Systemic inflammation is associated with differential gene expression and airway neutrophilia in asthma.
Systemic inflammation is reported to be associated with neutrophilic airway inflammation in asthma, but mechanisms underlying this finding are not well understood. This study aimed to examine the molecular mechanisms of the airway neutrophilia that are associated with systemic inflammation in asthma. Fifty stable nonsmoking adults with asthma had plasma high sensitivity C-reactive protein (hsCRP) and interleukin 6 (IL-6) assayed. Subjects with an elevation of both hsCRP and IL-6 were grouped as asthmatics with systemic inflammation, and those with both hsCRP and IL-6 within the normal ranges were grouped as asthmatics without systemic inflammation. Clinical characteristics and sputum inflammatory cell counts were compared between the two groups. Gene expression profiles from sputum were analyzed and altered expression of four genes (CCL8, IL8RA, SELL, and PI3) was confirmed using quantitative PCR. Asthmatics with systemic inflammation (n=18, 36%) had a higher BMI, greater history of cigarette smoking, lower FVC% predicted, and increased sputum neutrophils compared to those without systemic inflammation (n=16, 32%). Microarray analysis identified 449 genes that were significantly altered in sputum between the two groups. Altered genes were involved in IL-1, TNF-α/nuclear factor-κB, and Kit receptor pathways, and were related to innate immune response, defense and inflammatory response, in particular neutrophilic inflammation. Systemic inflammation was associated with airway neutrophilia in asthma, and was related to a group of differentially expressed genes in the lung involving multiple cytokine pathways. Our findings suggest that targeting systemic inflammation might provide a novel therapeutic strategy for neutrophilic asthma.


Bats host the most virulent-but not the most dangerous-zoonotic viruses.
SignificanceThe clear need to mitigate zoonotic risk has fueled increased viral discovery in specific reservoir host taxa. We show that a combination of viral and reservoir traits can predict zoonotic virus virulence and transmissibility in humans, supporting the hypothesis that bats harbor exceptionally virulent zoonoses. However, pandemic prevention requires thinking beyond zoonotic capacity, virulence, and transmissibility to consider collective "burden" on human health. For this, viral discovery targeting specific reservoirs may be inefficient as death burden correlates with viral, not reservoir, traits, and depends on context-specific epidemiological dynamics across and beyond the human-animal interface. These findings suggest that longitudinal studies of viral dynamics in reservoir and spillover host populations may offer the most effective strategy for mitigating zoonotic risk.


Surgery in the age of biological treatment.
Surgery for IBD is in constant evolution; it does not appear that the introduction of biologicals has had a major effect on the chance of a patient being operated on or not. Pouch surgery had its heydays in the 80s and 90s and has since then become less frequent, but the number of patients undergoing surgery still seem about the same from one year to the other. Likewise, there is no substantial evidence that surgery for Crohn's disease is diminishing. There have been fears that patients on biological treatment have an increased risk of postoperative complications. The issue is not completely settled but it is likely that patients on biological treatment who come to surgery are those who do not benefit from biologicals. Thus, they are compromised in that they have an ongoing inflammation, are in bad nutritional state, and might have several other known risk factors for a complicated postoperative course. These factors and perhaps not the biologicals per se is what surgeons should consider. During the recent years, we have seen several new developments in IBD surgery; the ileorectal anastomosis is being used for ulcerative colitis and laparoscopic surgery usually resulting in a shorter hospital stay, less pain, and better cosmetics. We have also seen the introduction of robotic surgery, single incision minimal invasive surgery, transanal minimal invasive surgery, and other approaches to minimize surgical trauma. Time will show which of these innovations patients will benefit from.


Comparison of gamma and x-ray irradiation for myeloablation and establishment of normal and autoimmune syngeneic bone marrow chimeras.
Murine bone marrow (BM) chimeras are a versatile and valuable research tool in stem cell and immunology research. Engraftment of donor BM requires myeloablative conditioning of recipients. The most common method used for mice is ionizing radiation, and Cesium-137 gamma irradiators have been preferred. However, radioactive sources are being out-phased worldwide due to safety concerns, and are most commonly replaced by X-ray sources, creating a need to compare these sources regarding efficiency and potential side effects. Prior research has proven both methods capable of efficiently ablating BM cells and splenocytes in mice, but with moderate differences in resultant donor chimerism across tissues. Here, we compared Cesium-137 to 350 keV X-ray irradiation with respect to immune reconstitution, assaying complete, syngeneic BM chimeras and a mixed chimera model of autoimmune disease. Based on dose titration, we find that both gamma and X-ray irradiation can facilitate a near-complete donor chimerism. Mice subjected to 13 Gy Cesium-137 irradiation and reconstituted with syngeneic donor marrow were viable and displayed high donor chimerism, whereas X-ray irradiated mice all succumbed at 13 Gy. However, a similar degree of chimerism as that obtained following 13 Gy gamma irradiation could be achieved by 11 Gy X-ray irradiation, about 85% relative to the gamma dose. In the mixed chimera model of autoimmune disease, we found that a similar autoimmune phenotype could be achieved irrespective of irradiation source used. It is thus possible to compare data generated, regardless of the irradiation source, but every setup and application likely needs individual optimization.


Genetic association between coffee/caffeine consumption and the risk of obstructive sleep apnea in the European population: a two-sample Mendelian randomization study.
The association between coffee/caffeine consumption and obstructive sleep apnea (OSA) risk remains unclear. To determine the relationship between coffee/caffeine consumption and the risk of OSA, using the Mendelian randomization (MR) method in the European population. Two sets of coffee consumption-associated genetic variants were, respectively, extracted from the recent genome-wide meta-analysis (GWMA) and genome-wide association study (GWAS) of coffee consumption. Taking other caffeine sources into account, genetic variants associated with caffeine consumption from tea and plasma caffeine (reflecting total caffeine intake) were also obtained. The inverse variance weighted (IVW) technique was utilized as the primary analysis, supplemented by the MR-Egger, weighted-median, and MR-Pleiotropy RESidual Sum and Outlier (PRESSO) techniques. Leave-one-out (LOO) analysis was performed to assess whether the overall casual estimates were driven by a single SNP. Additional sensitivity analyses were performed using similar methods, while the genetic variants associated with confounders, e.g., body mass index and hypertension, were excluded. The IVW method demonstrated that coffee consumption GWMA (OR: 1.065, 95% CI 0.927-1.224, p = 0.376), coffee consumption GWAS (OR: 1.665, 95% CI 0.932-2.977, p = 0.086), caffeine from tea (OR: 1.198, 95% CI 0.936-1.534, p = 0.151), and blood caffeine levels (OR: 1.054, 95% CI 0.902-1.231, p = 0.508) were unlikely to be associated with the risk of OSA. The other three methods presented similar results, where no significant associations were found. No single genetic variant was driving the overall estimates by the LOO analysis. These findings were also supported by the sensitivity analyses with no confounding genetic variants. Our study found no association between coffee/caffeine consumption and the risk of OSA.


