-ARF) were observed in four patients and the clinical and histological data were compared with the records of 52 episodes reported in the literature. The bulk of data supports the assumption that the by far most frequent renal injury responsible for R-ARF is acute tubular necrosis produced by a vasomotor mechanism. Nevertheless a few data, above all immunohistological findings, suggest the local presence of allergic process. It may be, that the development of an immunological renal lesion is prevented or blunted by the consequences of vasomotor effects.


In vivo safety and tolerability study of QR-441(a) using three dose formulations and three routes of administration in chickens.
The current study assessed the safety, tolerability, and palatability of the experimental drug QR-441(a) using three dose formulations and three routes of administration. A 4-day study was carried out using a total of 132 chickens. A total of 11 groups were formed (12 chickens per group) subjected to varying concentrations and routes of administration of QR-441(a). Chickens were given a high, medium, or low dose of QR-441(a) in either feed, water, or both for a period of 4 days. In addition, one group was dosed intranasally, one drop per nostril four times a day. Although no lesions were found to suggest toxicity or irritability, the medium- and high-dose water groups reduced their water intake. This reduction in water intake suggests that chickens may find the medium and high water doses unpalatable. There was no reduction in water intake in the low-dose water groups or in any of the formulated feed groups. There was also no evidence of toxicity or irritability in the nasal-dose group. These data support the use of the low, medium, and high doses in feed and the use of the low-dose concentration in water for the administration of QR-441(a). The data also suggest that QR-441(a) can be administered intranasally without the presence of any adverse events.


Nanocolloidal gold-based immunoassay for the detection of the N-methylcarbamate pesticide carbofuran.
Nanocolloidal gold particles were prepared and labeled to an anti-carbofuran monoclonal antibody (Mab). This conjugate was dispensed on the conjugated pad of a porous glass fiber. Ovalbumin (OVA)-carbofuran and goat anti-mouse IgG were dispensed on the nitrocellulose (NC) membrane and served as the test line and control line, respectively. The carbofuran-containing sample migrated to the NC membrane and reacted with the anti-carbofuran Mab labeled with the colloidal gold. The mixture diffused along the membrane and passed through the OVA-carbofuran in the test line via capillary action. The more analyte present in the sample, the more effectively it will compete with the carbofuran immobilized on the test line for binding to the limited amount of antibody labeled with colloidal gold. An adequate amount of carbofuran could prevent attachment of the colored conjugate to the test line. The presence or absence of a colored band on the test line could indicate a negative or positive result, respectively. When measured to the water sample spiked with carbofuran, this was obtained at or above 0.25 mg/L of carbofuran. The major advantages of the one-step strip test are that the detection time needed was <10 min and all of the reagents are included in the test device.


[G-CSF and GM-CSF in treatment of neutropaenia after chemotherapy in children with neoplasms].
A total number of 608 cycles of G-CSF and/or GM-CSF was applied in 280 patients aged from 6 months to 20 years during neutropaenia associated with chemotherapy of children's neoplasms (NHL-124, NBL-42, RMS-36, Nephroblastoma-18, Osteosarcoma-17, Ewing's Sarcoma-14, Hepatoblastoma-6, Neurofibrosarcoma-6, PNET-5, Medulloblastoma-3, Fibrohistiocytoma-3, Angiosarcoma-2, other - 4). G-CSF - Neupogen (Filgastrim, Hoffman La Roche - 492 cycles) and GM-CSF - Leucomax (Molgramostim, Shering Plough - 116 cycles) were administered 5 mg/kg/day s.c. Forty one children with malignancies (NHL -21 cases, solid tumours -17) treated before cytokines were in use served as a control group. Our study demonstrated that G-CSF and GM-CSF therapy, gives a shorter period of neutropaenia, reduction of the number of febrile days, decreased frequency of infection and shortened its duration.


[Pollution characteristics of carbonaceous aerosols in PM2.5 during typical winter days in Wuxi City ].
The purpose of this study was to investigate the process of haze in winter and the variation of carbonaceous aerosols in haze days. Continuous measurements of PM2.5 and meteorological parameters were conducted from Dec 3rd ,2013 to Jan 3rd, 2014, in Wuxi City. The carbonaceous component was quantified with the thermal/optical transmission (TOT) method. The results showed that: Three times of haze progresses occurred during the sampling period. Cold air, wind and rainfall were the most efficient ways to improve air quality. The mass concentration of PM2.5, OC and EC were (132.38 ± 87.17) μg.m-3, (22.80±9.77) μg.m-3 and (2.08 ± 1. 63) μg.m-3, respectively. The TC accounted for 23.57% of the PM2.5; at the same time, the TC and PM2.5 were found to be strongly correlated (correlation coefficients = 0. 730). There was a negative correlation between the ratio of carbonaceous aerosol in PM2.5 and the concentration of PM2.5, and the ratio in haze days was lower than that in normal days, which suggested that secondary inorganic particles (SO(2-)(4) , NO(-)(3), NH: ) may have a fast growth in haze days. Average OC/EC ratio was 12. 83, and there was a poor correlation between OC and EC, indicating that secondary pollutants might exist. The secondary organic carbon (SOC) was estimated to be 9.04 μg.m -3, accounting for 40. 96% of OC.


Plant Size and Competitive Dynamics along Nutrient Gradients.
Resource competition theory in plants has focused largely on resource acquisition traits that are independent of size, such as traits of individual leaves or roots or proportional allocation to different functions. However, plants also differ in maximum potential size, which could outweigh differences in module-level traits. We used a community ecosystem model called mondrian to investigate whether larger size inevitably increases competitive ability and how size interacts with nitrogen supply. Contrary to the conventional wisdom that bigger is better, we found that invader success and competitive ability are unimodal functions of maximum potential size, such that plants that are too large (or too small) are disproportionately suppressed by competition. Optimal size increases with nitrogen supply, even when plants compete for nitrogen only in a size-symmetric manner, although adding size-asymmetric competition for light does substantially increase the advantage of larger size at high nitrogen. These complex interactions of plant size and nitrogen supply lead to strong nonlinearities such that small differences in nitrogen can result in large differences in plant invasion success and the influence of competition along productivity gradients.


