The Effect of Pseudomonas putida Colonization on Root Surface Peroxidase.
Increased activities of peroxidase and indole 3-acetic acid (IAA) oxidase were detected on root surfaces of bean (Phaseolus vulgaris) seedlings colonized with a soil saprophytic bacterium, Pseudomonas putida. IAA oxidase activity increased over 250-fold and peroxidase 8-fold. Enhancement was greater for 6-day-old than for 4- or 8-day-old inoculated plants No IAA oxidase or peroxidase activities were associated with the bacterial cells. Native polyacrylamide gel electrophoresis demonstrated that washes of P. putida-inoculated roots contained two zones of peroxidase activity. Only the more anodic bands were detected in washes from noninoculated roots. Ion exchange and molecular sizing gel chromatography of washes from P. putida-colonized roots separated two fractions of peroxidase activity. One fraction corresponded to the anodic bands detected in washes of P. putida inoculated and in noninoculated roots. A second fraction corresponded to the less anodic zone of peroxidase, which was characteristic of P. putida-inoculated plants. This peroxidase had a higher IAA oxidase to peroxidase ratio than the more anodic, common enzyme. The changes in root surface peroxidases caused by colonization by a saprophytic bacterium are discussed with reference to plant-pathogen interactions.


Translocator protein (TSPO) ligands for the diagnosis or treatment of neurodegenerative diseases: a patent review (2010-2015; part 1).
The translocator protein (TSPO) is an emerging target in diverse neurodegenerative diseases. Up-regulated TSPO in the central nervous system (CNS) appears to be involved in neuroinflammatory processes; therefore, the development of potent TSPO ligands is a promising method for alleviating or imaging patients with neurodegenerative diseases. Areas covered: This review will provide an overview of recently developed TSPO ligands patented from 2010 to 2015. Part 1 will present a summary focusing on TSPO ligands other than indole-based or cholesterol-like compounds, which will be discussed in part 2. Part 1 covers diverse benzodiazepine-derived analogues such as isoquinoline carboxamides and aryloxyanilides. Moreover, bicyclic ring structures such as imidazopyridine, pyrazolopyrimidine, and phenylpurine will be highlighted as promising scaffolds for TSPO ligands. A brief analysis of currently reported TSPO structures will also be covered in part 1. Expert opinion: Although the underlying pharmacological mechanism of TSPO remains to be elucidated, several TSPO ligands have shown therapeutic efficacy in experimental animal models of neurodegenerative diseases. In addition, radioactive TSPO ligands have been extensively studied for the diagnosis of neurodegenerative processes. Thus, further studies on both the basic and applied mechanisms of TSPO are warranted in the pursuit of successful pharmacological applications of TSPO ligands.


Prenatal screening for illegal drugs. Dilemma for the nurse-midwife.
Prenatal screening for illegal drugs poses very complex ethical problems for the nurse-midwife who must make the decision whether to screen for illegal drugs and whether to report positive results to state child abuse investigators. We argue that the results of prenatal screening for illegal drug use should not be used for determination of child abuse and that the nurse-midwife should not be required to report the results of these screens for illegal drugs to state child protection agencies. It is far from clear that required reporting offers any benefit to the fetus or future child, and there are serious ramifications of reporting for the fetus, the pregnant woman, and the nurse-midwifery profession. However, we do argue that prenatal screening for both illegal and legal drug use should be encouraged and should be done as early as possible in the pregnancy. Prenatal screening for drugs should only be used by the nurse-midwife as a diagnostic procedure wherein standard informed consent and confidentiality restraints are maintained.


Glutaraldehyde-polymerized bovine hemoglobin and phosphodiesterase-5 inhibition.
Hemoglobin-based oxygen carriers (HBOC) of several types scavenge nitric oxide from the vasculature resulting in vasoconstriction and hypertension, both systemic and pulmonary. Phosphodiesterase-5 (PDE5) inhibitors promote nitric oxide activity and enhance vasodilation. The purpose of this study was to determine whether combined therapy of glutaraldehyde-polymerized bovine hemoglobin (HBOC) with a PDE5 inhibitor would counter the negative hemodynamic consequences of HBOC therapy alone, resulting in improved hemodynamics and oxygen delivery. A controlled, experimental study. A research laboratory at a university. Conscious male Sprague-Dawley rats. Glutaraldehyde-polymerized bovine hemoglobin (HBOC), sildenafil (PDE5 inhibitor), and lactated Ringer's solution (control). Infusion of the HBOC resulted in significant (p < 0.05) systemic and pulmonary vasoconstriction, with reduced cardiac output and reduced oxygen delivery to the periphery. Infusion of lactated Ringer's demonstrated no changes in the measured variables. Infusion of sildenafil alone reduced systemic and pulmonary artery blood pressure, while maintaining cardiac output and oxygen delivery. Combined HBOC and sildenafil infusion resulted in stable systemic blood pressure, cardiac output, and oxygen delivery. However, the addition of sildenafil to HBOC did not fully ameliorate the pulmonary vasoconstriction caused by HBOC. The HBOC used in this study resulted in pulmonary and systemic hypertension, reduced cardiac output, and oxygen delivery. These negative consequences of HBOC treatment can be largely overcome by combing HBOC treatment with a PDE5 inhibitor (sildenafil). Thus, these data support the continued investigation of combined HBOC and PDE5 inhibitor treatment in circumstances in which HBOC therapy is being considered.


Imaging Assessment of Pancreatic Cancer Resectability After Neoadjuvant Therapy: AJR Expert Panel Narrative Review.
Despite important innovations in the treatment of pancreatic ductal adenocarcinoma (PDAC), PDAC remains a disease with poor prognosis and high mortality. A key area for potential improvement in the management of PDAC, aside from earlier detection in patients with treatable disease, is the improved ability of imaging techniques to differentiate treatment response after neoadjuvant therapy (NAT) from worsening disease. It is well established that current imaging techniques cannot reliably make this distinction. This narrative review provides an update on the imaging assessment of pancreatic cancer resectability after NAT. Current definitions of borderline resectable PDAC, as well as implications for determining likely patient benefit from NAT, are described. Challenges associated with PDAC pathologic evaluation and surgical decision making that are of relevance to radiologists are discussed. Also explored are the specific limitations of imaging in differentiating the response after NAT from stable or worsening disease, including issues relating to protocol optimization, tumor size assessment, vascular assessment, and liver metastasis detection. The roles of MRI as well as PET and/or hybrid imaging are considered. Finally, a short PDAC reporting template is provided for use after NAT. The highlighted methods seek to improve radiologists' assessment of PDAC treatment response after NAT.


Estrogen receptors alpha and beta in the rodent mammary gland.
An obligatory role for estrogen in growth, development, and functions of the mammary gland is well established, but the roles of the two estrogen receptors remain unclear. With the use of specific antibodies, it was found that both estrogen receptors, ERalpha and ERbeta, are expressed in the rat mammary gland but the presence and cellular distribution of the two receptors are distinct. In prepubertal rats, ERalpha was detected in 40% of the epithelial cell nuclei. This decreased to 30% at puberty and continued to decrease throughout pregnancy to a low of 5% at day 14. During lactation there was a large induction of ERalpha with up to 70% of the nuclei positive at day 21. Approximately 60-70% of epithelial cells expressed ERbeta at all stages of breast development. Cells coexpressing ERalpha and ERbeta were rare during pregnancy, a proliferative phase, but they represented up to 60% of the epithelial cells during lactation, a postproliferative phase. Western blot analysis and sucrose gradient centrifugation confirmed this pattern of expression. During pregnancy, the proliferating cell nuclear antigen was not expressed in ERalpha-positive cells but was observed in 3-7% of ERbeta-containing cells. Because more than 90% of ERbeta-bearing cells do not proliferate, and 55-70% of the dividing cells have neither ERalpha nor ERbeta, it is clear that the presence of these receptors in epithelial cells is not a prerequisite for estrogen-mediated proliferation.


Natural prostaglandins for induction of labor and preinduction cervical ripening.
Prostaglandin (PG) E2 has superseded all other natural prostaglandins for induction of labor and pre-induction cervical ripening. This evolution and its rationale are briefly described. PGE2 has been administered intravenously, orally, vaginally, endocervically, and extra-amniotically for induction of labor. All of these, except the intravenous route, have also been explored for pre-induction cervical ripening. The distinction between formal induction and pre-induction is not always clearly made with many studies pursuing both goals at once. Nevertheless, the effectiveness of PGE2 to achieve ripening and induction is currently beyond doubt. In women with unfavorable induction prospects PGE2 results in lower rates of failed induction and higher rates of delivery within a reasonable interval than amniotomy and/or oxytocin. This also applies to women with prelabor rupture of the membranes, but the relative advantages of PGE2 over traditional methods are less clear for women with a favorable cervix. Vaginal administration of PGE2 has superseded virtually all other routes of PGE2 administration except the endocervical route, which tends to give variable results depending on spillage from the endocervical canal. Doses and formulations of vaginal PGE2 with various gels, tablets, pessaries and slow release inserts have varied widely and continue to do so. There is currently no evidence for the superiority of one PGE2 preparation over another.


Synchronous protein cycling in batch cultures of the yeast Saccharomyces cerevisiae at log growth phase.
The assumption that cells are temporally organized systems, i.e. showing relevant dynamics of their state variables such as gene expression or protein and metabolite concentration, while tacitly given for granted at the molecular level, is not explicitly taken into account when interpreting biological experimental data. This conundrum stems from the (undemonstrated) assumption that a cell culture, the actual object of biological experimentation, is a population of billions of independent oscillators (cells) randomly experiencing different phases of their cycles and thus not producing relevant coordinated dynamics at the population level. Moreover the fact of considering reproductive cycle as by far the most important cyclic process in a cell resulted in lower attention given to other rhythmic processes. Here we demonstrate that growing yeast cells show a very repeatable and robust cyclic variation of the concentration of proteins with different cellular functions. We also report experimental evidence that the mechanism governing this basic oscillator and the cellular entrainment is resistant to external chemical constraints. Finally, cell growth is accompanied by cyclic dynamics of medium pH. These cycles are observed in batch cultures, different from the usual continuous cultures in which yeast metabolic cycles are known to occur, and suggest the existence of basic, spontaneous, collective and synchronous behaviors of the cell population as a whole.