Triggering the sintering of silver nanoparticles at room temperature.
A new approach to achieve coalescence and sintering of metallic nanoparticles at room temperature is presented. It was discovered that silver nanoparticles behave as soft particles when they come into contact with oppositely charged polyelectrolytes and undergo a spontaneous coalescence process, even without heating. Utilizing this finding in printing conductive patterns, which are composed of silver nanoparticles, enables achieving high conductivities even at room temperature. Due to the sintering of nanoparticles at room temperature, the formation of conductive patterns on plastic substrates and even on paper is made possible. The resulting high conductivity, 20% of that for bulk silver, enabled fabrication of various devices as demonstrated by inkjet printing of a plastic electroluminescent device.


Diversification of the rice Waxy gene by insertion of mobile DNA elements into introns.
The waxy (wx) gene of Oryza glaberrima was cloned, and its nucleotide sequence was determined. A waxy mutant of O. glaberrima showing a glutinous phenotype was found to contain a substitution mutation generating a termination codon in the coding region of the wx gene. The Wx sequence of O. glaberrima was different from that of Oryza sativa by substitutions and insertions/deletions, among which only a few substitutions occurred in several exons not to severely alter the amino acid sequence of the Wx protein. The most striking difference observed in introns was a 139-bp deletion (or insertion) in intron 10 of O. glaberrima (or O. sativa). In O. sativa, 125 bp of the 139-bp sequence was flanked by direct repeats of a 14-bp sequence. A sequence homologous to the 125-bp sequence was found in the region preceding exon 2; this sequence was also flanked by direct repeats of another 14-bp sequence. This result and the observation that the 125-bp sequence was interspersed in rice genomes indicate that they are SINEs (short interspersed elements) in the plant system. We also identified a DNA sequence with long terminal inverted repeats in intron 13 of both O. glaberrima and O. sativa. This sequence was present in multiple copies in rice genomes, suggesting that it is a transposable element. These results obtained suggest that mobile DNA elements have diversified the rice Waxy gene by inserting into introns, each of which may originally have a length of about 100 bp.


Chiral Gd-DOTA as a Versatile Platform for Hepatobiliary and Tumor Targeting MRI Contrast Agents.
The leakage of gadolinium ions (Gd3+) from commercial Gd3+-based contrast agents (GBCAs) in patients is currently the major safety concern in clinical magnetic resonance imaging (MRI) scans, and the lack of task-specific GBCAs limits its usage in the early detection of disease and imaging of specific biological regions. Herein, ultrastable GBCAs were constructed via decorating chiral Gd-DOTA with a phenylic analogue to one of the pendent arms, and the stability constant was determined as high as 27.08, accompanied by negligible decomplexation in 1 M of HCl over 2 years. A hepatic-specific chiral Gd-DOTA was screened out as a potential alternative to commercial Gd-EOB-DTPA, while combination with functional molecules favored chiral Gd-DOTA as tumor targeting probes. Therefore, the novel chiral Gd-DOTA is believed to be an ideal platform for designing the next generation of GBCAs for various clinical purposes due to its outstanding inert nature.


Physico-chemical characteristics of Anopheles culicifacies and Anopheles varuna breeding water in a dry zone stream in Sri Lanka.
Selected physico-chemical characteristics of flowing and pooled water in a stream that generated two malaria vectors, Anopheles culicifacies s.l. Giles and Anopheles varuna Iyengar, were investigated during August-September 1997 and July 1998 at the Upper Yan Oya watershed in north-central Sri Lanka. The physico-chemical parameters measured were: temperature, dissolved oxygen, pH, conductivity, total dissolved solids, alkalinity, ammonia nitrogen, nitrate nitrogen, calcium, magnesium, carbondioxide, ferrous iron, phosphate, colour and turbidity. In total, 75.5% of 151 samples analysed were mosquito-positive. Logistic regression was used for statistical analysis. Among physico-chemical parameters, An. culicifacies (the major malaria vector in the country) was positively related only to temperature, and An. varuna (a secondary malaria vector) to calcium. Among habitat characteristics, An. culicifacies was associated with light and vegetation, and negatively associated with the presence of potential predators. An. varuna was positively associated with other aquatic fauna. Surprisingly this detailed study did not find an association between An. culicifacies and dissolved oxygen as previously found in the few studies that have looked at physico-chemical characteristics of malaria vector breeding habitats in south Asia. This study, along with existing information from other studies indicate that most of the physico-chemical parameters measured under natural conditions within the same habitat type is insufficient to explain the distribution of vectors within such habitats. However, it seems likely that both An. culicifacies and An. varuna follow a strategy whereby ovipositing females scatter their eggs over most of or all of a highly temporary and only transiently available stream bed pool habitat, in order to optimise breeding success.


Traditional prosthetic workflow for implant rehabilitations with a reduced number of fixtures: proposal of a protocol.
The aim of this study was to describe a standardized protocol for the creation of a definitive prosthetic rehabilitation supported by a reduced number of implants, achievable with a limited number of an optimized appointments. The proposed protocol provides only for 4 appointments to finalize the set work. During the first appointment, definitive impressions are taken in order to obtain the master models and plaster bars. The second appointment is the most important: the aesthetic and functional evaluations of the provisional prostheses are carried out and the plaster bars tested. During the third appointment the teeth test is performed, with the corresponding phonetic and functional test. In the fourth appointment the definitive prostheses are delivered and screwed. The fundamental aspect of prosthetic finalization is the simplification and standardization of protocols to obtain better control of all different steps and to reduce the number of appointments with the patient. The realization of a correct definitive prosthesis is the key to long-term success in implant rehabilitation and can improve the patient's quality of life in various aspects. By optimising the time and standardising the procedures, it is possible to make definitive prostheses for rehabilitations with a reduced number of implants of excellent quality in only 4 appointments.