[The nucleus cervicalis lateralis in sheep].
The objective of the work was to determine: a) the presence of the nucleus cervicalis lateralis in the sheep, b) the extent of this nucleus in the spinal cord and medulla oblongata, and c)the number and size of its cells. The histological method of staining the nerve tissue with methylene blue according to Nissl was employed. The nucleus cervicalis lateralis of the sheep is situated in the lateral funiculus, in the caudal part of the medulla oblongata and in the first three cervical segments of the spinal cord. The total number of cells making up the studied nucleus was 1629 in sheep I, 678 in sheep II, and 732 in sheep III. The average size of the cells ranged between 18.0 and 28.0 mu. In comparison with the same nucleus examined in other animals, that of the sheep shows a number of cell-free areas. It is composed of a very small number of cells, whose average diameter is small. These characteristics make it possible to regard the nucleus cervicalis lateralis in the sheep as a rudimentary structure.


Training in normobaric hypoxia and its effects on acute mountain sickness after rapid ascent to 4559 m.
In a randomized, placebo-controlled, double-blind study, we tested a 4-week program in normobaric hypoxia that is commercially offered for the prevention of acute mountain sickness (AMS). Twenty-two male and 18 female healthy subjects [mean age 33 +/- 7 (SD) years] exercised 70 min, 3 x /week for 3 weeks on a bicycle ergometer at workloads of 60% VO2max either in normoxia (normoxia group, NG) or in normobaric hypoxia (hypoxia group, HG), corresponding to altitudes of 2500, 3000, and 3500 m during weeks 1, 2, and 3, respectively. Four passive exposures of 90 min in normoxia (NG) or hypoxia corresponding to 4500 m (HG) followed in week 4. Five days after the last session, subjects ascended within 24 h from sea level to 4559 m (one overnight stay at 3611 m) and stayed there for 24 h. AMS was defined as LL (Lake Louise score) > or =5 and AMS-C > or =0.70. The AMS incidence (70% in NG vs. 60% in HG, p = 0.74), LL scores (7.1 +/- 4.3 vs. 5.9 +/- 3.4, p = 0.34), and AMS-C scores (1.50 +/- 1.22 vs. 0.93 +/- 0.81, p = 0.25) at the study endpoint were not significantly different between the groups. However, the incidence of AMS at 3611 m (6% vs. 47%, p = 0.01) and the functional LL score at 4559 m were lower in HG. SpO2 at 3611 m, heart rate during ascents, and arterial blood gases at 4559 m were not different between groups. We conclude that the tested program does not reduce the incidence of AMS within a rapid ascent to 4559 m, but our data show that it prevents AMS at lower altitudes. Whether such a program would prevent AMS at higher altitudes, but with slower ascent, remains to be tested.


[The oncogene concept: molecular biological methods and parameters for characterizing gastrointestinal tumors].
Hitherto, research on diagnosis and therapy of cancer has been mainly of empirical nature. Besides some promising results in both fields of cancer research using traditional techniques, cell biological approaches offer a better understanding of the regulation of growth and differentiation. Immunological and, particularly, molecular biological methods contribute to this optimism. However, the use of new methods does not necessarily mean that correlation studies elucidate causal relations. Besides methodological explanations this article reviews general aspects of protooncogenes, their activation and the impact of growth factors and receptors in the multistep process of malignant development. The second part focuses on clinical applications of molecular and cellular biological analyses of gastrointestinal tumors.


Structure and function of aerotolerant, multiple-turnover THI4 thiazole synthases.
Plant and fungal THI4 thiazole synthases produce the thiamin thiazole moiety in aerobic conditions via a single-turnover suicide reaction that uses an active-site Cys residue as sulfur donor. Multiple-turnover (i.e. catalytic) THI4s lacking an active-site Cys (non-Cys THI4s) that use sulfide as sulfur donor have been biochemically characterized -- but only from archaeal methanogens that are anaerobic, O2-sensitive hyperthermophiles from sulfide-rich habitats. These THI4s prefer iron as cofactor. A survey of prokaryote genomes uncovered non-Cys THI4s in aerobic mesophiles from sulfide-poor habitats, suggesting that multiple-turnover THI4 operation is possible in aerobic, mild, low-sulfide conditions. This was confirmed by testing 23 representative non-Cys THI4s for complementation of an Escherichia coli ΔthiG thiazole auxotroph in aerobic conditions. Sixteen were clearly active, and more so when intracellular sulfide level was raised by supplying Cys, demonstrating catalytic function in the presence of O2 at mild temperatures and indicating use of sulfide or a sulfide metabolite as sulfur donor. Comparative genomic evidence linked non-Cys THI4s with proteins from families that bind, transport, or metabolize cobalt or other heavy metals. The crystal structure of the aerotolerant bacterial Thermovibrio ammonificans THI4 was determined to probe the molecular basis of aerotolerance. The structure suggested no large deviations compared with the structures of THI4s from O2-sensitive methanogens, but is consistent with an alternative catalytic metal. Together with complementation data, use of cobalt rather than iron was supported. We conclude that catalytic THI4s can indeed operate aerobically and that the metal cofactor inserted is a likely natural determinant of aerotolerance.


The second triannulenylene: tri-[8]annulenylene.
Room-temperature dehydrohalogenation of bromocyclooctatetraene (BrC8H7) with potassium tert-butoxide followed (after a couple of minutes) by alkali metal reduction was used to generate the anion radical of tri-[8]annulenylene [(C8H6*-)3] in HMPA. EPR analysis reveals that the odd electron is primarily located in one of the three eight-membered ring systems, which is rendered planar. Excellent agreement was obtained between spin densities predicted by B3LYP/6-31G* calculations and those observed. The neutral tri-[8]annulenylene system has a propensity toward polymerization, but it can be isolated for NMR and mass spectral analysis via the I2 oxidation of the anion radical. The NMR analysis reveals that two of the eight-membered rings are bent above the plane of the benzene ring and the other is bent below. Tri-[6]annulenylene (triphenylene) is the only other known member of the triannulenylenes.