Accuracy of Digital Breast Tomosynthesis for Depicting Breast Cancer Subgroups in a UK Retrospective Reading Study (TOMMY Trial).
To compare the diagnostic performance of two-dimensional (2D) mammography, 2D mammography plus digital breast tomosynthesis (DBT), and synthetic 2D mammography plus DBT in depicting malignant radiographic features. In this multicenter, multireader, retrospective reading study (the TOMMY trial), after written informed consent was obtained, 8869 women (age range, 29-85 years; mean, 56 years) were recruited from July 2011 to March 2013 in an ethically approved study. From these women, a reading dataset of 7060 cases was randomly allocated for independent blinded review of (a) 2D mammography images, (b) 2D mammography plus DBT images, and (c) synthetic 2D mammography plus DBT images. Reviewers had no access to results of previous examinations. Overall sensitivities and specificities were calculated for younger women and those with dense breasts. Overall sensitivity was 87% for 2D mammography, 89% for 2D mammography plus DBT, and 88% for synthetic 2D mammography plus DBT. The addition of DBT was associated with a 34% increase in the odds of depicting cancer (odds ratio [OR] = 1.34, P = .06); however, this level did not achieve significance. For patients aged 50-59 years old, sensitivity was significantly higher (P = .01) for 2D mammography plus DBT than it was for 2D mammography. For those with breast density of 50% or more, sensitivity was 86% for 2D mammography compared with 93% for 2D mammography plus DBT (P = .03). Specificity was 57% for 2D mammography, 70% for 2D mammography plus DBT, and 72% for synthetic 2D mammography plusmDBT. Specificity was significantly higher than 2D mammography (P < .001in both cases) and was observed for all subgroups (P < .001 for all cases). The addition of DBT increased the sensitivity of 2D mammography in patients with dense breasts and the specificity of 2D mammography for all subgroups. The use of synthetic 2D DBT demonstrated performance similar to that of standard 2D mammography with DBT. DBT is of potential benefit to screening programs, particularly in younger women with dense breasts. (©) RSNA, 2015.


The Modified Medial Maxillectomy as a Radical or Extended,-yet Still Functional,-Technique in Sinus Surgery.
Endoscopic sinus surgery with a middle meatal antrostomy is a common intervention in the treatment algorithm for maxillary sinus pathologies. However, this procedure has its origins in a time when simple ventilation of the sinus cavity was the primary (and only often) goal of surgery. In some patients, persistent mucociliary dysfunction occurs despite ventilatory surgery. Although the endoscopic modified medial maxillectomy (MMM) was originally described for tumour surgery, it provides a radical yet still functional option to overcome chronic sinus dysfunction. The goal of this study was to describe the functional status of a post-MMM sinus cavity. A consecutive series of patients who underwent at least a unilateral MMM by three tertiary rhinologists were retrospectively reviewed. Prospectively collected data included patient demographics (including age, gender, smoking status and comorbidities), disease-specific factors, microbiology, and preoperative patient-reported symptoms based on the 22-item Sinonasal Outcome Test-22 (SNOT-22) and radiology. The primary outcome of the study was the presence of sinus dysfunction, defined by mucostasis or pooling on endoscopic examination at the last follow-up. Secondary outcomes included the need for revision surgery as a result of sinus dysfunction and the improvement in SNOT-22 score. A total of 551 medial maxillectomies (47.0% female, 52.9 ± 16.8 years) were performed. Very few patients experienced post-operative sustained mucostasis following MMM (10.2%) and even fewer required revision surgery (5.0%). Chronic obstructive pulmonary disease (odds ratio (OR) = 6.82, P < 0.002.) and asthma (OR = 2.48, P = 0.03) were associated with mucostasis. Patients who underwent an MMM experienced a notable postoperative improvement in SNOT-22 score (45.9 ± 23.7 (pre-op) vs. 23.6 ± 19.4 (post-op); paired t-test, P < 0.0001). The MMM, whether performed for access to pathology or with the intent to avoid mucous 'sumping' with the sinus, can provide a long-term functional maxillary sinus cavity with minimal morbidity.


The role of capsaicin-sensitive C-fibre afferent nerves in the cough reflex.
While airway rapidly adapting receptors can mediate the cough reflex, much evidence suggests that bronchial C-fibre receptors are also involved in guinea-pigs and man. In man local and systemic C-fibre stimulants have a potent tussive action, which is blocked by low doses of local anaesthetics which leave the reflex bronchoconstriction intact. In guinea-pigs destruction of airway C-fibre receptors by large doses of capsaicin abolishes the cough reflex due to capsaicin and citric acid. Thus there may be subpopulations of airway C-fibres responsible for the different reflexes such as apnoea, cough and bronchoconstriction. The evidence for the role of C-fibre receptors in cough is described and discussed.


Marrow involvement with T cell lymphoma initially presenting as abnormal myelopoiesis.
Three cases of T cell lymphoma affecting the marrow, in which initial bone marrow appearances were misleading, occurred. In each case the initial clinical presentation was related to cytopenia, but the marrow abnormalities at this time suggested an abnormal myeloid proliferative state, with no evidence of a malignant lymphoid proliferation. Later in the course of the disease, however, the characteristic pattern of marrow infiltration by mature post-thymic T cells became evident. The consequent delay (two to 36 months) in diagnosis was noted.


Trade-off Predictivity and Explainability for Machine-Learning Powered Predictive Toxicology: An in-Depth Investigation with Tox21 Data Sets.
Selecting a model in predictive toxicology often involves a trade-off between prediction performance and explainability: should we sacrifice the model performance to gain explainability or vice versa. Here we present a comprehensive study to assess algorithm and feature influences on model performance in chemical toxicity research. We conducted over 5000 models for a Tox21 bioassay data set of 65 assays and ∼7600 compounds. Seven molecular representations as features and 12 modeling approaches varying in complexity and explainability were employed to systematically investigate the impact of various factors on model performance and explainability. We demonstrated that end points dictated a model's performance, regardless of the chosen modeling approach including deep learning and chemical features. Overall, more complex models such as (LS-)SVM and Random Forest performed marginally better than simpler models such as linear regression and KNN in the presented Tox21 data analysis. Since a simpler model with acceptable performance often also is easy to interpret for the Tox21 data set, it clearly was the preferred choice due to its better explainability. Given that each data set had its own error structure both for dependent and independent variables, we strongly recommend that it is important to conduct a systematic study with a broad range of model complexity and feature explainability to identify model balancing its predictivity and explainability.


Data mining graphene: correlative analysis of structure and electronic degrees of freedom in graphenic monolayers with defects.
The link between changes in the material crystal structure and its mechanical, electronic, magnetic and optical functionalities-known as the structure-property relationship-is the cornerstone of modern materials science research. The recent advances in scanning transmission electron and scanning probe microscopies (STEM and SPM) have opened an unprecedented path towards examining the structure-property relationships of materials at the single-impurity and atomic-configuration levels. However, there are no statistics-based approaches for cross-correlation of structure and property variables obtained from the different information channels of STEM and SPM experiments. Here we have designed an approach based on a combination of sliding window fast Fourier transform, Pearson correlation matrix and linear and kernel canonical correlation methods to study the relationship between lattice distortions and electron scattering from SPM data on graphene with defects. Our analysis revealed that the strength of coupling to strain is altered between different scattering channels, which can explain the coexistence of several quasiparticle interference patterns in nanoscale regions of interest. In addition, the application of kernel functions allowed us to extract a non-linear component of the relationship between the lattice strain and scattering intensity in graphene. The outlined approach can be further used to analyze correlations in various multi-modal imaging techniques where the information of interest is spatially distributed and generally has a complex multi-dimensional nature.


Large-scale production of diesel-like biofuels - process design as an inherent part of microorganism development.
Industrial biotechnology is playing an important role in the transition to a bio-based economy. Currently, however, industrial implementation is still modest, despite the advances made in microorganism development. Given that the fuels and commodity chemicals sectors are characterized by tight economic margins, we propose to address overall process design and efficiency at the start of bioprocess development. While current microorganism development is targeted at product formation and product yield, addressing process design at the start of bioprocess development means that microorganism selection can also be extended to other critical targets for process technology and process scale implementation, such as enhancing cell separation or increasing cell robustness at operating conditions that favor the overall process. In this paper we follow this approach for the microbial production of diesel-like biofuels. We review current microbial routes with both oleaginous and engineered microorganisms. For the routes leading to extracellular production, we identify the process conditions for large scale operation. The process conditions identified are finally translated to microorganism development targets. We show that microorganism development should be directed at anaerobic production, increasing robustness at extreme process conditions and tailoring cell surface properties. All the same time, novel process configurations integrating fermentation and product recovery, cell reuse and low-cost technologies for product separation are mandatory. This review provides a state-of-the-art summary of the latest challenges in large-scale production of diesel-like biofuels.


Bayesian optimal interval design for dose finding in drug-combination trials.
Interval designs have recently attracted enormous attention due to their simplicity and desirable properties. We develop a Bayesian optimal interval design for dose finding in drug-combination trials. To determine the next dose combination based on the cumulative data, we propose an allocation rule by maximizing the posterior probability that the toxicity rate of the next dose falls inside a prespecified probability interval. The entire dose-finding procedure is nonparametric (model-free), which is thus robust and also does not require the typical "nonparametric" prephase used in model-based designs for drug-combination trials. The proposed two-dimensional interval design enjoys convergence properties for large samples. We conduct simulation studies to demonstrate the finite-sample performance of the proposed method under various scenarios and further make a modication to estimate toxicity contours by parallel dose-finding paths. Simulation results show that on average the performance of the proposed design is comparable with model-based designs, but it is much easier to implement.


"Shovel-ready" Sequences as a Stimulus for the Next Generation of Life Scientists.
Genomics and bioinformatics are dynamic fields well-suited for capturing the imagination of undergraduates in both research laboratories and classrooms. Currently, raw nucleotide sequence is being provided, as part of several genomics research initiatives, for undergraduate research and teaching. These initiatives could be easily extended and much more effective if the source of the sequenced material and the subsequent focus of the data analysis were aligned with the research interests of individual faculty at undergraduate institutions. By judicious use of surplus capacity in existing nucleotide sequencing cores, raw sequence data could be generated to support ongoing research efforts involving undergraduates. This would allow these students to participate actively in discovery research, with a goal of making novel contributions to their field through original research while nurturing the next generation of talented research scientists.