Nigella sativa and Cancer: A Review Focusing on Breast Cancer, Inhibition of Metastasis and Enhancement of Natural Killer Cell Cytotoxicity.
In the last decade, there have been accumulating data that the use of medicinal plants could bring additional benefits to the supportive treatment of various diseases. Nigella sativa (N. sativa, family Ranunculaceae) is one of these plants that has attracted considerable interest. The extracts and seeds of N. sativa and its active component thymoquinone have been studied extensively and the results suggest that N. sativa might carry some therapeutic potential for many diseases, including cancer. The selection criteria for references were applied through Pubmed with "N. sativa and cancer", "N. sativa and breast cancer", "N. sativa and metastasis", "N. sativa and cytotoxicity of natural killer cells". The pathway analysis was performed using the PANTHER tool by using five randomly selected N. sativa affected genes (Cyclin D1, P53, p21 protein (Cdc42/Rac) activated kinase 1 (PAK1), B-cell lymphoma 2 (Bcl-2) and vascular endothelial growth factor (VEGF)) in order to elucidate further potentially affected signaling pathways. The aim of this review was to summarize studies regarding the effects of N. sativa in cancer generally, with a focus on breast cancer, its anti-metastatic effects, and how N. sativa modulates the cytotoxicity of Natural Killer cells that play a crucial role in tumor surveillance. In summary, the data suggest that N. sativa might be used for its anti-cancer and antimetastatic properties and as an immune system activator against cancer.


High autumn temperature delays spring bud burst in boreal trees, counterbalancing the effect of climatic warming.
The effect of temperature during short-day (SD) dormancy induction was examined in three boreal tree species in a controlled environment. Saplings of Betula pendula Roth, B. pubescens Ehrh. and Alnus glutinosa (L.) Moench. were exposed to 5 weeks of 10-h SD induction at 9, 15 and 21 degrees C followed by chilling at 5 degrees C for 40, 70, 100 and 130 days and subsequent forcing at 15 degrees C in a 24-h photoperiod for 60 days. In all species and with all chilling periods, high temperature during SD dormancy induction significantly delayed bud burst during subsequent flushing at 15 degrees C. In A. glutinosa, high temperature during SD dormancy induction also significantly increased the chilling requirement for dormancy release. Field experiments at 60 degrees N with a range of latitudinal birch populations revealed a highly significant correlation between autumn temperature and days to bud burst in the subsequent spring. September temperature alone explained 20% of the variation between years in time of bud burst. In birch populations from 69 and 71 degrees N, which ceased growing and shed their leaves in August when the mean temperature was 15 degrees C, bud burst occurred later than expected compared with lower latitude populations (56 degrees N) in which dormancy induction took place more than 2 months later at a mean temperature of about 6 degrees C. It is concluded that this autumn temperature response may be important for counterbalancing the potentially adverse effects of higher winter temperatures on dormancy stability of boreal trees during climate warming.


Otitis media: To treat or not to treat?
Acute otitis media affects at least 80% of children younger than two years of age and is responsible for a third of physician visits of children younger than five years of age. Diagnosis must be based on more than an injected tympanic membrane; systemic signs and symptoms such as fever, irritability and reduced appetite are important, as is reduced mobility of the ear drum assessed with pneumatic otoscopy or impedance tympanometry. Once otitis media has been accurately diagnosed, treatment with antibiotics appears to improve outcomes and to reduce complications, such as mastoiditis, although results from different studies conflict.


Immunogenicity and reactogenicity of primary immunization with a novel combined Haemophilus influenzae Type b and Neisseria meningitidis Serogroup C-tetanus toxoid conjugate vaccine coadministered with a Diphtheria-tetanus-acellular Pertussis-hepatitis B-inactivated poliovirus vaccine at 2, 4 and 6 months.
This phase II study evaluated the immunogenicity and reactogenicity of primary vaccination with a novel Hib-MenC conjugate vaccine (GlaxoSmithKline [GSK] Biologicals) coadministered with DTPa-HBV-IPV (GSK Biologicals) at 2, 4 and 6 months. Healthy infants were randomized to receive Hib-MenC coadministered with DTPa-HBV-IPV (N = 117) or MenC-CRM (Wyeth) coadministered with DTPa-HBV-IPV/Hib (GSK Biologicals; N = 120) at 2, 4 and 6 months. Antibody concentrations were measured before vaccination and after doses 2 and 3. Solicited local and general symptoms, unsolicited symptoms and serious adverse events (SAEs) were recorded. All subjects in the Hib-MenC group had seroprotective titers of anti-PRP antibodies (>or=0.15 microg/mL) and SBA-MenC titers (>or=1:8) 1 month after the third dose. These responses were noninferior to those seen in the control group, in which a 99.1% seroprotection rate was observed for both Hib and MenC. At that time, anti-PRP and SBA-MenC GMTs were significantly higher in the Hib-MenC group (12.8 microg/mL and 2467.1 microg/mL, respectively) than in the control group (3.8 microg/mL and 1833.7 microg/mL). High seroprotection rates were already observed after the second dose of Hib-MenC; 96.4% and 100% of subjects were seroprotected to Hib and MenC, respectively. Immune responses to coadministered antigens were unimpaired; seroprotection/vaccine response rates >or=96.5% were recorded postdose 3 in the Hib-MenC group. No differences in reactogenicity were seen between the 2 study groups. Coadministration of a Hib-MenC conjugate vaccine with DTPa-HBV-IPV is well tolerated and immunogenic, and does not impair the immune response to any of the coadministered antigens.