Revealing the Chemical Instability of Mg3Sb2-xBix-Based Thermoelectric Materials.
n-Type Mg3Sb2-xBix alloys have been regarded as promising thermoelectric materials due to their excellent performance and low cost. For practical applications, the thermoelectric performance is not the only factor that should be taken into consideration. In addition, the chemical and thermal stabilities of the thermoelectric material are of equal importance for the module design. Previous studies reported that the Mg3Sb2-xBix alloys were unstable in an ambient environment. In this work, we found that Mg3Sb2-xBix alloys reacted with H2O and O2 at room temperature and formed amorphous Mg(OH)2/MgO and crystalline Bi/Sb. The substantial loss of Mg resulted in a significant deterioration in thermoelectric properties, accompanied by the transition from n-type to p-type. With the increase in Bi content, the chemical stability decreased due to the higher formation energy of Mg3Bi2. A chemically stable Mg3Bi2 sample was achieved by coating it with polydimethylsiloxane to isolate H2O and O2 in the air.


Age-related changes in cytokine expression by neutrophils of foals stimulated with virulent Rhodococcus equi in vitro.
Although evidence exists that neutrophils play a vital role in resistance to infection with Rhodococcus equi, the means by which neutrophils exert their effects have not been clearly defined. In the present study we evaluated differences in cytokine expression by unstimulated and R. equi-stimulated neutrophils obtained from newborn foals and subsequently at 2-, 4-, and 8-weeks of age. Stimulation with virulent R. equi induced significantly (P<0.05) greater expression of IFNgamma, TNFalpha, IL-6, IL-8, IL-12p40, IL-12p35, and IL-23p19 mRNA relative to expression by unstimulated neutrophils, and there were significant effects of age on expression of IL-6, IL-8, IL-12p40 and IL-23p19. Neutrophil expression of IL-6 and IL-8 in newborn foals was significantly greater than expression at 2-, 4-, and 8-weeks of age. Expression of IL-12p40 by R. equi-stimulated neutrophils from newborn and 2-week-old foals did not differ from that of unstimulated neutrophils; however, expression of IL-12p40 by neutrophils from 4- and 8-week-old foals was significantly greater when stimulated by R. equi than without stimulation. These results demonstrate that foal neutrophils increase mRNA expression of many pro-inflammatory cytokines, including IFNgamma, in response to in vitro stimulation with R. equi, and that the magnitude of this expression with respect to IL-6, IL-8, IL-12p40 and IL-23p19 is influenced by age. The clinical importance of the age-related difference in R. equi-induced expression of IL-12p40 to susceptibility to R. equi pneumonia remains to be determined.


Influence of dietary urea level on digestive function and growth performance of cattle fed steam-flaked barley-based finishing diets.
Four Holstein steers (282 kg) with cannulas in the rumen and proximal duodenum were used in a 4 x 4 Latin square experiment to evaluate the influence of dietary urea level (0, 0.4, 0.8, and 1.2%, DM basis) in a steam-flaked barley-based finishing diet on digestive function. There were no treatment effects (P > 0.20) on ruminal digestion of OM and ADF. Increasing dietary urea level increased (linear, P < 0.01) ruminal starch digestion. Ruminal degradability of protein in the basal diet (no supplemental urea) was 60%. Increasing dietary urea level did not increase (P > 0.20) ruminal microbial protein synthesis or nonammonia N flow to the small intestine. There were no treatment effects (P > 0.20) on total-tract ADF digestion. Total tract digestion of OM (quadratic, P < 0.01) and starch (linear, P < 0.05) increased slightly with increasing urea level. Urea supplementation increased (linear, P < 0.01) ruminal pH 1 h after feeding; however, by 3 h after feeding, ruminal pH was lower (cubic, P < 0.05) with urea-supplemented diets. Urea supplementation did not affect (P > 0.20) ruminal molar proportions of acetate and propionate. One hundred twenty crossbred steers (252 kg; approximately 25% Brahman breeding) were used in an 84-d feeding trial (five pens per treatment) to evaluate treatment effects on growth performance. Daily weight gain increased (linear, P = 0.01) with increasing urea level, tending to be maximal (1.53 kg/d; quadratic, P = 0.13) at the 0.8% level of urea supplementation. Improvements in ADG were due to treatment effects (linear, P < 0.01) on DMI. Urea supplementation did not affect (P > 0.20) the NE value of the diet for maintenance and gain. Observed dietary NE values, based on growth performance, were in close agreement with expected based on tabular values for individual feed ingredients, averaging 100.4%. We conclude that with steam-flaked barely-based finishing diets, ruminal and total-tract digestion of OM and ruminal microbial protein synthesis may not be increased by urea supplementation. In contrast, ADG was optimized by dietary inclusion of 0.8% urea. Urea supplementation may not enhance the net energy value of steam-flaked barely-based finishing diets when degradable intake protein is greater than 85% of microbial protein synthesis.


[Fibrinolytic properties and thrombolytic effect of a novel fibrinolytic enzyme from Streptomyces sp. Y405].
A novel protease (designated as SW-1) purified from the fermentation broth of Streptomyces sp. strain Y405 showed fibrinolytic activity. In vitro, on plasminogen-free fibrin plate which had been heated at 85 degrees C for 30 minutes to eliminate plasminogen, SW-1 showed the same fibrinolytic activity as the mixture of SW-1 and plasminogen. Without adding plasminogen into the fibrin clot tube SW-1 showed the same effect as with plasminogen (P > 0.05). The results might indicate that SW-1 is a fibrinolytic enzyme which degrades fibrin directly, but not a plasminogen activator which degrades fibrin by activating plasminogen. SW-1 was found also to degrade fibrinogen. In vivo, the thrombolytic effect of SW-1 (4000 u.kg-1) on venous thrombus in rat was most remarkable versus that of control(P < 0.001), but was not divergent versus that of urokinase at the some dose(P > 0.05). SW-1 was shown to enhance plasminogen and plasmin activity but did not show significant effect on endogenous t-PA or alpha 2-PI. SW-1 also caused decrease of fibrinogen level in plasma, indicating that it degrades the fibrin in thrombus and at the same time degrades the circulating fibrinogen to certain extent. The changes of these biochemical data demonstrated the thrombolytic properties of SW-1 in vivo.