Proteomics: a novel tool to unravel the patho-physiology of uraemia.
Uraemic toxicity results in the dysfunction of many organ systems, provoking an increase in morbidity and mortality. To date, only approximately 90 uraemic retention solutes have been described. To examine unknown uraemic substances thoroughly, the identification of as many compounds as possible in the ultrafiltrate and/or plasma of patients would lead to a less biased definition of the uraemic retention process compared with what is proposed today. We describe the application of a novel proteomic tool for the identification of a large number of molecules present in ultrafiltrate from uraemic and normal plasma obtained with high- or low-flux membranes. Separation by capillary electrophoresis was coupled on-line to a mass spectrometer, yielding identification of polypeptides based on their molecular weight. Between 500 and >1000 polypeptides with a molecular weight ranging from 800 to 10,000 Da could be detected in individual samples, and were identified via their mass and their particular migration time in capillary electrophoresis. In ultrafiltrate from uraemic plasma, 1394 polypeptides were detected in the high-flux vs 1046 in the low-flux samples, while in ultrafiltrate from normal plasma, 544 polypeptides vs 490 were found in ultrafiltrate from normal plasma obtained from membranes with comparable cut-off. In addition, polypeptides >5 kDa were virtually only detected in the uraemic ultrafiltrate from the high-flux membrane (n = 28 vs n = 5 with the low-flux membrane). To demonstrate the feasibility of further characterizing the detected molecules, polypeptides present exclusively in uraemic ultrafiltrate were chosen for sequencing analyses. A 950.6 Da polypeptide was identified as a fragment of the salivary proline-rich protein. A 1291.8 Da fragment was derived from alpha-fibrinogen. The data presented here strongly suggest that the application of proteomic approaches such as capillary electrophoresis and mass spectrometry will result in the identification of many more uraemic solutes than those known at present. This could enable the introduction of more direct elimination strategies, since it is possible to obtain an extended appreciation of the removal capacities of particular dialyser membranes.


DENTISTS' MOBILE PHONES AS A MEANS OF SPREADING CONDITIONALLY PATHOGENS.
The aim: The aim of the study was to determine the level of bacterial contamination of mobile phones and watches of dentists. Materials and methods: The study was conducted at the University Dental Clinic and Microbiology Laboratory at the Department of Genetics, Plant Physiology and Microbiology of Uzhhorod National University. Swabs from the investigated surfaces of 30 mobile phones and 30 watches were collected using disposable sterile cotton swabs moistened with sterile saline. The clinical isolates were isolated with the use of differentially diagnostic nutrient media. Results: Studies have shown that cell phones are contaminated with pathogenic microorganisms to a much greater extent than watches. 1518 CFU were isolated from mobile phones, while 375 CFU from watches. The dominant representatives of the microflora of the studied objects were gram positive bacteria of the genus Staphylococcus. Comparative characteristics of the species composition of bacteria of the genus Staphylococcus isolated from mobile phones and watches showed that the dominant species isolated was S.epidemidis. Therefore, studies have shown a high degree of contamination of mobile phones with coagulase-positive bacteria of the genus Staphylococcus, which in most showed hemolytic properties. Conclusions: The patterns identified indicate that mobile phones can play a role in the spread of opportunistic infection.


[A successful surgical treatment of traumatic dissecting aneurysm].
Dissecting thoracic aortic aneurysm caused by blunt trauma was reported. A 64-year-old woman involved in automobile accident was transported to our hospital. Chest X-ray showed multiple rib fractures and enlargement of mediastinal shadow. Emergent CT scan and angiography (DSA) revealed aortic dissection (DeBakey IIIb). She suffered from acute renal and respiratory failure soon after admission, but underwent operation 6 months after the trauma because of enlargement of false channel. Graft replacement was performed and postoperative course was uneventful. Histopathologic findings showed dissection of adventitia of the aorta.


Favorable outcome for infant acute lymphoblastic leukemia after hematopoietic stem cell transplantation.
Infants with acute lymphoblastic leukemia (ALL) have a poor prognosis when treated with standard chemotherapy. A subset of these infants, particularly those with mixed-lineage leukemia (MLL) rearrangements, has a high likelihood of relapse. Hematopoietic stem cell transplantation (HSCT) performed early in first remission may improve outcome. We present the results of 16 patients with infant ALL who were treated with HSCT in first remission. Six patients were < or =6 months of age at diagnosis, 11 had an initial white blood cell count of >50000/microL, and all patients with determinable cytogenetics had a high-risk karyotype [t(4:11) abnormality or other MLL rearrangement]. All patients received 150 cGy of total body irradiation for 8 doses (1200 cGy). Fifteen of 16 patients received etoposide at 1000 mg/m(2) as a continuous infusion over 24 hours and cyclophosphamide at 60 mg/kg/d for 3 days. Eight patients received HSCT from an HLA-identical sibling, and 8, from unrelated cord blood. Twelve (75%) patients remain long-term survivors (median follow-up, 4.7 years). Two patients, 1 of whom had minimal residual disease at HSCT, died after relapse following HSCT. Two patients died of transplant-related causes. The HSCT was well tolerated; 15 patients achieved neutrophil engraftment at a median of 16 days. Acute and chronic graft-versus-host disease were minimal in these patients. These results support the use of HSCT in the treatment of infant ALL, especially when used as consolidation in first remission. The risk of relapse seems to be decreased with this approach. Further work is being performed to determine the long-term effects from this therapy.


Reasoning from memory: a lifespan inquiry into the necessity of remembering when reasoning about class inclusion.
In the current experiment, we evaluated the relationship between reasoning and remembering across the lifespan (10-, 13-, 15-, 23-, and 67-year-olds) using color and number class-inclusion tasks. Subjects made judgments when memory load or information load was either high or low. Reading latency, choice latency, and choice accuracy data were collected and analyzed using formal models that partitioned memory and reasoning as well as type of reasoning strategy. The results showed that: (1) study skills, as indexed by reading latency, were sophisticated across the lifespan; (2) the difference between color and number choice latencies increased with age; (3) reasonably consistent effects were obtained as a function of increasing memory load, with the quality of both reasoning and remembering being adversely affected; (4) different effects were obtained at each age as a function of increasing information load; and (5) the major developmental trend across the lifespan was a tradeoff between class-inclusion and subclass-subclass forms of reasoning. A number of extant theoretical approaches were discussed, none of which were able to account for variations in class-inclusion performance across the lifespan. What was clear, however, was that memory-reasoning dependencies must be incorporated into any comprehensive theory of cognitive development across the lifespan.


AnnapuRNA: A scoring function for predicting RNA-small molecule binding poses.
RNA is considered as an attractive target for new small molecule drugs. Designing active compounds can be facilitated by computational modeling. Most of the available tools developed for these prediction purposes, such as molecular docking or scoring functions, are parametrized for protein targets. The performance of these methods, when applied to RNA-ligand systems, is insufficient. To overcome these problems, we developed AnnapuRNA, a new knowledge-based scoring function designed to evaluate RNA-ligand complex structures, generated by any computational docking method. We also evaluated three main factors that may influence the structure prediction, i.e., the starting conformer of a ligand, the docking program, and the scoring function used. We applied the AnnapuRNA method for a post-hoc study of the recently published structures of the FMN riboswitch. Software is available at https://github.com/filipspl/AnnapuRNA.


Different effects of erythropoietin in cisplatin- and docetaxel-induced neurotoxicity: an in vitro study.
Chemotherapy-induced peripheral neurotoxicity (CIPN) is a side effect limiting cisplatin (CDDP) and docetaxel (DOCE) treatment. Erythropoietin (EPO) is a hematopoietic growth factor also displaying neurotrophic properties. Evidence suggests that EPO's neuroprotective action may rely on PI3K/AKT pathway activation; however, data regarding the EPO neuroprotective mechanism are still limited. This study evaluated the effect of EPO on organotypic cultures of rat dorsal root ganglia (DRG) and in primary cultures of DRG-dissociated sensory neurons exposed to CDDP- and DOCE-induced neurotoxicity, aiming to investigate EPO's neuroprotective mechanism. Subsequently, the levels of AKT expression and activation were analyzed by Western blot in neurons exposed to CDDP or DOCE; AKT's role was further evaluated by using a chemical inhibitor of AKT activation, wortmannin. In these models EPO, was protective against both CDDP- and DOCE-induced cell death and against CDDP-induced neurite elongation reduction. A modulation of AKT activation was observed in CDDP-treated neurons, and the presence of wortmannin prevented EPO's neuroprotective action against CDDP toxicity but did not have any effect on EPO's protection against DOCE-induced toxicity, thus ruling out the PI3K-AKT pathway as the mechanism of EPO's effect in neuronal death prevention after DOCE exposure. Our results confirm in vitro the effectiveness of EPO as a neuroprotectant against both CDDP- and DOCE-induced neurotoxicity. In addition, a role of PI3K/AKT in EPO's protection against CDDP, but not against DOCE, neurotoxicity was shown, suggesting that alternative pathways could be involved in EPO's neuroprotective activity.


Functional genomics of seed dormancy in wheat: advances and prospects.
Seed dormancy is a mechanism underlying the inability of viable seeds to germinate under optimal environmental conditions. To achieve rapid and uniform germination, wheat and other cereal crops have been selected against dormancy. As a result, most of the modern commercial cultivars have low level of seed dormancy and are susceptible to preharvest sprouting when wet and moist conditions occur prior to harvest. As it causes substantial loss in grain yield and quality, preharvest sprouting is an ever-present major constraint to the production of wheat. The significance of the problem emphasizes the need to incorporate an intermediate level of dormancy into elite wheat cultivars, and this requires detailed dissection of the mechanisms underlying the regulation of seed dormancy and preharvest sprouting. Seed dormancy research in wheat often involves after-ripening, a period of dry storage during which seeds lose dormancy, or comparative analysis of seeds derived from dormant and non-dormant cultivars. The increasing development in wheat genomic resources along with the application of transcriptomics, proteomics, and metabolomics approaches in studying wheat seed dormancy have extended our knowledge of the mechanisms acting at transcriptional and post-transcriptional levels. Recent progresses indicate that some of the molecular mechanisms are associated with hormonal pathways, epigenetic regulations, targeted oxidative modifications of seed mRNAs and proteins, redox regulation of seed protein thiols, and modulation of translational activities. Given that preharvest sprouting is closely associated with seed dormancy, these findings will significantly contribute to the designing of efficient strategies for breeding preharvest sprouting tolerant wheat.