Regulation of B cell responses to the variant surface glycoprotein (VSG) molecule in trypanosomiasis. I. Epitope specificity and idiotypic profile of monoclonal antibodies to the VSG of Trypanosoma brucei rhodesiense.
Regulatory mechanisms governing B cell responses to the trypanosome variant surface glycoprotein (VSG) molecule currently are being studied. As a fundamental basis for examining such regulation, the epitope specificities and idiotypic profiles of murine mAb produced to the VSG of Trypanosoma brucei rhodesiense clone LouTat 1.5 were determined. Variant specific mAb were used to probe VSG proteolytic peptides in Western blot analysis, to serve as competitive inhibitors in RIA analyses with purified VSG molecules, and to examine membrane-binding patterns of labeled trypanosome cells in order to evaluate epitope specificities. By using these approaches, a conformational epitope expressed only on the VSG 1.5 surface coat of viable trypanosomes was detected, and two nonconformationally determined epitope clusters were recognized within the subsurface V region of the VSG 1.5 molecule. The subsurface epitope clusters may be repeated on the VSG molecule because each was present on more than one proteolytic VSG peptide fragment. Idiotypic profiles of selected VSG-specific mAb subsequently were determined with xenogeneic antiidiotypic typing sera. Results from competitive inhibition RIA analyses using these reagents demonstrated that varying levels of idiotypic cross-reactivity exist among the subsurface VSG epitope-specific mAb; this cross-reactivity extended to idiotope(s) expressed by a mAb recognizing a surface conformational epitope of the VSG 1.5 molecule. Analysis of complementary idiotypic/antiidiotypic antibody pairs revealed that these specific interactions were inhibited by purified VSG 1.5 but not by purified VSG 1.9, which was derived from a heterologous variant antigenic type. The model mAb described here, and reagents recognizing their idiotypic markers, comprise a foundation for analysis of idiotypic regulation of VSG-specific B cell responses during infection.


Determining the optimal number of individual samples to pool for quantification of average herd levels of antimicrobial resistance genes in Danish pig herds using high-throughput qPCR.
The primary objective of this study was to determine the minimum number of individual fecal samples to pool together in order to obtain a representative sample for herd level quantification of antimicrobial resistance (AMR) genes in a Danish pig herd, using a novel high-throughput qPCR assay. The secondary objective was to assess the agreement between different methods of sample pooling. Quantification of AMR was achieved using a high-throughput qPCR method to quantify the levels of seven AMR genes (ermB, ermF, sulI, sulII, tet(M), tet(O) and tet(W)). A large variation in the levels of AMR genes was found between individual samples. As the number of samples in a pool increased, a decrease in sample variation was observed. It was concluded that the optimal pooling size is five samples, as an almost steady state in the variation was observed when pooling this number of samples. Good agreement between different pooling methods was found and the least time-consuming method of pooling, by transferring feces from each individual sample to a tube using a 10μl inoculation loop and adding 3.5ml of PBS, approximating a 10% solution, can therefore be used in future studies.


Evolution of functional cyclohexadiene-based synthetic reagents: the importance of becoming aromatic.
Suites of new precursors designed around a cyclohexadiene core and intended to mediate "clean" radical chain syntheses have been prepared and tested. 1-Functionalized cyclohexa-2,5-dienes were found to readily donate H-atoms, and the resulting cyclohexadienyl radicals rapidly extruded their functional group as a free radical, because this beta-scission restored aromaticity to the ring. This concept was employed to generate designer radicals from esters of the corresponding alcohols with 1-methyl- or 1-phenylcyclohexa-2,5-diene-1-carboxylic acids. In a similar way, pre-adapted carbamoyl radicals were obtained from cyclohexadienyl-amides and proved advantageous for syntheses of alpha- and beta-lactams. Oxime ether substituted carbamoyl radicals cyclized successfully in convenient syntheses of dihydroindolin-2-ones with N-functionality at the 3-position. Similarly, silicon-centered radicals were obtained from 1-silylated cyclohexadienes, and these reagents proved to be very efficient, environmentally benign organotin hydride substitutes. Radical reactions including reductions, cyclizations, intermolecular additions, and hydrosilylations were carried out in high yields with this reagent. Other heteroatom-centered radicals, especially N-centered radicals, were obtained from appropriate cyclohexadienes enabling chain hydroaminations to be conducted. Several of the cyclohexadiene precursors proved to be useful for electron paramagnetic resonance (EPR) spectroscopic purposes, and this enabled rate constants for fragmentations of the cyclohexadienyl radicals to be obtained. Kinetic data for H-atom abstraction from cyclohexadienes, the second propagation step of the chain processes, was derived from customized radical clocks and from EPR measurements. In this way, conceptual tools were developed for improving future synthetic methodology based around these reagents.


Calculating potentials of mean force from steered molecular dynamics simulations.
Steered molecular dynamics (SMD) permits efficient investigations of molecular processes by focusing on selected degrees of freedom. We explain how one can, in the framework of SMD, employ Jarzynski's equality (also known as the nonequilibrium work relation) to calculate potentials of mean force (PMF). We outline the theory that serves this purpose and connects nonequilibrium processes (such as SMD simulations) with equilibrium properties (such as the PMF). We review the derivation of Jarzynski's equality, generalize it to isobaric--isothermal processes, and discuss its implications in relation to the second law of thermodynamics and computer simulations. In the relevant regime of steering by means of stiff springs, we demonstrate that the work on the system is Gaussian-distributed regardless of the speed of the process simulated. In this case, the cumulant expansion of Jarzynski's equality can be safely terminated at second order. We illustrate the PMF calculation method for an exemplary simulation and demonstrate the Gaussian nature of the resulting work distribution.


Association of non-invasive hemodynamics with arterial stiffness in rheumatoid arthritis.
Arterial stiffness has emerged as a surrogate marker of cardiovascular disease. We investigated the role of myocardial performance and hemodynamic parameters in arterial stiffness in patients with rheumatoid arthritis (RA), which is accompanied by excess cardiovascular risk. Arterial stiffness was evaluated with pulse wave velocity (PWV) in RA patients and controls. Cardiac and hemodynamic characterization was based on impedance cardiography. Cardiovascular risk factors, inflammatory markers and disease-related parameters were assessed. PWV (8.2 ± 2.1 vs 7.4 ± 1.4 m/s, p = .016) was higher among RA patients (n = 104) compared to controls (n = 52). In the RA group, PWV correlated with markers of cardiac contractibility (acceleration and velocity index), myocardial blood flow (cardiac output and stroke volume), preload (thoracic fluid content) and afterload (systemic vascular resistance) (p < .05 for all). PWV tended to increase with decreasing oxygen delivery to the myocardium (r = 0.055), as well as with shortening of the ejection duration of the left ventricle (p = .058). However, these associations no longer remained significant after adjustment for classical cardiovascular risk factors, inflammation and corticosteroid use, which were independently associated with PWV. Among patients with RA, arterial stiffness appears as the composite of cardiovascular risk factors and inflammation, while corticosteroid use emerges as an additional adverse factor.