Can there be a multi-bond between noble gas and metal? A theoretical study of F2XeMoF2.
A new noble gas compound containing a Xe-Mo double bond, F2XeMoF2, was theoretically constructed and studied based on DFT and ab initio calculations. The CCSD(T)-calculated Xe-Mo bond length of 2.518 Å was comparable to the standard value of 2.56 Å. The bonding energy (32.3 kcal mol-1) was even higher than that of the Xe-Au bond in the well-known XeAuF complex (24.1 kcal mol-1). The result of natural bond orbital (NBO) analysis indicates that there is a σ-bond and a π-bond between the Xe and Mo atoms in F2XeMoF2. The properties of the Xe-Mo double bond were also analyzed with the atoms in molecules (AIM) approach and natural resonance theory (NRT).


Urinary biomarkers as indicator of chronic inflammation and endothelial dysfunction in obese adolescents.
Obesity is a pro-inflammatory state that may predispose patients to acute coronary syndrome characterized by chronic low grade inflammation resulting in endothelial dysfunction (ED). The aim of the study was to evaluate urinary biomarkers of inflammation and ED in adolescents with obesity. Sixty three subjects were recruited for the study. Twenty healthy adolescents with normal body mass (NW), 14 overweight (OW), 29 obese (OA) subjects were selected. An EndoPat 2000 device was used to measure the reactive hyperemia index (RHI). First morning fasting urine samples were tested for interleukin 6 (IL-6), endothelin 1 (ET-1), alpha-1-acid glycoprotein (AGP), tumor necrosis factor- α (TNF-α) and corrected to urinary creatinine. Urinary TNF-α was significantly higher in OA group (52.4 ± 15.3 pg/mg) compared to adolescents with NW (14.1 ± 1.2 pg/mg, P = 0.04). ET-1 levels were found to be higher in OW (5.18 ± 1.6 pg/mg) compared with NW (3 · 47 ± 0.3 pg/mg, P = 0.24); and higher in OA (8.48 ± 3.1 pg/mg) compared to both NW (P = 0.19) and OW (P = 0.40). Similarly a higher AGP level was observed in OW (864.8 ± 156 ng/mg) and OA (808.3 ± 186 ng/mg) compared to NW (653 ± 69 ng/mg) (P = 0.16 & 0.49 respectively). Inflammatory markers namely, TNF-α, IL-6 and AGP significantly and positively correlated with each other and with ET-1, a marker for endothelial dysfunction. This significant correlation was also observed when tested separately in the subgroups (NW, OW and OA). There were no differences in RHI levels among the study groups. Urinary TNF-alpha is significantly elevated in obese adolescents and correlates with urinary ET-1, which is recognized as a biomarker for endothelial dysfunction. Since obesity is a chronic inflammatory state, elevated urinary TNF-alpha might be used as a non invasive tool to monitor the level of that inflammation.


Breast image registration and deformation modeling.
Image-based examination of the breast facilitates the detection of breast diseases, particularly of present benign and malignant lesions. For computer-aided processing of serial and multimodal clinical data, both for visual correlation and quantitative analysis, automated image-registration methods are an indispensable tool. The wide range of modalities and the high variability of breast appearance have led to a large diversity of proposed approaches for tissue deformation modeling and image registration. In this article, we review current developments in breast image registration techniques, and comment on their clinical relevance, individual capabilities, and open challenges.


The fragmentomic property of plasma cell-free DNA enables the non-invasive detection of diabetic nephropathy in patients with diabetes mellitus.
Diabetic nephropathy (DN) is one of the most prevalent complications of diabetes mellitus (DM). However, there is still a lack of effective methods for non-invasive diagnosis of DN in clinical practice. We aimed to explore biomarkers from plasma cell-free DNA as a surrogate of renal biopsy for the differentiation of DN patients from patients with DM. The plasma cell-free DNA (cfDNA) was sequenced from 53 healthy individuals, 53 patients with DM but without DN, and 71 patients with both DM and DN. Multidimensional features of plasma DNA were analyzed to dissect the cfDNA profile in the DM and DN patients and identify DN-specific cfDNA features. Finally, a classification model was constructed by integrating all informative cfDNA features to demonstrate the clinical utility in DN detection. In comparison with the DM patients, the DN individuals exhibited significantly increased cfDNA concentration in plasma. The cfDNA from the DN patients showed a distinct fragmentation pattern with an altered size profile and preferred motifs that start with "CC" in the cfDNA ending sites, which were associated with deoxyribonuclease 1 like 3 (DNASE1L3) expression in the kidney. Moreover, patients with DM or DN were found to carry more alterations in whole-genome cfDNA coverage when compared with healthy individuals. We integrated DN-specific cfDNA features (cfDNA concentration, size, and motif) into a classification model, which achieved an area under the receiver operating characteristic curve (AUC) of 0.928 for the differentiation of DN patients from DM patients. Our findings showed plasma cfDNA as a reliable non-invasive biomarker for differentiating DN patients from DM patients. The utility of cfDNA in clinical practice in large prospective cohorts is warranted.


[Effectiveness of sunscreen against melanoma].
Melanoma represents the fifth most common cancer in Switzerland and its incidence is rising over the past decades. A new debate is going on about the efficacy of sunscreen against the risk of developing melanoma. Few studies have proven its efficacy with a significant risk of overexposure to sunlight due to the feeling of overprotection offered by those sunscreens. The role of the physician is to explain this risk and to integrate sunscreens among a wide range of other strategies existing in primary prevention of melanoma.