Arabian killifish (Aphanius dispar) embryos: A model organism for the risk assessment of the Arabian Gulf coastal waters.
Fish embryos are excellent models for studies aimed at understanding toxic mechanisms and indications of possible acute and chronic effects. For the past 3 yr, an Arabian killifish (Aphanius dispar) fish embryo test has been developed in the authors' laboratory as a routine ecotoxicological test that can be used to support risk assessment of potential contaminants in Arabian Gulf coastal waters. Tests were conducted with 3 reference toxicants (3,4-dichloroaniline [DCA], sodium dodecyl sulfate, and zinc sulfate [Zn]) and chlorine, a disinfectant used widely in industrial cooling systems around the Arabian Gulf region. The 50% effect concentration (EC50) for DCA was 0.47 mg/L and 1.89 mg/L for embryos exposed before 6 hpf and after 168 hpf, respectively. Sublethal effects were mainly observed at concentrations above 2.5 mg/L, the effects included severe pericardial edema and tail shortage. The sodium dodecyl sulfate ionic surfactant caused mortality at both early and late stages of embryo development; it caused coagulation, severe deformity, and hemolysis. Both the EC50 and the 50% lethal concentration (LC50) for sodium dodecyl sulfate were 9.37 mg/L. Salinity influenced the toxicity of Zn to killifish embryos: at 40 psu Zn was found not to be toxic, whereas at 20 psu toxicity had increased significantly (p < 0.05). Values of EC50 and LC50 were 2.5 mg/L and 4 mg/L, respectively. Concentrations above 15 mg/L in embryos were often accompanied by upper abdominal edema and inhibition of growth, especially evident in the tail. Chlorine caused mortality at a lower concentration; for example, at 0.05 mg/L 33% of embryos were found dead at the end of the experiment. The LC50 for chlorine was determined to be 0.08 mg/L. Examination of the existing literature showed similar results to the present study's findings. The results suggest a more comparable sensitivity of killifish embryos to that of other fish embryo test recommended species. The present study's findings support the ability of killifish to be an indicator organism for environmental risk assessments of Arabian Gulf waters. Benefits include sensitivity to a wide range of substances and conditions, animal alternative, ease of fish breeding, and clarity of the embryos.


A semi-parametric estimate of extra-Poisson variation for vital rates.
We introduce a method for estimating overdispersion in Poisson models for vital rates. We assume smoothness conditions on the counts to obtain pointwise variance estimates that we combine to obtain an estimate of the overdispersion parameter. We create confidence intervals about the observed rates using this estimate and an approximation based on the gamma distribution. The advantage of this method is that the estimates of the superpopulation rates do not depend on the smoothness assumption, yet when this assumption is met we obtain approximately unbiased estimates of the overdispersion parameter. Thus, we may calculate confidence intervals for vital rates under an overdispersed Poisson model without making parametric assumptions on the mean rates.


Exercise training causes differential changes in gene expression in diaphragm arteries and 2A arterioles of obese rats.
We employed next-generation, transcriptome-wide RNA sequencing (RNA-Seq) technology to assess the effects of two different exercise training protocols on transcriptional profiles in diaphragm second-order arterioles (D2a) and in the diaphragm feed artery (DFA) from Otsuka Long Evans Tokushima Fatty (OLETF) rats. Arterioles were isolated from the diaphragm of OLETF rats that underwent an endurance exercise training program (EX; n = 13), interval sprint training program (SPRINT; n = 14), or remained sedentary (Sed; n = 12). Our hypothesis was that exercise training would have similar effects on gene expression in the diaphragm and soleus muscle arterioles because diaphragm blood flow increases during exercise to a similar extent as in soleus. Results reveal that several canonical pathways that were significantly altered by exercise in limb skeletal muscles were not among the pathways significantly changed in the diaphragm arterioles including actin cytoskeleton signaling, role of NFAT in regulation of immune response, protein kinase A signaling, and protein ubiquitination pathway. EX training altered the expression of a smaller number of genes than did SPRINT in the DFA but induced a larger number of genes with altered expression in the D2a than did SPRINT. In fact, FDR differential expression analysis (FDR, 10%) indicated that only two genes exhibited altered expression in D2a of SPRINT rats. Very few of the genes that exhibited altered expression in the DFA or D2a were also altered in limb muscle arterioles. Finally, results indicate that the 2a arterioles of soleus muscle (S2a) from endurance-trained animals and the DFA of SPRINT animals exhibited the largest number of genes with altered expression.


Small bowel endoluminal imaging (capsule and enteroscopy).
Over the last 16 years, the disruptive technologies of small bowel capsule endoscopy and device-assisted enteroscopy have revolutionised endoluminal imaging and minimally invasive therapy of the small bowel. Further technological developments continue to expand their indications and use. This brief review highlights the state-of-the-art in this arena and aims to summarise the current and potential future role of these technologies in clinical practice.


Hypometabolic and hypothermic factors from small intestine of hibernating ground squirrels (Citellus undulatus).
Low molecular mass components of the acetic acid extract from the small intestine of hibernating ground squirrels (Citellus undulatus) produced a decrease in oxygen consumption and body temperature of white mice and a dose-dependent delay in embryonic development of sea urchin (Strongylocentrotus intermedius). Equivalent doses of low molecular mass components obtained by the same method from active (summer) animals did not have such an effect.


Identification and analysis of the Arabidopsis thaliana BSH gene, a member of the SNF5 gene family.
The multiprotein complexes involved in active dis-ruption of chromatin structure, homologous to yeast SWI/SNF complex, have been described for human and Drosophila cells. In all SWI/SNF-class complexes characterised so far, one of the key components is the SNF5-type protein. Here we describe the isolation of a plant (Arabidopsis thaliana ) cDNA encoding a 27 kDa protein which we named BSH, with high homology to yeast SNF5p and its human (INI1) and Drosophila (SNR1) counterparts as well as to other putative SNF5-type proteins from Caenorhabditis elegans, fish and yeast. With 240 amino acids, the Arabidopsis BSH is the smallest SNF5-type protein so far identified. When expressed in Saccharomyces cerevisiae, the gene for BSH partially complements the snf5 mutation. BSH is, however, unable to activate transcription in yeast when tethered to DNA. The gene for BSH occurs in single copy in the Arabidopsis genome and is ubiquitously expressed in the plant. Analysis of the whole cell and nuclear protein extracts with antibodies against recombinant BSH indicates that the protein is localised in nuclei. Transgenic Arabidopsis plants with markedly decreased physiological level of the BSH mRNA, resulting from the expression of antisense messenger, are viable but exhibit a distinctive phenotype characterised by bushy growth and flowers that are unable to produce seeds.


Diversity of pufM genes, involved in aerobic anoxygenic photosynthesis, in the bacterial communities associated with colonial ascidians.
Ascidians are invertebrate filter feeders widely distributed in benthic marine environments. A total of 14 different ascidian species were collected from the Western Mediterranean and their bacterial communities were analyzed by denaturing gradient gel electrophoresis (DGGE) of 16S rRNA gene. Results showed that ascidian tissues harbored Bacteria belonging to Gamma- and Alphaproteobacteria classes, some of them phylogenetically related to known aerobic anoxygenic phototrophs (AAPs), such as Roseobacter sp. In addition, hierarchical cluster analysis of DGGE patterns showed a large variability in the bacterial diversity among the different ascidians analyzed, which indicates that they would harbor different bacterial communities. Furthermore, pufM genes, involved in aerobic anoxygenic photosynthesis in marine and freshwater systems, were widely detected within the ascidians analyzed, because nine out of 14 species had pufM genes inside their tissues. The pufM gene was only detected in those specimens that inhabited shallow waters (<77 m of depth). Most pufM gene sequences were very closely related to that of uncultured marine bacteria. Thus, our results suggest that the association of ascidians with bacteria related to AAPs could be a general phenomenon and that ascidian-associated microbiota could use the light that penetrates through the tunic tissue as an energy source.


Recent advances in the analysis of metal hyperaccumulation and hypertolerance in plants using proteomics.
Hyperaccumulator/hypertolerant plant species have evolved strategies allowing them to grow in metal-contaminated soils, where they accumulate high concentrations of heavy metals in their shoots without signs of toxicity. The mechanisms that allow enhanced metal uptake, root-to-shoot translocation and detoxification in these species are not fully understood. Complementary approaches such as transcriptomic-based DNA microarrays and proteomics have recently been used to gain insight into the molecular pathways evolved by metal hyperaccumulator/hypertolerant species. Proteomics has the advantage of focusing on the translated portion of the genome and it allows to analyze complex networks of proteins. This review discusses the recent analysis of metal hyperaccumulator/hypertolerant plant species using proteomics. Changes in photosynthetic proteins, sulfur, and glutathione metabolism, transport, biotic and xenobiotic defenses as well as the differential regulation of proteins involved in signaling and secondary metabolism are discussed in relation to metal hyperaccumulation. We also consider the potential contribution of several proteins to the hyperaccumulation phenotype.


Possible mechanism of the potent vasoconstrictor actions of ryanodine on femoral arteries from spontaneously hypertensive rats.
1. The Ca2+ buffering function of sarcoplasmic reticulum (SR) in the resting state of arteries from spontaneously hypertensive rats (SHR) was examined. Differences in the effects of ryanodine that removes the function of SR, on tension and cellular Ca2+ level were assessed in endothelium-denuded strips of femoral arteries from 13-week-old SHR and normotensive Wistar-Kyoto rats (WKY). 2. The addition of ryanodine to the resting strips caused a concentration-dependent contraction in SHR. This contraction was extremely small in WKY. In the presence of 10(-5) M ryanodine, caffeine (20 mM) failed to cause a further contraction in SHR, but it caused a small contraction in WKY. After washout of the strips with a Krebs solution, the resting tone was greatly elevated in SHR when compared with WKY. 3. The elevated resting tone in SHR strips was abolished by 10(-7) M nifedipine. The ryanodine-induced contraction was also abolished by 10(-7) M nifedipine. Nifedipine itself caused a relaxation from the resting tone of SHR strips, suggesting the maintenance of myogenic tone. 4. In strips preloaded with fura-PE3, the addition of 10(-5) M ryanodine caused a large and moderate elevation of cytosolic Ca2+ level ([Ca2+]i) in SHR and WKY, respectively. After washout, the resting [Ca2+]i was greatly elevated in SHR. The ryanodine-induced elevation of [Ca2+]i was decreased by 5 x 10(-6) M verapamil in SHR. Verapamil itself caused a decrease in resting [Ca2+]i which was significantly greater in SHR than in WKY, and caused a relaxation only in SHR. 5. The resting Ca2+ influx in arteries measured by a 5 min incubation with 45Ca was significantly increased in SHR when compared with WKY. The resting Ca2+ influx was not increased by 10(-5) M ryanodine in both SHR and WKY. The net cellular Ca2+ uptake in arteries measured by a 30 min incubation with 45Ca was decreased by 10(-5) M ryanodine in both strains. 6. The resting Ca2+ influx was decreased by 10(-7) M nifedipine in the SHR artery, but it was unchanged in the WKY artery. 7. These results suggest that (1) the Ca2+ influx via L-type voltage-dependent Ca2+ channels was increased in the resting state of the SHR femoral artery, (2) the greater part of the increased Ca2+ influx was buffered by Ca2+ uptake into the SR and some Ca2+ reached the myofilaments resulting in the maintenance of the myogenic tone, and (3) therefore the functional removal of SR by ryanodine caused a potent contraction in this artery.