Ultrastructural changes in limb distal nerves of rats with alcoholism and/or malnutrition before and after dietary correction.
To study peripheral nerves changes in chronic alcoholism and in malnutrition, we examined ultrastructurally the distal nerve branches of the digits of rats treated with four different dietary schemes, as follows: controls (n = 22), fed standard rodent diet plus water ad libitum; alcoholism (n = 12), fed the standard diet and 2-12% ethanol in drinking water; malnutrition (n = 21), fed with corn tortillas instead of standard diet; and alcoholism and malnutrition combined (n = 22). After 10 months under these conditions, a proportion of animals from each group were sacrificed. The remaining rats of the malnutrition and alcoholism alone groups were deferred a standard diet. The combined alcohol + malnutrition group was subdivided into standard diet, malnutrition and ethanol. After a further 4 months under these new conditions, the animals were sacrificed. Ultrastructural examination of limb distal nerve branches showed that glycogen-like particles were more common in malnourished animals, whereas remyelinating axons were more numerous in ethanol-treated rats. Bands of regeneration were present in both groups, but were more common in animals treated with ethanol. These features decreased significantly when the respective nutritional factor was reversed. The results confirm that ethanol plays a definitive role in the development of alcoholic neuropathy and that malnutrition accentuates, the histopathological abnormalities.


Dialysate composition and hemodialysis hypertension.
Dialysis prescriptions have evolved to take advantage of new technology and serve a burgeoning patient population. High-sodium bicarbonate-based dialysate was first formulated in 1982 to enable short, safe, comfortable, high-efficiency hemodialysis (HD). Near-universal adaptation of these high-sodium formulas has virtually eliminated profound dialysis disequilibrium and greatly reduced dialysis discomfort, but has created a syndrome of dialysis salt loading with accentuated postdialysis thirst, interdialytic weight gain, and hypertension. Available technology will soon permit individuals to receive isonatremic dialysis with dialysate customized to the patient's serum sodium activity. Then, rather than choosing between comfortable, safe, high-efficiency dialysis with salt loading; cramps, asthenia, and symptomatic hypotension using low-sodium, high-efficiency rapid HD to control blood pressure (BP) and weight gain; or comfortable, slow, low-efficiency HD with BP control, physicians may be able to minimize symptoms and avoid dialysis salt loading while providing maximum time for rehabilitative activities. The current use of a single sodium activity for all patients ignores the inter- and intraindividual variability in serum sodium activity in our patients. This results in undesired consequences for 20-40% of patients. The application of even more severe salt loading through high-salt sodium modeling only accentuates the long-term problems of excessive thirst, weight gain, and hypertension.


Impact of PUFA on early immune and fetal development.
It has recently been reported that the increased prevalence in childhood allergy may be linked to deviations in fetal immune development. One reason may be impaired nutrient supply. Hence, a well-differentiated placenta together with an optimal fetal nutrition via the mother are important prerequisites for the establishment of a functional immune system with normal immune responses. Fatty acids and their derivatives can influence both the early immune development and immune maturation by regulating numerous metabolic processes and the gene expression of important proteins such as enzymes and cytokines. The present review summarises the impact of nutritional fatty acids on the development of the immune system as well as the fetal development. It describes the mechanisms of action of PUFA, trans fatty acids and conjugated linoleic acids in programming the fetus with regard to its risk of acquiring atopic diseases in childhood.


6q deletions in acute lymphoblastic leukemia and non-Hodgkin's lymphomas.
Deletions on the long arm of chromosome 6 are frequently found in acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphomas (NHL). We have used polymerase chain reaction analysis to study loss of heterozygosity of 16 microsatellite markers on chromosome 6 in 74 ALL and 54 NHL patients. Our results show that deletions of 6q in ALL are more frequent than what has been reported in previous studies, occurring in at least 32% of the patients. The corresponding figure for NHL patients is 7%. Our results define a region of minimal deletion in ALL of less than 500 kb between markers D6S1709 and D6S434. The common region of deletion in NHL is located telomeric of this region. Thus, two different tumor suppressor genes on chromosome 6q seem to be relevant for the development of lymphoid malignancies.


Characteristics of Corneal Higher-Order Aberrations in Congenital Ectopia Lentis Patients.
The purpose of this study was to investigate the characteristics of corneal higher-order aberrations (HOAs) in patients with congenital ectopia lentis (CEL). Clinical characteristics and HOAs of 60 patients with CEL and 75 healthy controls at Zhongshan Ophthalmic Center in China were retrospectively analyzed. The Q value and the corneal HOAs in the CEL group and the controls were measured by using Pentacam and compared value between the CEL and control groups. The correlation between HOAs and age was investigated using the Pearson correlation analysis. The Q value of anterior corneal surface in the CEL group was larger than that in the controls (-0.41 ± 0.17 vs. -0.32 ± 0.13, P = 0.001); the total corneal horizontal coma in the CEL group were larger than that in the controls (0.24 ± 0.18 vs. -0.05 ± 0.14, P < 0.001); both the primary spherical aberrations of the anterior and total corneal surface were lower in the CEL group than that in the controls (for anterior corneal surface: 0.15 ± 0.08 vs. 0.27 ± 0.08 µm, P < 0.001; for total corneal surface: 0.10 ± 0.09 vs. 0.23 ± 0.09 µm, P < 0.001), the anterior and total corneal horizontal coma were negatively associated with age, whereas the anterior and total corneal spherical aberrations were positively associated with age in patients with CEL. Patients with CEL had higher corneal horizontal coma and lower corneal vertical coma primary spherical aberrations than healthy controls. These findings are informative for the clinical managements in patients with CEL.


Identification of Mallory bodies with rhodamine B fluorescence and other stains for keratin.
Rhodamine B staining in conjunction with fluorescence microscopy is shown to demonstrate Mallory bodies. Mallory body morphology, localization, and distribution in hepatocytes from griseofulvin-fed mice, human hepatoma, and human alcoholics were similar to those observed in the same tissues after conventional staining methods for Mallory bodies. The presence of these inclusions was further confirmed by specific cytochemical localization with indirect immunoperoxidase labeling, horseradish peroxidase labeling, and electron microscopy. Other tinctorial or histochemical procedures previously used for keratin or prekeratin (modified Mallory stain, Kreyberg method, Pauly method for histidine) also stained Mallory bodies for study with white light microscopy but with decreasing sensitivity respectively. Mallory bodies from mouse and human liver both appear to contain a keratin-like moiety. This entity may be simply, rapidly, and permanently stained with rhodamine B, and selectively and reproducibly demonstrated with fluorescence microscopy.