Continuous hydrolysis of olive oil by immobilized lipase in organic solvent.
Lipase (EC 126.96.36.199) from Candida rugosa was immobilized with DEAE-Sephadex A50, Sephadex G50, Sephadex LH-20, Amberlite IRA94, and Amberlite XAD-7. The enzyme immobilized with DEAE-Sephadex A50 was found to be most effective for continuous hydrolysis of olive oil in isooctane. For the continuous reaction, 0.2 g of dry immobilized enzyme was swollen with predetermined amount of water, and packed in a glass column reactor. When the organic solvent (Isooctane) containing olive oil substrate was co-currently fed with aqueous buffer, the two phases were evenly distributed throughout the packed bed without surfactant supplement or prior mixing of the two phases. A small amount of the surfactant (AOT) was used only in packing procedure, and no additional surfactant was necessary thereafter. Effects of initial water content of the swollen gel, buffer types, and strength were examined in the continuous reaction. Our results suggest that the operational half-life was affected by desorption of the bound enzyme. Under the conditions of 20% olive oil in isooctane and 25 mM triethanolamine buffer (pH 7.0), operational half life was 220 h at 30 degrees C. The reactor was also operable with n-hexane, but the operational stability of the immobilized enzyme in n-hexane was only half of that in isooctane. Our results indicate that various enzyme carrier having hydrophilic or amphiphilic properties could be used for two-phase continuous reaction in packed-bed column, reactor without any surfactant supply or prior dispersion of the two immiscible phases.


The Association Between Experimentally Induced Stress, Performance Monitoring, and Response Inhibition: An Event-Related Potential (ERP) Analysis.
Psychological stress is increasingly associated with alterations in performance and affect. Yet, the relationship between experimentally induced psychological stress and neural indices of performance monitoring and error processing, as well as response inhibition, are unclear. Using scalp-recorded event-related potentials (ERPs), we tested the relationship between experimental stress, using the Trier Social Stress Test (TSST), and the error-related negativity (ERN), error positivity (Pe), and N2 ERP components. A final sample of 71 undergraduate students were randomly assigned to go through the TSST (n = 36; 18 female) or a brief mindfulness relaxation exercise (n = 35; 16 female) immediately followed by a go/no-go task while electroencephalogram (EEG) data were collected. Salivary cortisol, heart rate, and blood pressure confirmed increased physiological stress in the TSST group relative to control. Reaction times, accuracy, and post-error slowing did not differ by stress group. Two-group (TSST, control) by 2-trial type (correct, incorrect for ERN/Pe; go correct, no-go correct for N2) repeated measures ANOVAs for the ERN, Pe, and N2 showed the expected main effects of trial type; neither the ERN nor the N2 ERP components showed interactions with the stress manipulation. In contrast, the Pe component showed a significant Group by Trial interaction, with reduced Pe amplitude following the stress condition relative to control. Pe amplitude did not, however, correlate with cortisol reactivity. Findings suggest a reduction in Pe amplitude following experimental stress that may be associated with reduced error awareness or attention to errors following the TSST. Given the variability in the extant literature on the relationship between experimentally induced stress and neurophysiological reflections of performance monitoring, we provide another point of data and conclude that better understanding of moderating variables is needed followed by high-powered replication studies to get at the nuance that is not yet understood in the relationship between induced stress and performance monitoring/response inhibition processes.


Clinical trials with Alice strain, live, attenuated, serum inhibitor-resistant intranasal influenza A vaccine.
Two clinical trials with Alice strain intranasal influenza vaccine were performed. In study no. 1 (utilizing random selection and double-blind control), 50 subjects received a bivalent inactivated influenza vaccine intramuscularly, 99 subjects received Alice strain vaccine intranasally, and 50 subjects received a placebo intranasally. No symptomatology could be attributed to the intranasal route of immunization. Convalescent-phase geometric mean titers of hemagglutination inhibition antibody were higher after intramuscular vaccination; seroconversion occurred in 16 or 17 recipients of the Alice strain, with initial titers of less than 1:8. Clinical and virologic surveillance for 20 weeks after vaccination revealed no influenza A illnesses in participants of the study. In study no. 2, 75% of the subjects with initial nasal antibody titers of less than 1:3 developed measurable nasal antibody after receiving Alice strain vaccine.


Evaluation of MUC1 splice variants as prognostic markers in patients with ductal carcinoma in situ of the breast.
Despite intense research in the field of breast cancer it still remains the most common cancer in women in the Western world. A decreasing trend in mortality was mainly achieved by improved early detection which led to an increased incidence of ductal carcinoma in situ (DCIS) of the breast. For the patient's prognosis and the administration of a patient-tailored therapy strategy it is crucial to identify diagnostic and prognostic markers for high-risk DCIS patients. MUC1 is associated with tumour aggressiveness in human breast cancer. Recent studies used MUC1 splice variant A to identify malignant thyroid cancer. In the present study we have examined the usefulness of MUC1 splice variants as prognostic markers in DCIS. We used laser capture microdissection of paraffin-embedded tissue to isolate RNA from isolated tumour cells and determined the MUC1 splice variant distribution by RT-PCR. In the majority of cases variant B was more highly expressed than variant A. This was true for pure DCIS (66%) as well as for DCIS with adjacent invasive cancer (66%). In 7 out of 18 cases (38%) of pure DCIS variant A was not expressed at all. In DCIS with adjacent invasive cancer only 2 samples out of 12 showed this expression pattern (16%). The situation that variant A was more highly expressed than B, or that variant B was not expressed at all, was similar for pure DCIS (27%) and for DCIS with adjacent invasive cancer (33%). The present study describes the differences of MUC1 splice variant expression in pure DCIS compared to DCIS with adjacent invasive cancer. A discriminating pattern of MUC1 splice variants could not be demonstrated.