Autologous fat injection for vocal cord medialization in the canine larynx.
This study examined the use of autologous fat as an alternative to Teflon and collagen as the implantable material in vocal cord medialization. Five animals underwent left recurrent laryngeal nerve sections with subsequent fat harvest and implantation into the left true vocal cords. Three animals were killed after 48 hours and 2 after 3 weeks; their larynges were examined with light microscopy. The results of the 48-hour samples show mode-rate acute inflammation and few areas of focal necrosis. The 3-week samples show no necrotic foci, minimal foreign-body reaction, and maintenance of structure and volume of the injected fat. Autologous fat may prove to be a valuable alternative to nonautologous injectable material in vocal cord augmentation.


What Is the Difference in Cranial Base Morphology in Isolated and Syndromic Bicoronal Synostosis?
The association of isolated craniosynostosis and the influence of syndromic forms confound the understanding of craniofacial morphologic development. This study attempts to clarify the individual influences of isolated bicoronal synostosis, Apert syndrome, and Crouzon syndromes on skull base morphology. One hundred seventeen computed tomographic scans were included (nonsyndromic bicoronal synostosis, n = 36; Apert syndrome with bicoronal synostosis, n = 25; Crouzon syndrome with bicoronal synostosis, n = 11; controls, n = 45). Cephalometric measurements were analyzed using Materialise software. Nonsyndromic bicoronal synostosis patients developed a shortened cranial base length, with a significantly shortened distance between nasion and sella (p = 0.005). The cranial base angles of nonsyndromic bicoronal synostosis in both the cranial side (N-S-BA) and facial side (N-SO-BA) increased significantly, by 17.04 degrees (p < 0.001) and 11.75 degrees (p < 0.001), respectively. However, both the N-S-BA and N-SO-BA angles of Apert syndrome and Crouzon syndrome were narrowed more than that of nonsyndromic bicoronal synostosis [by 12.11 degrees (p < 0.001) and 12.44 degrees (p < 0.001), respectively, in Apert syndrome; and by 11.66 degrees (p = 0.007) and 13.71 degrees (p = 0.007), respectively, in Crouzon syndrome]. However, there is no statistically significant difference of these two angles between Apert syndrome and Crouzon syndrome, when they were only associated with bicoronal synostosis. Contrary to the relatively normal subcranial space of nonsyndromic bicoronal synostosis, both Apert and Crouzon syndromes developed a reduced subcranial space. Isolated bicoronal synostosis resulted in a flattened cranial base, whereas Apert syndrome and Crouzon syndrome developed a normal cranial base angle when only associated with bicoronal synostosis. The syndromic skulls had additional significantly reduced subcranial space.


Score of neonatal acute physiology as a measure of illness severity in mechanically ventilated term babies.
The objectives of this population-based, case-control cohort study were to describe the use of the score of neonatal acute physiology (SNAP) as a measure of illness severity in mechanically ventilated term infants, to compare the SNAP scores of the different diagnostic groups, to assess the contribution of the individual SNAP items to the overall SNAP severity category, and to assess SNAP as a predictor of mortality and neonatal intensive care unit (NICU) resource utilization (length of stay (LOS) and duration of ventilation (LOV)). The study was carried out in Sydney and four large rural/urban health areas in New South Wales, Australia. The subjects--182 singleton term infants with no major congenital anomalies--were admitted to a tertiary NICU for mechanical ventilation. Highest mean (SD) SNAP scores occurred in infants ventilated for meconium aspiration (18 (9)), and perinatal asphyxia (17 (9)), compared with pulmonary hypertension (14 (6)) and respiratory distress syndrome (13 (5)). The individual SNAP items that contributed most to SNAP moderate and severe categories were blood gas items, creatinine, urine output, blood glucose, and seizures. Predictors of death included total SNAP score, individual SNAP items (urine output, pH, Oxygenation Index (OI)), 5-min Apgar, gestational age >40 wk, growth restriction, and ventilation for asphyxia/apnoea. SNAP alone was not a good predictor of NICU resource utilization (LOS, LOV) in term infants. The best predictors were LOV for LOS, and a combination of SNAP and the reason for ventilation for LOV. SNAP is a useful measure of severity of illness in sick term neonates admitted to a tertiary NICU. This measure can be used to predict neonatal morbidity and mortality, and to some extent NICU resource utililization.


A broadly active viral inhibitor in human and animal organ extracts and body fluids.
To help assess the possibility that a newly described viral inhibitor from cell cultures might play a natural defensive role in vivo, its distribution and concentration in human and animal organ extracts and body fluids were investigated. The concentration of the inhibitor was high in human liver, heart muscle, splenic extracts, and human serum and milk. The inhibitor in the body was indistinguishable from a previously described inhibitor produced in cell cultures that was characterized by broad antiviral activity, lack of target cell species specificity, lack of induction of stable antiviral activity in cells, rapid reversibility of antiviral action, prevention of virus attachment, and stability at 100 degrees C. Sixteen virus plaque reduction units of the inhibitor diminished the yield of poliovirus in vitro by more than 1000-fold. Additional evidence that contact-blocking viral inhibitor (CVI) inhibits vaccinia virus attachment to cells is presented. A role for the inhibitor in natural defense against viral infections is possible.


Socioeconomic and Demographic Factors Influencing Women's Attitude Toward Wife Beating in Ethiopia.
This study used data from the Ethiopian Demographic and Health Survey (EDHS) for a total of 42,054 women (15-49 years) from Ethiopia's 11 geographic/administrative regions using a stratified, two-stage cluster sample design to reflect the country's huge geographical, cultural, ethnic, and linguistic diversity. The study first identified the major socioeconomic and demographic factors influencing women's attitude toward wife beating in Ethiopia, and then provided some suggestions on what types of interventions are required to address the problems. Toward this effect, female participants were asked whether a husband is justified in beating his wife under five possible circumstances. Ironically, the majority of women support wife beating if a wife goes out without telling a husband (51.8%), neglects her children (58.1%), argues with a husband (53.4%), refuses to have sex with a husband (47.9%), and burns food while preparing meals (53.3%). The study also used the probit regression model and identified the following factors influencing women's attitude toward wife beating in Ethiopia: women's economic status, women's level of education, husband's level of education, access to media, marital status, place of residence (urban vs. rural), and women's awareness about the law against wife beating. The way forward will require the empowerment of women through education and training, an increase in women's access to resources, strong legislation against domestic violence, and creating awareness among community and religious leaders. As the best way to end intimate partner violence against women is to prevent it from happening in the first place by addressing its main causes, this study is thus of paramount importance for the overall efforts in raising awareness to prevent such violence against women.


Detection and Characterization of TiO2 Nanomaterials in Sludge from Wastewater Treatment Plants of Chihuahua State, Mexico.
TiO2 nanoparticles (TiO2-NPs) have a wide range of industrial applications (paintings, sunscreens, food and cosmetics) and is one of the most intensively used nanomaterials worldwide. Leaching from commercial products TiO2-NPs are predicted to significantly accumulate in wastewater sludges, which are then often used as soil amendment. In this work, sludge samples from four wastewater treatment plants of the Chihuahua State in Mexico were obtained during spring and summer (2017). A comprehensive characterization study was performed by X-ray based (laboratory and synchrotron) techniques and electron microscopy. Ti was detected in all sludge samples (1810-2760 mg/kg) mainly as TiO2 particles ranging from 40 nm up to hundreds of nm. Micro-XANES data was analyzed by principal component analysis and linear combination fitting enabling the identification of three predominant Ti species: anatase, rutile and ilmenite. Micro-XANES from the smaller Ti particles was predominantly anatase (68% + 32% rutile), suggesting these TiO2-NPs originate from paintings and cosmetics. TEM imaging confirmed the presence of nanoscale Ti with smooth surface morphologies resembling engineered TiO2-NPs. The size and crystalline phase of TiO2-NPs in the sludge from this region suggest increased reactivity and potential toxicity to agro-systems. Further studies should be dedicated to evaluating this.


Anatomical Study of the Fingertip Artery in Tamai Zone I: Clinical Significance in Fingertip Replantation.
Background There are a few previous studies of the vascular anatomy of the fingertips. The aim of this study was to evaluate this anatomy and the distribution of fingertip arteries. Patients and Methods A total of 31 cadaveric hands were used for evaluation of the vascular pattern of the fingertips on X-ray images obtained using a radiopaque material. We analyze the anatomy of the fingertip arteries, and classified it into three types in Tamai zone I. If only one dominant artery branched off from the distal transverse palmar arch, it was classified as type I. If the fingertip had branches of two dominant arteries, it was classified as type II, and if the fingertip had branches of three or more dominant arteries, it was classified as type III. Results The incidence of type I was 27%, that of type II was 28%, and the incidence of type III was 45%, the latter being the most frequent. In addition, we analyzed the pattern in each finger. The frequency of type III decreased from the index finger to the little finger, and the frequencies of types I and II increased from the index finger to the little finger. Conclusion Type III was the most common type in fingers, and its frequency decreased from the index finger to the little finger.