Catalytic Performance of Microwave Functionalized NH2-MIL-53 for Cyclic Carbonate Synthesis from CO2 and Epoxides.
The efficacy of microwave irradiation in the quaternization of amino-functionalized MIL-53 metal-organic framework (MOF) as well as the catalytic activity of the resultant MOF in the cycloaddition of carbon dioxide with epoxides under solvent-free conditions has been studied. A series of NH2-MIL-53 were synthesized and quaternized by reacting alkyl halide of various alkyl chains and anions under microwave irradiation. The post-functionalized F-MIL-53-AXs were characterized through solid-state XRD, FT-IR, XPS, and TGA. F-MIL-53-Mel prepared by microwave method showed higher AGC yield than that by the conventional heating method. F-MIL-53-AXs with iodide anion exhibited the best catalytic activity irrespective of the alkyl chain length, in agreement with the generally accepting order of nucleophilicity, Cl<Br<I. A plausible mechanism in which Lewis acidic metal center and quaternary ammonium functional group operate synergistically is proposed. The F-MIL-53-AX catalysts were found to exhibit high thermal stability and were reusable over than three times, without any significant lowering of activity.


Using a pipeline to improve de-identification performance.
Effective de-identification methods are needed to support reuse of electronic health record data for research and other purposes. We investigated using two different text-processing systems in tandem as a strategy for de-identification of clinical notes. We ran 100 outpatient notes through deid.pl, from MIT's PhysioToolkit, followed by MedLEE, and we manually compared the output with original notes to determine the amount of protected health information (PHI) retained. Pipelining resulted in an overall error rate of 2%, with 2 personal names retained in output: one initial and a commonly used English term used in medicine. All retained PHI was transformed into standardized medical concepts, making re-identification less likely. Pipelining using deid.pl improved performance of MedLEE in excluding PHI from output and may be a useful strategy for de-identifying clinical data while providing computer-readable output.


Percutaneous Radiofrequency Ablation for Liver Tumors: Technical Tips.
Percutaneous radiofrequency ablation (RFA) has been accepted as a minimally invasive therapeutic treatment for liver malignancies. Although RFA is usually applied for the treatment of small liver tumors (<3 cm), several technical developments have expanded the use of RFA. RFA is now used for the treatment of large liver tumors, and the number of complications associated with this treatment has decreased. These refinements may ultimately lead to better long-term prognosis. Here, we review recent refinements of liver RFA and provide technical tips.


Genetic Variants in HSD17B3, SMAD3, and IPO11 Impact Circulating Lipids in Response to Fenofibrate in Individuals With Type 2 Diabetes.
Individuals with type 2 diabetes (T2D) and dyslipidemia are at an increased risk of cardiovascular disease. Fibrates are a class of drugs prescribed to treat dyslipidemia, but variation in response has been observed. To evaluate common and rare genetic variants that impact lipid responses to fenofibrate in statin-treated patients with T2D, we examined lipid changes in response to fenofibrate therapy using a genomewide association study (GWAS). Associations were followed-up using gene expression studies in mice. Common variants in SMAD3 and IPO11 were marginally associated with lipid changes in black subjects (P < 5 × 10-6 ). Rare variant and gene expression changes were assessed using a false discovery rate approach. AKR7A3 and HSD17B13 were associated with lipid changes in white subjects (q < 0.2). Mice fed fenofibrate displayed reductions in Hsd17b13 gene expression (q < 0.1). Associations of variants in SMAD3, IPO11, and HSD17B13, with gene expression changes in mice indicate that transforming growth factor-beta (TGF-β) and NRF2 signaling pathways may influence fenofibrate effects on dyslipidemia in patients with T2D.


PFOS dominates PFAS composition in ambient fine particulate matter (PM2.5) collected across North Carolina nearly 20 years after the end of its US production.
Contamination of drinking water by per- and polyfluoroalkyl substances (PFASs) emitted from manufacturing plants, fire-fighting foams, and urban waste streams has received considerable attention due to concerns over toxicity and environmental persistence; however, PFASs in ambient air remain poorly understood, especially in the United States (US). We measured PFAS concentrations in ambient fine particulate matter (PM2.5) at 5 locations across North Carolina over a 1 year period in 2019. Thirty-four PFASs, including perfluoroalkyl carboxylic, perfluoroalkane sulfonic, perfluoroalkyl ether carboxylic and sulfonic acids were analyzed by UHPLC/ESI-MS/MS. Quarterly averaged concentrations ranged from <0.004-14.1 pg m-3. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) ranged from <0.18 to 14.1 pg m-3, comparable to previous PM2.5 measurements from Canada and Europe (<0.02-3.5 pg m-3). Concentrations above 1 pg m-3 were observed in July-September at Charlotte (14.1 pg m-3, PFOA), Wilmington (4.75 pg m-3, PFOS), and Research Triangle Park (1.37 pg m-3, PFOS). Notably, PM2.5 has a short atmospheric lifetime (<2 weeks), and thus, the presence of PFOS in these samples raises questions about their sources, since PFOS production was phased out in the US ∼20 years ago. This is the first US study to provide insights into ambient PFAS concentrations in PM2.5.


Increased frequency of CD27- (naive) B cells and their phenotypic alteration in HIV type 1-infected patients.
To investigate HIV-1-related B cell disorders, the quantity of peripheral CD27 negative (CD27-) B cells, their CD38, CD95, and bcl-2 intensities, and their apoptosis susceptibility were examined by flow cytometry analysis in 16 drug-naive patients, 27 HAART-treated patients, and 20 uninfected controls. CD27- B cells have been recognized as naive B cells. The mean percentage of CD27- B cells was significantly higher in drugnaive patients (88.1%) and in HAART-treated patients (83.9%) than in controls (68.6%) (p < 0.01). The intensities of CD38 and CD95 on CD27- B cells were significantly higher in drug-naive patients than in controls (p < 0.01). The intensity of CD95 on CD27- B cells in HAART-treated patients was lower than that of drug-naive patients, but significantly higher than that of controls (p < 0.01). The intensity of bcl-2 on CD27- B cells in drug-naive patients was lower than that of controls. In drug-naive patients, CD27-B cells with high CD38 expression represented low bcl-2 expression. The CD27- B cells of drug-naive patients showed an increased susceptibility to apoptosis, characterized by diminished cell size and a high frequency of annexin-V binding, compared with controls and HAART-treated patients. These findings suggested that HIV-1 infection affects peripheral CD27- (naive) B cells as well as CD27+ (memory) B cells and that CD27- B cells might be activated and rendered highly susceptible to apoptosis by HIV-1 infection. Some phenotypic alterations in CD27- B cells may continue after the reduction of HIV-1 loads by effective antiviral therapy.