Pantyhose prosthesis: a cosmetic alternative.
A cosmetic prosthesis for the nonambulatory patient with unilateral or bilateral above-knee amputation is described. This device can be made with minimal cost and difficulty, and it offers advantages of durability, flexibility, and excellent appearance. Cosmetic prostheses for patients with below-knee or hip disarticulation amputations can be made in a similar manner.


Subclinical delta status in the newborn--an unfavorable prognostic sign.
A hitherto undescribed, unusual EEG abnormality invariably associated with a poor prognosis was reported and was called subclinical delta status. It consisted of continuous discharges of high voltage monomorphic or polymorphic delta activity occurring diffusely but often asynchronously in all leads, without sleep cycles. These discharges when monomorphic may be confused with respiratory artefacts, and when polymorphic they may be mistaken for part of the background activity. Four neonates with this abnormality all had intracranial bleeding and were mechanically ventilated because of frequent apneic attacks. Staring or deviation of the eyes was frequently observed during the EEG recording. A small dose of intravenous diazepam temporarily abolished this activity. Three infants died and the other survived with neurological sequelae.


In vitro selection of RNA aptamer and specific targeting of ErbB2 in breast cancer cells.
The ErbB family (also referred to as HER/neu or HER) of receptor tyrosine kinases plays major roles in the formation and progression of human tumors. Amplification and/or overexpression of ErbB2 have been reported in numerous cancers, including breast, ovarian, stomach, bladder, salivary, and lung cancers. As ErbB2 has been used as a target for the treatment of advanced cancer, RNA aptamers for the extracellular domain of the ErbB2 were selected from a RNA library consisting of 2'-fluorine-modified RNA transcripts. After 15 cycles of selection, high-affinity RNA aptamer was isolated. Binding patterns of the selected RNA aptamer clones were evaluated to choose RNA aptamers that were specific to the extracellular domain of ErbB2 protein. RNA aptamer 15-8 was the best candidate and its minimal version (mini-aptamer) was chemically synthesized. Surface plasmon resonance measurement showed that the mini-aptamer specifically bound to the ErbB2 protein with high affinity and specificity. To evaluate its potential as an ErbB2-targeting molecule in breast cancer cells, specific recognition of the mini-aptamer was confirmed with various breast cancer cell lines. We propose that the selected RNA aptamer is a potential cancer imaging agent by targeting malignant cells overexpressing the ErbB2 receptor.


Safety, Pharmacokinetics and Pharmacodynamics of Hetrombopag Olamine, a Novel TPO-R Agonist, in Healthy Individuals.
Hetrombopag olamine (hetrombopag) is a novel small-molecule, orally bioavailable, non-peptide thrombopoietin (TPO) receptor agonist that is being developed as the treatment for thrombocytopenia. Two randomized, placebo-controlled phase I studies were conducted in 72 healthy individuals to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of hetrombopag. Hetrombopag was orally administered with a single dose in five dose cohorts (5 mg, 10 mg, 20 mg, 30 mg or 40 mg) in the first study, and given once daily for 10 days in three dose cohorts (2.5 mg, 5.0 mg or 7.5 mg) in the second study, respectively. Hetrombopag was well tolerated, and the majority of adverse events associated with medicine were platelet elevations significantly above the normal range in healthy individuals. The single dose-escalation study revealed a Tmax of approximate 8 hr, and a t1/2 of 11.9 hr to 40.1 hr in a dose-prolonged manner. A dose-proportional increase in maximum concentration (Cmax ) of hetrombopag was observed, with area under the curve (AUC) increasing in a greater than dose-proportional manner. The plasma concentration of hetrombopag reached the steady-state after 7 days. The steady-state AUC0-24 hr and Cmax were dose-proportionally elevated from the 5.0 mg to 7.5 mg dose level. The potent pharmacological effect of the hetrombopag-induced platelet elevation was observed in a time- and dose-dependent manner. Furthermore, the thrombopoietic response was significantly (p < 0.0001) correlated to the plasma exposure level of hetrombopag in single and multiple administration studies. Taken together, results of this study support further clinical development of hetrombopag in patients with thrombocytopenia.


Electromyographic changes of agonist and antagonist calf muscles during maximum isometric induced fatigue.
The purpose of this study was to examine electromyographic changes of the agonist and antagonist muscles during fatigue. Nine healthy, untrained subjects exerted a maximum voluntary heel lifting contraction with their dominant limb. The EMG activity over the soleus and the tibialis anterior muscles was recorded during the contraction. The results showed that the torque output during heel lifting and the soleus EMG activity decreased, whereas the tibialis anterior EMG revealed a small but non-significant decrease. However, the ratio of the tibialis anterior to the soleus EMG increased significantly at the end of the fatigue protocol, a fact that reveals that the decrease rate of the antagonist's activity was significantly lower than the decrease rate of the agonist activity. It is concluded that during a maximal fatigue protocol, both the agonist and antagonist muscle activity may decline, however, the slower rate of antagonist's activity decrease relative to the agonist's activity is a finding that requires further investigation. This finding may reflect a higher level of agonist and antagonist muscle co-activation and probably a relatively higher opposing torque from the antagonist muscles at the end of the fatigue session.


Antimicrobial susceptibility and presence of extrachromosomal deoxyribonucleic acid in Salmonella and Shigella isolates from patients with AIDS.
The development of multi-drug resistance by enteric bacteria is an increasing problem in the developing countries. There is need to monitor antimicrobial susceptibility of these organisms in order to ensure appropriate treatment and control of infections. Antimicrobial susceptibility patterns, plasmid DNA content and restriction enzyme digests of plasmid deoxyribonucleic acid (DNA) were used to study 175 Salmonella and Shigella species isolated from predominantly HIV-seropositive adult patients in Nairobi, Kenya. All the isolates were sensitive to ciprofloxacin. A significantly higher proportion of Shigella species were resistant to chloramphenicol, cotrimoxazole, streptomycin and tetracycline compared to Salmonella species (p-value < 0.001). Multi-resistant Salmonella typhimurium isolates had 60, 40 and 5 MDa plasmids, the 5 MDa plasmid was absent in gentamicin sensitive isolates. In addition to 2-10 MDa range of plasmids, multi-resistant Shigella species had a heavy 100-105 MDa plasmid. Restriction enzyme digests were similar for the 60 and 40 MDa plasmid DNA bands from Salmonella typhimurium isolates but did not show any consistency among Shigella spp. Plasmid-encoded multi-drug resistance plays a major role in the spread of resistance among enteric bacteria. It is vital to use drugs rationally in order to control the emergence and spread of multi-drug resistance.