Substrate kinetics of the tonoplast h-translocating inorganic pyrophosphatase and its activation by free mg.
To clarify the kinetic characteristics and ionic requirements of the tonoplast H(+)-translocating inorganic pyrophosphatase (H(+)-PPiase), PPi hydrolysis and PPi-dependent H(+) transport were studied in tonoplast vesicles isolated from leaf mesophyll tissue of Kalanchoë daigremontiana Hamet et Perrier de la Bâthie. The tonoplast H(+)-PPiase showed an absolute requirement for a monovalent cation and exhibited hyperbolic kinetics with respect to cation concentration. H(+)-PPiase activity was maximal in the presence of K(+) (K(50) approximately 3 millimolar), with PPi-dependent H(+) transport being more selective for K(+) than PPi hydrolysis. When assayed in the presence of 50 millimolar KCl at fixed PPi concentrations, H(+)-PPiase activity showed sigmoidal kinetics with respect to total Mg concentration, reflecting a requirement for a Mg/PPi complex as substrate and free Mg(2+) for activation. At saturating concentrations of free Mg(2+), H(+)-PPiase activity exhibited Michaelis-Menten kinetics towards MgPPi(2-) but not Mg(2)PPi, demonstrating that MgPPi(2-) was the true substrate of the enzyme. The apparent K(m) (MgPPi(2-)) for PPi hydrolysis (17 micromolar) was significantly higher than that for PPi-dependent H(+) transport (7 micromolar). Free Mg(2+) was shown to be an allosteric activator of the H(+)-PPiase, with Hill coefficients of 2.5 for PPi hydrolysis and 2.7 for PPi-dependent H(+) transport. Half-maximal H(+)-PPiase activity occurred at a free Mg(2+) concentration of 1.1 millimolar, which lies within the range of accepted values for cytosolic Mg(2+). In contrast, cytosolic concentrations of K(+) and MgPPi(2-) appear to be saturating for H(+)-PPiase activity. We propose that one function of the H(+)-PPiase may be to act as an ancillary enzyme that maintains the proton-motive force across the vacuolar membrane when the activity of the tonoplast H(+)-ATPase is restricted by substrate availability. As ATP levels decline in the cytosol, free Mg(2+) would be released from the MgATP(2-) complex, thereby activating the tonoplast H(+)-PPiase.


Infanticide in chimpanzees: Taphonomic case studies from Gombe.
We present a study of skeletal damage to four chimpanzee (Pan troglodytes) infanticide victims from Gombe National Park, Tanzania. Skeletal analysis may provide insight into the adaptive significance of infanticide by examining whether nutritional benefits sufficiently explain infanticidal behavior. The nutritional hypothesis would be supported if bone survivorship rates and skeletal damage patterns are comparable to those of monkey prey. If not, other explanations, such as the resource competition hypothesis, should be considered. Taphonomic assessment of two chimpanzee infants included description of breakage and surface modification, data on MNE, %MNE, and bone survivorship. Two additional infants were assessed qualitatively. The data were compared to published information on monkey prey. We also undertook a review of published infanticide cases. The cases were intercommunity infanticides (one male and three female infants) committed by males. Attackers partially consumed two of the victims. Damage to all four infants included puncture marks and compression fractures to the cranium, crenulated breaks to long bones, and incipient fractures on ribs. Compared to monkey prey, the chimpanzee infants had an abundance of vertebrae and hand/foot bones. The cases described here suggest that chimpanzees may not always completely consume infanticide victims, while reports on chimpanzee predation indicated that complete consumption of monkey prey usually occurred. Infanticidal chimpanzees undoubtedly gain nutritional benefits when they consume dead infants, but this benefit may not sufficiently explain infanticide in this species. Continued study of infanticidal and hunting behavior, including skeletal analysis, is likely to be of interest.


HIV testing implementation in two urban cities: practice, policy, and perceived barriers.
Although funding has supported the scale up of routine, opt-out HIV testing in the US, variance in implementation mechanisms and barriers in high-burden jurisdictions remains unknown. We conducted a survey of health care organizations in Washington, DC and Houston/Harris County to determine number of HIV tests completed in 2011, policy and practices associated with HIV testing, funding mechanisms, and reported barriers to testing in each jurisdiction and to compare results between jurisdictions. In 2012, 43 Houston and 35 DC HIV-testing organizations participated in the survey. Participants represented 85% of Department of Health-supported testers in DC and 90% of Department of Health-supported testers in Houston. The median number of tests per organization was 568 in DC and 1045 in Houston. Approximately 50% of organizations in both DC and Houston exclusively used opt-in consent and most conducted both pre- and post-test counseling with HIV testing (80% of organizations in DC, 70% in Houston). While the most frequent source of funding in DC was the Department of Health, Houston organizations primarily billed the patient or third-party payers. Barriers to testing most often reported were lack of funding, followed by patient discomfort/refusal with more barriers reported in DC. Given unique policies, resources and programmatic contexts, DC and Houston have taken different approaches to support routine testing. Many organizations in both cities reported opt-in consent approaches and pre-test counseling, suggesting 2006 national HIV testing recommendations are not being followed consistently. Addressing the barriers to testing identified in each jurisdiction may improve expansion of testing.


Collaboration to promote best practices in care of older adults.
A successful grassroots collaboration of faculty members from one Midwestern school of nursing to promote best practices in gerontological nursing is described. Recommendations are made for developing similar collaborations in other settings.


Management of asthma and COPD patients: feasibility of the application of guidelines in general practice.
To examine the feasibility of the application of guidelines to the management of asthma and chronic obstructive pulmonary disease (COPD) by assessing compliance with the guidelines and listing the barriers general practitioners (GPs) encountered during implementation. Insight into the feasibility of individual items in the guidelines can guide implementation strategies in the future and, if necessary, support revision of the guidelines. Descriptive study of care delivered during the implementation of guidelines by means of documentation of the care provided, education, feedback on compliance and peer review. General practice. Sixteen GPs in 14 general practices. Compliance was expressed as the percentage of patients per practice managed by the GPs according to the guidelines. For each patient (n=413) data were collected on the care delivered during the first year of the implementation. Barriers encountered were derived from the summaries of the discussions held during the monthly meetings. The GPs were most compliant on the items 'PEFR measurement at every consultation' (98%), 'allergy test' (78%) and 'advice to stop smoking' (82%), and less compliant on the items 'four or more consultations a year' (46%), 'ordering spirometry' (33%), 'adjustment of medication' (42%), 'check on inhalation technique' (38%) and referral to a chest physician (17%) or a district nurse (5%). The main barriers were the amount of time to be invested, doubts about the necessity of regular consultations and about the indications for ordering spirometry and for referral to a chest physician or a district nurse. Although the feasibility was assessed in a fairly optimal situation, compliance with the guidelines was not maximal, and differed between the individual items of care. Suggestions are given for further improvements in compliance with the guidelines and for revision of the guidelines.


Soil-geomorphic heterogeneity governs patchy vegetation dynamics at an arid ecotone.
Soil properties are well known to affect vegetation, but the role of soil heterogeneity in the patterning of vegetation dynamics is poorly documented. We asked whether the location of an ecotone separating grass-dominated and sparsely vegetated areas reflected only historical variation in degradation or was related to variation in inherent soil properties. We then asked whether changes in the cover and spatial organization of vegetated and bare patches assessed using repeat aerial photography reflected self-organizing dynamics unrelated to soil variation or the stable patterning of soil variation. We found that the present-day ecotone was related to a shift from more weakly to more strongly developed soils. Parts of the ecotone were stable over a 60-year period, but shifts between bare and vegetated states, as well as persistently vegetated and bare states, occurred largely in small (<40 m2) patches throughout the study area. The probability that patches were presently vegetated or bare, as well as the probability that vegetation persisted and/or established over the 60-year period, was negatively related to surface calcium carbonate and positively related to subsurface clay content. Thus, only a fraction of the landscape was susceptible to vegetation change, and the sparsely vegetated area probably featured a higher frequency of susceptible soil patches. Patch dynamics and self-organizing processes can be constrained by subtle (and often unrecognized) soil heterogeneity.


Time-resolved identification of modes and measurement of intermodal dispersion in optical fibers.
Picosecond pulses from a tunable mode-locked visible dye laser are injected into a 603-m few-mode optical fiber. Measurements of the output power temporal profile with 35-ps resolution show six clearly resolved modes. Time-profile measurements over a two-dimensional array of points in the fiber output far field yield a picture of each mode that identifies it. Measurements as a function of wavelength and fitting to waveguide dispersion calculations are used to model the fiber core refractive-index profile. As a result for the nominal step-index fiber used in this work, the presence of an index dip at the center of the core was detected.


Measurement of surface acoustic waves in high-frequency ultrasound: Preliminary results.
Skin lesions change elastic properties near the surface. In the last decades, several non-invasive elastography techniques have been developed for detecting the mechanical properties of tissue. In particular, harmonic elastography is characterized for inducing shear wave propagation by an external vibrator in order to estimate shear modulus. However, near the boundary region, propagation is governed by surface acoustic waves (SAW). This paper combines crawling waves elastography with a high-frequency ultrasound (HFUS) system for the estimation of the SAW-to-shear compensation factor when ultrasound (US) gel is used as coupling interface. Experiments explore the SAWspeed in a homogeneous phantom with a solid-water interface in order to corroborate theoretical findings. Subsequently, experiments in a solid-US gel interface are conducted in order to find the correct compensation factor. Preliminary results suggest that SAW propagation can be detected using HFUS, and shear velocity maps can be generated by applying the estimated empirical correction factor. This study will potentially avoid the underestimation of shear modulus when using SAW-based HFUS elastography which is promising for the better diagnosis of skin diseases.


Regular physical activity and reduced occurrence of microalbuminuria in type 2 diabetic patients.
In order to evaluate the influence of regular non-strenuous physical exercise on the appearance of microalbuminuria in Type 2 (non-insulin-dependent) diabetic patients, we have studied a cohort of 372 Type 2 diabetic patients (152 males and 220 females, mean age: 63.59 +/- 0.70 years, evolution time: 10.31 +/- 0.4 years, M +/- SEM). One hundred and ninety seven (52.9%) presented normo-albuminuria, 124 (33.3%) microalbuminuria and 51 (13.7%) proteinuria. These three groups were different with regard to evolution time, weight, BMI, waist-hip ratio, Hb1Ac value, prevalence of hypertension and physical activity level. 132 (35.4%) patients had a regular exercise-induced caloric expenditure under 500 kcal/wk whereas 122 (32.7%) were between 500 and 1.000 kcal/wk and 118 (31.7%) over 1.000 kcal/wk. Prevalence of normo-albuminuric patients was 40.1%, 52.4% and 67.7% respectively (p < 0.01). Prevalence of normo-albuminuric patients remained significatively higher in the patient with the greater physical activity level when adjusted to systolic blood pressure, diastolic blood pressure, evolution time and HbA1c value. Our results stress the fact that regular non-strenuous physical activity may have a protective effect on the appearance of microalbuminuria in Type 2 (non-insulin-dependent) diabetic patients. Whether the cardiovascular protective influence of exercise in these patients depends on such an effect remains unknown. On the basis of this cross-sectional evidence, a longitudinal study is now under way.