Transport of chemical signals in systemic acquired resistance.
Systemic acquired resistance (SAR) is a form of broad-spectrum resistance induced in response to local infections that protects uninfected parts against subsequent secondary infections by related or unrelated pathogens. SAR signaling requires two parallel branches, one regulated by salicylic acid (SA), and the other by azelaic acid (AzA) and glycerol-3-phosphate (G3P). AzA and G3P function downstream of the free radicals nitric oxide (NO) and reactive oxygen species (ROS). During SAR, SA, AzA and G3P accumulate in the infected leaves, but only a small portion of these is transported to distal uninfected leaves. SA is preferentially transported via the apoplast, whereas phloem loading of AzA and G3P occurs via the symplast. The symplastic transport of AzA and G3P is regulated by gating of the plasmodesmata (PD). The PD localizing proteins, PDLP1 and PDLP5, regulate SAR by regulating PD gating as well as the subcellular partitioning of a SAR-associated protein.


Molecular motion and order in single-bilayer vesicles and multilamellar dispersions of egg lecithin and lecithin-cholesterol mixtures. A deuterium nuclear magnetic resonance study of specifically labeled lipids.
Deuterium (2H) nuclear magnetic resonance (NMR) quadrupole splittings and relaxation times have been measured for a variety of specifically deuterated lipids intercalated in lamellar-multibilayer dispersions and single-bilayer vesicles of egg lecithin and lecithin-cholesterol mixtures. The deduced order parameters and relaxation times vary with position of deuteration, acyl chain length, unsaturation, and temperature. The order parameters and spinlattice relaxation times T1 indicate rapid intramolecular motions of restricted amplitude in both the choline head group and hydrocarbon chains. The ordering profile for the acyl chains is similar to that predicted by statistical-mechanical theory. The order parameters yield estimates of the bilayer thickness and linear coefficient of expansion in close agreement with the x-ray determinations. A comparison of the deuterium and electron spin resonance spinprobe order parameters demonstrates the perturbation of the bilayer by the bulky nitroxide probe. The transverse relaxation time T2 for single-bilayer vesicles is quantitatively accounted for by a simple modification of classical relaxation theory which takes into account the modulation of the static quadrupole interaction by rapid local molecular motions and the modulation of the residual quadrupole interaction by the slower overall tumbling of the vesicle. It is unambiguously demonstrated that molecular motion and order in single-bilayer vesicles are very similar to those in lamellar multibilayers. Significant differences occur only for a few segments near the terminal methyl groups of the acyl chains, where the order parameters for vesicles are 10-30% smaller than those found for lamellae. The incorporation of cholesterol in lecithin bilayers is shown to increase the degree of orientational order in vesicles and lamellae, and to increase the hydrodynamic radius of vesicles. Thus, single-bilayer vesicles and multilamellar dispersions of phospholipids are equally useful models for biological membranes. They yield equivalent information about the internal organization and mobility of lipid bilayers, when the spectral manifestations of overall vesicle motion are correctly taken into account.


Hen egg white ovomacroglobulin promotes fibroblast migration via mediating cell adhesion and cytoskeleton.
Hen egg white ovomacroglobulin (OVM) possesses a variety of bioactivities and could potentially be used as a pharmaceutical agent. It has been reported that OVM is involved in wound healing and cancer pathological processes, and previous results suggest that OVM plays a potential role in cell proliferation and migration; however, this has not yet been proven. In the present study, the effects of OVM on fibroblast proliferation and migration were evaluated. Results of cell counting, cell viability, and cell cycle indicated that proliferation of fibroblasts was not altered by OVM treatment. However, scratch assays showed that OVM could promote the migration of 3 T6 mouse embryonic fibroblasts and human skin fibroblasts (HSF). Also, the adhesion of HSF to the collagen matrix was also enhanced by OVM treatment. RT-qPCR and western blot analysis showed that β1 -integrin, β-tubulin, and β-actin were up-regulated while E-cadherin was down-regulated in OVM-treated HSF cells. The effect of OVM was silenced after forming a complex with trypsin, suggesting that the protease inhibitory ability of OVM is important for its effect on cell migration. These results suggested that promotion of OVM on cell migration was achieved by enhancing cell adhesion to extracellular matrix, reducing intercellular aggregation, and strengthening cytoskeleton. The finding of the promotion effect of OVM on cell migration is important for understanding its role in wound healing and cancer pathological processes. © 2015 Society of Chemical Industry.


Molecular response to nitrogen starvation by Frankia alni ACN14a revealed by transcriptomics and functional analysis with a fosmid library in Escherichia coli.
The transcriptome of Frankia alni strain ACN14a was compared between in vitro ammonium-replete (N-replete) and ammonium-free dinitrogen-fixing (N-fixing) conditions using DNA arrays. A Welch-test (p < 0.05) revealed significant upregulation of 252 genes under N-fixing vs. N-replete (fold-change (FC) ≥ 2), as well as significant downregulation of 48 other genes (FC ≤ 0.5). Interestingly, there were 104 Frankia genes upregulated in vitro that were also significantly upregulated in symbiosis with Alnus glutinosa, while the other 148 genes were not, showing that the physiology of in vitro fixation is markedly different from that under symbiotic conditions. In particular,in vitro fixing cells were seen to upregulate genes identified as coding for a nitrite reductase, and amidases that were not upregulated in symbiosis. Confirmatory assays for nitrite reductase showed that Frankia indeed reduced nitrite and used it as a nitrogen source. An Escherichia coli fosmid clone carrying the nirB region was able to grow better in the presence of 5 mM nitrite than without it, confirming the function of the genome region. The physiological pattern that emerges shows that Frankia undergoes nitrogen starvation that induces a molecular response different from that seen in symbiosis.