Effects of Macromolecular Crowding on Alcohol Dehydrogenase Activity Are Substrate-Dependent.
Enzymes operate in a densely packed cellular environment that rarely matches the dilute conditions under which they are studied. To better understand the ramifications of this crowding, the Michaelis-Menten kinetics of yeast alcohol dehydrogenase (YADH) were monitored spectrophotometrically in the presence of high concentrations of dextran. Crowding decreased the maximal rate of the reaction by 40% for assays with ethanol, the primary substrate of YADH. This observation was attributed to slowed release of the reduced β-nicotinamide adenine dinucleotide product, which is rate-limiting. In contrast, when larger alcohols were used as the YADH substrate, the rate-limiting step becomes hydride transfer and crowding instead increased the maximal rate of the reaction by 20-40%. This work reveals the importance of considering enzyme mechanism when evaluating the ways in which crowding can alter kinetics.


The association of psychopathology with concurrent level of functioning and subjective well-being in persons with schizophrenia spectrum disorders.
The objective is to investigate the relationship between psychopathology measured by the positive and negative syndrome scale (PANSS) and concurrent global assessment of functioning (GAF) and subjective well-being under neuroleptics (SWN) in patients with schizophrenia spectrum disorder (SSD) regarding severity of illness and disease phase. We analyzed a sample of 202 SSD patients consisting of first episode psychosis (FEP) and multiple episode psychosis (MEP) patients followed up to 12 months using linear mixed models. All PANSS syndromes except excitement were associated with GAF scores (positive syndrome: p < 0.001, d = 1.21; negative syndrome: p = 0.029, d = 0.015; disorganized syndrome: p < 0.001, d = 0.37; anxiety/depression syndrome: p < 0.001, d = 0.49), and positive symptoms had an increasing impact on global functioning with higher severity of illness (mildly ill: p = 0.039, d = 0.22; moderately ill: p < 0.001, d = 0.28; severely ill: p < 0.001, d = 0.69). SWN was associated with positive (p = 0.002, d = 0.22) and anxiety/depression (p < 0.001, d = 0.38) syndromes. Subgroup analyses showed differing patterns depending on illness severity and phase. Over all our results show different patterns of associations of psychopathology and concurrent functioning and subjective well-being. These findings contribute knowledge on the possible role of specific psychopathological syndromes for the functioning and well-being of our patients and may enable tailored treatments depending on severity and phase of illness.


CAPER as a therapeutic target for triple negative breast cancer.
Breast cancers (BCas) that lack expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are referred to as triple negative breast cancers (TNBCs) and have the poorest clinical outcome. Once these aggressive tumors progress to distant organs, the median survival decreases to 12 months. With endocrine therapies being ineffective in this BCa subtype, highly toxic chemo- and radiation therapies are the only options. A better understanding of the functional role(s) of molecular targets contributing to TNBC progression could help in the design and development of new treatments that are more targeted with less toxicity. CAPER (Co-activator of AP-1 and ER) is a nuclear transcriptional co-activator that was recently involved in ER-positive BCa progression, however its role in hormone-independent cancers remains unknown. Our current report demonstrates that CAPER expression is upregulated in human TNBC specimens compared to normal breast tissue and that its selective downregulation through a lentiviral-mediated shRNA knockdown approach resulted in decreased cell numbers in MDA-MB-231 and BT549 TNBC cell lines without affecting the growth of non-tumorigenic cell line MCF-10A. Concordant with these observations, CAPER knockdown was also associated with a decrease in DNA repair proteins leading to a marked increase in apoptosis, through caspase-3/7 activation without any changes in cell cycle. Collectively, we propose CAPER as an important signaling molecule in the development of TNBC linked to DNA repair mechanisms, which could lead to new therapeutic modalities for the treatment of this aggressive cancer.


Hepatoprotective Role of Berberine on Doxorubicin Induced Hepatotoxicity - Involvement of Cyp.
The liver is one of the major organ involved in drug metabolism. Cytochrome P450s are predominantly involved in drug metabolism. A wide range of CYPs have been reported in the liver which have been involved in its normal as well as in diseased conditions. Doxorubicin, one of the most potent chemotherapeutic drugs, although highly efficacious, also has adverse side effects, with its targets being liver and cardiac tissue. The study aims to evaluate the reversal potentials of berberine on Doxorubicin induced cyp conversion. In the present study, the interplay between anti-oxidants, cytochrome and inflammatory markers in DOX induced liver toxicity and its possible reversal by berberine was ascertained. DOX administration significantly elevated serum as well as tissue stress, which was reverted by berberine treatment. A similar response was observed in tissue inflammatory mediators as well as in serum cytokine levels. Most profound reduction in the cytochrome expression was found in Cyp 2B1, 2B2, and 2E1. However, 2C1, 2C6, and 3A1 although showed a decline, but it did not revert the expression back to control levels. It could be concluded that berberine may be an efficient anti-oxidant and immune modulator. It possesses low to moderate cytochrome modulatory potentials.