STRAP as a New Therapeutic Target for Poor Prognosis of Pancreatic Ductal Adenocarcinoma Patients Mainly Caused by TP53 Mutation.
Pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate and poor prognosis. KRAS, TP53, CDKN2A, and SMAD4 are driver genes of PDAC and 30-75% patients have mutations in at least two of these four genes. Herein, we analyzed the relationship between these genes and prognosis of 762 patients in the absence of coexisting mutations, using data from three independent public datasets. Interestingly, we found that compared with mutations in other driver genes, TP53 mutation plays a significant role in leading to poor prognosis of PDAC. Additionally, we found that snoRNA-mediated rRNA maturation was responsible for the progression of cancer in PDAC patients with TP53 mutations. Inhibition of STRAP, which regulates the localization of SMN complexes and further affects the assembly of snoRNP, can effectively reduce maturation of rRNA and significantly suppress progression of TP53-mutant or low p53 expression pancreatic cancer cells in vitro and in vivo. Our study highlighted the actual contribution rate of driver genes to patient prognosis, enriching traditional understanding of the relationship between these genes and PDAC. We also provided a possible mechanism and a new target to combat progression of TP53-mutant PDAC patients.


Expression of PPAR and RXR isoforms in the developing rat and human term placentas.
Placental fatty acid transfer is critical to meet the foetal requirements necessary for the biosynthesis of biological membranes, myelin, and various signaling molecules. The primary objective of this research was to elucidate the placental expression patterns of genes that may potentially regulate placental fatty acid transfer and homeostasis. In this study, we have elucidated the temporal and spatial patterns of expression of peroxisome proliferator-activated receptor (PPAR) and 9-cis retinoic acid receptor (RXR) isoforms in the junctional and labyrinth zones of the developing rat chorioallantoic placenta and in human term placenta. PPAR (alpha, beta, and gamma) and RXR (alpha, beta, and gamma) isoforms are nuclear hormone receptors that are known to regulate gene transcription and protein expression levels of fatty acid transport and metabolism mediating proteins through the formation of a DNA binding heterodimer complex. In the present study, the expression patterns of PPAR and RXR isoforms were determined in developing rat placenta and human term placenta using RT-PCR and immunohistochemical analyses. PPARalpha, beta, gamma, RXRalpha, beta and gamma were expressed in both junctional (invasive/endocrine function) and labyrinth (transport barrier) zones of the rat placenta, from day 13 to day 21 of gestation. In the human term placenta, PPARalpha, beta, gamma, RXRalpha and gamma were observed, while RXRbeta was not detected. Immunocytochemistry staining results determined the presence of PPARalpha, beta, gamma, RXRalpha and gamma to be specific to the syncytial trophoblast layer of the human chorionic villi. The presence of PPAR and RXR isoforms in both the rat and human placentas suggest that PPAR and RXR isoforms are potential regulators of placental lipid transfer and homeostasis. Our work provides a framework for the further investigation of PPAR and RXR isoform specific regulation of placental fatty acid uptake, transport and metabolism.


Progesterone-Related Immune Modulation of Pregnancy and Labor.
Pregnancy involves a complex interplay between maternal neuroendocrine and immunological systems in order to establish and sustain a growing fetus. It is thought that the uterus at pregnancy transitions from quiescent to laboring state in response to interactions between maternal and fetal systems at least partly via altered neuroendocrine signaling. Progesterone (P4) is a vital hormone in maternal reproductive tissues and immune cells during pregnancy. As such, P4 is widely used in clinical interventions to improve the chance of embryo implantation, as well as reduce the risk of miscarriage and premature labor. Here we review research to date that focus on the pathways through which P4 mediates its actions on both the maternal reproductive and immune system. We will dissect the role of P4 as a modulator of inflammation, both systemic and intrinsic to the uterus, during human pregnancy and labor.


Advanced Cambrian hydroid fossils (Cnidaria: Hydrozoa) extend the medusozoan evolutionary history.
Primitive cnidarians are crucial for elucidating the early evolution of metazoan body plans and life histories in the late Neoproterozoic and Palaeozoic. The highest complexity of both evolutionary aspects within cnidarians is found in extant hydrozoans. Many colonial hydrozoans coated with chitinous exoskeletons have the potential to form fossils; however, only a few fossils possibly representing hydroids have been reported, which still require scrutiny. Here, we present an exceptionally well-preserved hydroid found in the Upper Cambrian Fengshan Formation in northern China. It was originally interpreted as a problematic graptolite with an uncertain systematic position. Based on three characteristic morphological traits shared with extant hydroids (with paired hydrothecae, regular hydrocaulus internodes and special intrathecal origin pattern of hydrocladium), we propose this fossil hydroid as a new genus, Palaeodiphasia gen. nov., affiliated with the advanced monophyletic hydrozoan clade Macrocolonia typically showing loss of the medusa stage. More Macrocolonia fossils reviewed here indicate that this life strategy of medusa loss has been achieved already as early as the Middle Devonian. The early stratigraphical appearance of such advanced hydroid contrasts with previous molecular hypotheses regarding the timing of medusozoan evolution, and may be indicative for understanding the Ediacaran cnidarian radiation.


Molecular heterogeneity of triple-negative breast cancer and its clinical implications.
Triple-negative breast cancer (TNBC) is defined by a lack of expression of hormone receptors, oestrogen and progesterone, as well as human epidermal factor receptor 2. This review focuses on the increasing understanding of the molecular heterogeneity of TNBC subtypes and the therapeutic implications of this subclassification. Emerging evidence clearly indicates that TNBC is a heterogeneous disease with varying prognosis according to clinical, pathological and genetic factors. Some distinct histological special types within this clinically defined collection of entities have been shown to have a particularly good prognosis (e.g. medullary carcinomas), and others very poor outcome (e.g. metaplastic carcinomas), whereas the broader immunohistochemically defined 'core-basal-like' or gene expression defined 'basal' groups generally have a poor prognosis. This molecular subclassification has implicated several biological processes as potential therapeutic targets: the DNA damage response, drivers of deregulated proliferation, angiogenesis, epithelial-mesenchymal transition and immune deregulation. Molecular stratification of these prognostic groups has been critical in identifying novel therapeutic targets for future drug development. The development of poly-(ADP)ribose polymerase inhibitors for BRCA1-mutation carriers with TNBC has led the ongoing efforts to translate fundamental biological insights into improved therapies for a difficult-to-treat breast cancer subgroup.


New, male-specific microsatellite markers from the human Y chromosome.
Seven novel microsatellite markers have been developed from a new cosmid library constructed from flow-sorted human Y chromosomes. These microsatellites are tetranucleotide GATA repeats and are polymorphic among unrelated individuals. Five of the seven markers are male-specific, with no PCR product being generated from female DNA. One marker produces male-specific, polymorphic PCR products but occasionally produces a much larger, invariant product from female DNA. The remaining marker is polymorphic in both males and females with many shared alleles between the sexes. This report of six new, male-specific markers doubles the number of tetranucleotide markers that are currently available for the human Y chromosome. These new markers will be valuable where nonrecombining, gender-specific DNA markers are desired, including forensic investigations as well as studies of populations and their evolutionary histories.


Lack of modifying effects of prepubertal exposure to acrylamide (AA) on N-methyl-N-nitrosourea (MNU)-induced multi-organ carcinogenesis in F344 rats.
Acrylamide (AA) has been reported to be formed in fried and baked foods with various concentrations, and exposure levels to AA from cooked foods in children are estimated to be higher than those in adults. In order to evaluate the carcinogenicity of AA exposure during childhood, we conducted a medium-term carcinogenicity study with prepubertal administration of AA followed by treatments of a multi-organ-targeted genotoxic carcinogen and a promoting agent for thyroid carcinogenesis in rats. A total of 36 postpartum F344 rats were given drinking water containing AA at 0, 20, 40 or 80 ppm for 3 weeks during the lactation period, and their weaned offspring received the same AA-containing water for 3 more weeks. Offspring were then injected with N-methyl-N-nitrosourea (MNU; 40 mg/kg body weight, i.p.) once at week 7 after birth. Half the animals of the 0 and 40 ppm groups were additionally treated with the anti-thyroid agent sulfadimethoxine (SDM; 125 ppm) in the drinking water thereafter. Offspring were subjected to complete necropsy at week 50. All the major organs and macroscopic abnormalities were excised and examined histopathologically. There was no significant difference in the incidences of hyperplastic and neoplastic lesions in the target organs of AA and/or MNU, such as the brain, spinal cord, pituitary gland, thyroid, adrenal glands, uterus, mammary glands, clitoral gland and tunica vaginalis. In conclusion, no significant modifying actions of AA on MNU-induced multi-organ carcinogenesis were exhibited in any organs of rats when exposed prepubertally under the present experimental conditions.


Simultaneous Determination of Linear and Nonlinear Electrophoretic Mobilities of Cells and Microparticles.
Direct-current insulator-based electrokinetics (DC-iEK) is a branch of microfluidics that has demonstrated to be an attractive and efficient technique for manipulating micro- and nano- particles, including microorganisms. A unique feature of DC-iEK devices is that nonlinear EK effects are enhanced by the presence of regions of higher field intensity between the insulating structures. Accurate computational models, describing particle and cell behavior, are crucial to optimize the design and improve the performance of DC-iEK devices. The electrokinetic equilibrium condition (EEEC) is a recently introduced fundamental concept that has radically shifted the perspective behind the analysis of particle manipulation in these microfluidic devices. The EEEC takes into consideration previously neglected nonlinear effects on particle migration and indicates that these effects are central to control particle motion in DC-iEK devices. In this study, we present a simultaneous experimental characterization of linear and nonlinear electrokinetic (EK) parameters, that is, the electrophoretic mobility (μEP(1)), the particle zeta potential (ζP), the EEEC, and the electrophoretic mobility of the second kind (μEP(3)), for four types of polystyrene microparticles and four cell strains. For this, we studied the electromigration of polystyrene microparticles ranging in size from 2 to 6.8 μm, three bacteria strains (B. cereus, E. coli, and S. enterica) and a yeast cell (S. cerevisiae), ranging in size from 1 to 6.3 μm, in a polydimethylsiloxane (PDMS) microfluidic channel with a rectangular cross-section. The results illustrated that electrokinetic particle trapping can occur by linear and nonlinear electrophoresis and electroosmosis reaching an equilibrium, without the presence of insulating posts. The experimentally measured parameters reported herein will allow optimizing the design of future DC-iEK devices for a wide range of applications (e.g., to separate multiple kinds of particles and microorganisms) and for developing computational models that better represent reality.


Antiadhesion and anti-inflammation effects of noni (Morinda citrifolia) fruit extracts on AGS cells during Helicobacter pylori infection.
Helicobacter pylori is a human gastric pathogen that adheres to host cells and injects cytotoxin-associated gene A (CagA) to induce interleukin-8 (IL-8), inducible nitric oxide (iNOS), and cyclooxygenase 2 (COX-2). Noni (Morinda citrifolia) is found to possess antibacteria, anti-inflammation, and antioxidation activities, but its effect on H. pylori infection is still unknown. Ethanol and ethyl acetate extracts of noni fruit were used in this study. The inhibitory effect on CagA and H. pylori-induced IL-8, iNOS, and COX-2 were determined. The coculture medium was collected for measuring neutrophil chemotaxis. Both extracts of noni fruit showed weak inhibition on H. pylori. Both ethanol and ethyl acetate extracts provided antiadhesion of H. pylori to AGS cells and down-regulation on the CagA, IL-8, COX-2, and iNOS expressions. Results also indicated both extracts relieved neutrophil chemotaxis. Noni fruit extracts down-regulated inflammatory responses during H. pylori infection, and the phenolic compounds play key role in antiadhesion.


Unverricht-Lundborg disease, a condition with self-limited progression: long-term follow-up of 20 patients.
To assess the long-term evolution of Unverricht-Lundborg disease (ULD), especially concerning myoclonus, seizures, and EEG characteristics. We retrospectively evaluated 20 patients (six women, 14 men; mean age, 37.9 years; range, 26-53 years) with ULD who had been closely followed up since the onset of the disease (mean age, 12.3 years; range, 6-17 years) for an average of 25.6 years (range, 13-41 years). ULD was confirmed by genetic tests in all. We used simplified myoclonus and seizure rating scales. The geographic origin of the patients was Northern Africa in nine, France in two, Italy in six, and mixed European in three. Three patients were severely handicapped, six led fully autonomous lives, and 11 required various degrees of social support. Myoclonus progressed only during the first 5 years of disease. Major seizures occurred in 19. Three patients had a single seizure, and eight became seizure free, whereas six had rare seizures, and two had frequent attacks. Overall, seizures became much less frequent after 10 years of evolution. EEG changes abated during follow-up: background activity remained stable or improved, spontaneous discharges disappeared, and photoparoxysmal responses were abolished in all patients but two. This study shows that ULD progresses only over a limited period and stabilizes thereafter. This self-limited progression may be the consequence of age-related apoptosis of selected neuronal populations.


Treatment of Different Oral Soft Tissue Lesions With Surgical Neodymium: Yttrium-Aluminum-Garnet Laser: Case Series.
Oral soft tissue lesions cause discomfort and potentially serious clinical problems. These case reports present different gingival and/or mucosal lesions (pyogenic granuloma, verruca vulgaris, giant cell granuloma, fibroma, etc.) and the surgical treatment of these lesions with a neodymium:yttrium-aluminum-garnet (Nd:YAG) laser (320-μm optic fiber; 4 W; 100 mJ, 40 Hz; emission mode, pulsed, and contact mode). Patients were evaluated after laser surgery on degree of postoperative pain; discomfort; functional complications (eating and speech); and recurrence. Results indicated that patients had minimal postoperative pain, few functional complications, and low rates of pain. Laser surgery produced minimal bleeding, damage to the surrounding tissue, and post-surgical edema. In these cases, the Nd:YAG laser provided a non-bleeding environment at the surgical area with an acceptable operating time, quick postoperative hemostasis, good patient acceptance, low rates of pain, and no post-treatment adverse events among patients with oral soft tissue lesions.


Leukotrienes: Novel targets for vascular disease.
Extract: Atherosclerosis is a chronic disease of the large arteries and the primary cause of heart attacks and stroke. It is a major cause of morbidity and mortality in the Western world and accounts for 50% of all deaths. According to a recent Center for Disease Control and Prevention (CDC, Atlanta, GA) survey, atherosclerosis has now become the single largest cause of death worldwide at 33%, replacing infectious diseases as the developing countries become more prosperous. Among the many risk factors, increased serum cholesterol carried by low-density lipoproteins (LDL), especially in oxidized LDL, is the single greatest contributing factor in the development of the disease. However, atherosclerosis is now recognized as an inflammatory vascular disease, but the molecular events involved in the initiation and development of the disease are still largely unknown. Recruitment of monocytes to specific sites in the arterial wall may be the initiating step, followed by the uptake of oxidized LDL by these monocytes, leading to their conversion into lipid-laden foam cells.


Kinetics of tyrosyl radical reduction by selenocysteine.
The rate constant for the reduction of the tyrosyl radical with selenocysteine has been measured to investigate whether selenocysteine is capable of repair of protein radicals. Tyrosyl radicals, both free in solution and in insulin, were generated by means of pulse radiolysis and laser flash photolysis in aqueous solution. The rate constant for the reaction of free N-acetyl-tyrosyl-amine radicals with selenocysteine is (8 +/- 2) x 10 (8) M (-1) s (-1), and that for tyrosyl radicals in insulin is (1.6 +/- 0.4) x 10 (8) M (-1) s (-1). The rate constant for the reaction of selenoglutathione with the N-acetyl-tyrosyl-amine radical is (5 +/- 2) x 10 (8) M (-1) s (-1). In contrast, cysteine and glutathione react more slowly than their selenium analogues with the tyrosyl radical: the reactions of N-acetyl-tyrosyl-amine radicals with cysteine and glutathione are 3 and 5 orders of magnitude slower, respectively, than those with selenocysteine and selenoglutathione, while those of tyrosyl radicals in insulin are 3 and 2 orders of magnitude slower, respectively.


[Acute intracompartmental pressure syndrome in the foot of children and the young].
Acute intracompartmental pressure syndrome is a surgical emergency situation. The syndrome is rare and is most commonly associated with a high-energy trauma. It may occur also without trauma, for instance in muscular overloading. The syndrome should be suspected, when a child suffers from acute foot pain. The treatment is immediate compartment release surgery. A delay can be critical, because complications may remain persistent.


Autoimmune endocrine diseases.
The endocrine system is interested by several autoimmune diseases, characterized by different impact and severity, according to the organs involved. Autoimmune thyroid disorders (i.e. Hashimoto's thyroiditis and Graves' disease) and type 1 diabetes mellitus are the most common autoimmune endocrine disorders, while hypophysitis, adrenalitis (90% of cases of primary hypocortisolism or Addison's disease), POF and hypoparathyroidism represent quite rare conditions. Autoimmune endocrine diseases can also coexist in the same individuals and cluster in families. Some of these associations are nosologically codified in the so-called autoimmune polyglandular syndromes, but autoimmune endocrinopathies can also be accompanied by other non-endocrine autoimmune disorders (i.e. connective tissue, skin or gastrointestinal diseases). Pathophysiology generally results from a complex interplay among genetic predisposition and environmental/endogenous factors. In the diagnostic process, measurement of organ-specific autoantibodies, both with a causative role or as an epiphenomenon, is often fundamental and integrates the assessment of hormone axes and the targeted imaging studies.


Increase in left ventricular ejection rate during recovery from exercise in patients with myocardial infarction.
Changes in left ventricular (LV) ejection rate were evaluated during supine bicycle exercise and recovery in 12 patients with anterior myocardial infarction. Pulmonary artery wedge pressure (34 +/- 9 to 14 +/- 5 mm Hg) and plasma norepinephrine level decreased at 2 min recovery from peak exercise, whereas plasma lactate tended to increase. As a result, LV ejection rate reached the highest value at 2 min of recovery. Thus, both cardiac (optimal filling pressure) and peripheral factors (reduced vascular resistance) caused the increase in LV ejection rate at early recovery.


Coping patterns associated with long-term outcome from traumatic brain injury among female survivors.
In this study, we investigated the relationship between coping strategy and long-term outcome from traumatic brain injury (TBI) in a sample of 72 female TBI patients an average of five years post-injury. Using cluster analytic techniques based on two subscale sets from the Ways of Coping Questionnaire-Revised (WOC-R), we derived clinically relevant cluster groups based on coping strategy and validated the groups on demographic, injury-related, and quality of life measures. Results suggested that coping strategies characterized by low overall coping and positive reappraisal were associated with relatively good outcome, while those characterized by high overall coping and a combination of self-blame and escape avoidance were associated with relatively poorer outcome. These results are similar to those obtained with male samples, but societally linked gender stereotypes may contribute to unique coping and restriction of coping strategy for female TBI patients.


Study on cinnamon essential oil release performance based on pH-triggered dynamic mechanism of active packaging for meat preservation.
The regular release kinetics of active ingredients is inconsistent with the demand of meat preservation. Herein, the pH-triggered dynamic mechanism of packaging film was developed based on L100 polymer incorporated with Cinnamon essential oil (CEO) by coaxial electrospinning. The acquired results revealed that UV-vis and fluorescence spectra confirmed the pH release behavior. The fabricated film was quickly dissolved and transformed from solid to liquid phase, resulting in a faster release rate of CEO from 68.9 % to 98.2 % with the pH increasing. The morphological structure verified the core-shell structure formation with a specific surface area value of 7.22 m2/g. The live/dead results of bacteria indicated good antibacterial efficacy against E. coli and S. aureus. The pH-sensitive film successfully extends the shelf-life of griskin by 3 days. In conclusion, this work will aid in optimizing durability of active ingredients in packaging.