"Why Did She Talk to Him Again?" The Effects of the Justice Motive, Relationship Type, and Degree of Postassault Contact on Perceptions of Sexual Assault.
Victim blaming attitudes are prevalent within the criminal justice system where survivor behavior before, during, and following an assault is heavily scrutinized. Although dispositional characteristics (e.g., strength of one's justice motive) and characteristics of the assault (e.g., the type of relationship between a survivor and an offender) have been found to predict the degree of victim blaming, the effects of these variables on sexual assault myth endorsement are unclear. In addition, a variable that has not been examined in past literature is the degree of contact maintained between a survivor and offender after the assault. The purpose of the current study was to examine the extent to which the justice motive (strong vs. weak), the relationship between a fictional survivor and an offender (strangers vs. intimate partners), and contact between a survivor and offender postassault (contact vs. no contact) influenced endorsement of sexual assault myths. Undergraduate students read a vignette depicting a fictional sexual assault that varied with respect to the relationship and the amount of postassault contact between the survivor and offender and completed measures of the strength of their justice motive and their endorsement of sexual assault myths. Results indicated that participants (N = 419) who held a strong justice motive showed higher endorsement of sexual assault myths. Participants were also more likely to endorse sexual assault myths when there was postoffense contact between the survivor and offender. The implications of these findings and their relevance to the criminal justice system are discussed, including the need for further research into the creation of survivor-oriented education and training capable of counteracting bias toward survivors of sexual violence and producing sustained attitudinal changes.


Autoantibodies against a 210 kDa glycoprotein of the nuclear pore complex as a prognostic marker in patients with primary biliary cirrhosis.
It has been reported that the presence of anti-nuclear antibody against a 210 kDa glycoprotein of nuclear pore complex (anti-gp210) is highly specific for primary biliary cirrhosis (PBC). The aim of the present study was to investigate the significance of anti-gp210, especially as a prognostic marker. The presence of anti-gp210 was ascertained in 113 patients with PBC and 162 controls by indirect immunofluorescence assay using HepG2 cells and immunoblotting analysis using nuclear extracts from HeLa cells. Anti-gp210 was detected in 25 of the 113 (22.1%) patients. None of the 162 controls was positive for anti-gp210. The appearance and titre of anti-gp210 in the patients with PBC did not vary from the time of diagnosis and through their clinical course. Anti-mitochondrial antibodies (AMA), including antibodies against pyruvate dehydrogenase complex, branched chain alpha-ketoacid dehydrogenase complex and alpha-ketoglutarate dehydrogenase complex, were not detected by enzyme-linked immunosorbent assay in five of the 113 (4.4%) patients with PBC. However, anti-gp210 alone was positive in one of these five patients. The difference in prognosis was statistically significant; patients with PBC positive for anti-gp210 died from hepatic failure more frequently than those who were negative (P < 0.01), although there were no statistically significant differences in the frequency of jaundice and the histological stage at the time of diagnosis between the two groups. We suggest that the presence of anti-gp210 is one of the independent prognostic markers able to predict, at the time of diagnosis, a poor outcome in patients with PBC.


Betamipron reduces cisplatin nephrotoxicity in rodents without modifying its antileukemic activity in mice.
Protective effects of betamipron (BP, N-benzoyl-beta-alanine), one of a series of N-acyl amino acids, on cisplatin-induced nephrotoxicity were examined. Since the damage observed in the kidney is localized to the proximal tubule cells, we investigated the influence of BP on urinary enzymes and excreta. Male Wistar rats and ddY mice were injected i.p. with 6 mg/kg and 16 mg/kg, respectively, of cisplatin combined with an i.p. 250 mg/kg BP dose. The toxicity of cisplatin as indicated by body weight gain, blood urea nitrogen, and serum creatinine levels was significantly (p < 0.05) suppressed by administration of BP after cisplatin treatment. The increase in urinary N-acetyl-beta-D-glucosaminidase activity, increase and subsequent decrease in gamma-glutamyl transferase activities, and increase in beta 2-microglobulin level observed after treatment with cisplatin were suppressed by administration of BP after cisplatin treatment. The combination of cisplatin and BP had no apparent effect on the efficacy of cisplatin against P388 leukemic cells in mice.


The Role of Somatic L1 Retrotransposition in Human Cancers.
The human LINE-1 (or L1) element is a non-LTR retrotransposon that is mobilized through an RNA intermediate by an L1-encoded reverse transcriptase and other L1-encoded proteins. L1 elements remain actively mobile today and continue to mutagenize human genomes. Importantly, when new insertions disrupt gene function, they can cause diseases. Historically, L1s were thought to be active in the germline but silenced in adult somatic tissues. However, recent studies now show that L1 is active in at least some somatic tissues, including epithelial cancers. In this review, we provide an overview of these recent developments, and examine evidence that somatic L1 retrotransposition can initiate and drive tumorigenesis in humans. Recent studies have: (i) cataloged somatic L1 activity in many epithelial tumor types; (ii) identified specific full-length L1 source elements that give rise to somatic L1 insertions; and (iii) determined that L1 promoter hypomethylation likely plays an early role in the derepression of L1s in somatic tissues. A central challenge moving forward is to determine the extent to which L1 driver mutations can promote tumor initiation, evolution, and metastasis in humans.


ICP-AES Determination of Mineral Content in Boletus tomentipes Collected from Different Sites of China.
P, Na, Ca, Cu, Fe, Mg, Zn, As, Cd, Co, Cr and Ni, contents have been examined in caps and stipes of Boletus tomentipes collected from different sites of Yunnan province, southwest China. The elements were determined using inductively coupled plasma atomic emission spectroscopy (ICP-AES) with microwave digestion. P, Ca, Mg, Fe, Zn and Cu were the most abundant amongst elements determined in Boletus tomentipes. The caps were richer in P, Mg, Zn and Cd, and the stipes in Ca, Co and Ni. Cluster analysis showed a difference between Puer (BT7 and BT8) and other places. The PCA explained about 77% of the total variance, and the minerals differentiating these places were P (PC1) together with Ca, Cu, Fe, Mg, As and Ni, Na (PC2) together with Cd, and Zn (PC3). The results of this study imply that element concentrations of a mushroom are mutative when collected from the different bedrock soil geochemistry.