The cellular and molecular carcinogenic effects of radon exposure: a review.
Radon-222 is a naturally occurring radioactive gas that is responsible for approximately half of the human annual background radiation exposure globally. Chronic exposure to radon and its decay products is estimated to be the second leading cause of lung cancer behind smoking, and links to other forms of neoplasms have been postulated. Ionizing radiation emitted during the radioactive decay of radon and its progeny can induce a variety of cytogenetic effects that can be biologically damaging and result in an increased risk of carcinogenesis. Suggested effects produced as a result of alpha particle exposure from radon include mutations, chromosome aberrations, generation of reactive oxygen species, modification of the cell cycle, up or down regulation of cytokines and the increased production of proteins associated with cell-cycle regulation and carcinogenesis. A number of potential biomarkers of exposure, including translocations at codon 249 of TP53 in addition to HPRT mutations, have been suggested although, in conclusion, the evidence for such hotspots is insufficient. There is also substantial evidence of bystander effects, which may provide complications when calculating risk estimates as a result of exposure, particularly at low doses where cellular responses often appear to deviate from the linear, no-threshold hypothesis. At low doses, effects may also be dependent on cellular conditions as opposed to dose. The cellular and molecular carcinogenic effects of radon exposure have been observed to be both numerous and complex and the elevated chronic exposure of man may therefore pose a significant public health risk that may extend beyond the association with lung carcinogenesis.


REPRODUCTIVE ECOLOGY AND BIOGEOGRAPHY OF INDO-WEST PACIFIC ANGELFISHES (PISCES: POMACANTHIDAE).
Analysis of the relationships between duration of the pelagic larval stage (as indicated by otolith microstructure), adult size, and the extent of geographic distribution for Indo-West Pacific angelfishes (Pomacanthidae) indicates that neither adult size nor larval duration significantly predicts extent of distribution, either individually or jointly in a multiple regression. These results are robust for both the family as a whole and the genus best represented in our data (Centropyge). If larval duration and adult size do have an effect, it is only jointly and at the genus level. However, larval duration and adult size do correlate significantly and negatively with one another. The operational factor seems to be egg size, which correlates positively with adult size, and negatively with duration of the pelagic larval stage. Similar correlations are evident in both marine invertebrates and at least some other coral-reef fishes, suggesting they are of widespread significance. The limited ability of either reproductive parameter to predict extent of species distribution indicates, first, that even in a group as morphologically conservative as the Indo-West Pacific pomacanthids, neither a two-fold difference between species in larval duration nor a two order of magnitude difference in female fecundity markedly affects extant distributions; and secondly, that either undescribed biological factors or historical constraints are of paramount importance. Available evidence suggests that dispersal abilities of most coral reef fishes, in fact, may be limited, despite the nearly universal occurrence of a pelagic stage in development.


Flight initiation by male Rhodnius prolixus is promoted by female odors.
Several triatomine bug species utilize chemical cues for sexual communication. We tested whether female or male Rhodnius prolixus, a vector of Chagas disease, produce volatile chemicals that elicit flight responses from conspecifics, and then isolated the source of the chemical. Males confronted with an airstream containing female odors showed a significantly greater take-off frequency compared to a blank airstream or an airstream with male odors. In contrast, females exhibited similar take-off frequencies to male or female odor as to a clean airstream. Occlusion of female metasternal glands with paraffin wax resulted in a significant decrease in male take-off frequency compared to that of intact females. Additionally, excised female metasternal glands elicited a similar take-off frequency from males as did intact females, both significantly greater than the take-off frequency to clean air. These results show that R. prolixus females release a pheromone from their metasternal glands that causes upwind flight in conspecific males.


The impact of occupational therapy and lifestyle interventions on older persons' health, well-being, and occupational adaptation.
The aim of this study was to investigate whether a four-month occupational based health-promoting programme for older persons living in community dwellings could maintain/improve their general health and well-being. Further, the aim was to explore whether the programme facilitated the older persons' occupational adaptation. The study had a quasi-experimental design, with a non-equivalent control group combined with semi-structured interviews. The intervention group comprised 22 participants, and the control group 18. Outcomes were measured using the Short Form 36, Life Satisfaction Index-Z and Meaningful Activity Participation Assessment. Content analysis, based on concepts from the Model of Occupational Adaptation, was used to analyse the interviews. The intervention group showed statistically significant improvements in general health variables such as vitality and mental health, and positive trends for psychological well-being. There were no statistically significant differences between the intervention group and the control group, but the groups were not fully matched. The qualitative analysis based on Occupational Adaptation pointed out social aspects as a compliment to the overall results. Participating in meaningful, challenging activities in different environments stimulates the occupational adaptation process; this is something occupational therapists could use to empower older persons to find their optimal occupational lives.


Microleakage and Shear Bond Strength of Composite Restorations Under Cycling Conditions.
The aim of this study was to evaluate microleakage and shear bond strength of composite restorations under different cycling conditions. Class V cavities were prepared in the buccal and lingual surfaces of 30 human molars (n=60). A further 60 molars were used to prepare flat enamel and dentin specimens (n=60 each). Cavities and specimens were divided into six groups and pretreated with an adhesive (self-etch/Clearfil SE Bond or etch-and-rinse/Optibond FL). Composite was inserted in the cavities or adhered to the specimens' surfaces, respectively, and submitted to cycling (control: no cycling; thermal cycling: 10,000 cycles, 5°C to 55°C; thermal/erosive cycling: thermal cycling plus storage in hydrochloric acid pH 2.1, 5 minutes, 6×/day, 8 days). Microleakage was quantified by stereomicroscopy in enamel and dentin margins after immersion in silver nitrate. Specimens were submitted to shear bond strength testing. Statistical analysis was done by two-way analysis of variance and Kruskal-Wallis tests (p<0.05). Microleakage in enamel margins was significantly lower in the control group compared with thermal cycling or thermal/erosive cycling. Erosive conditions increased microleakage compared with thermal cycling (significant only for Clearfil SE Bond). No significant differences were observed in dentin margins. Bond strength of enamel specimens was reduced by thermal cycling and thermal/erosive cycling when Clearfil SE Bond was used and only by thermal/erosive cycling when Optibond FL was used. No differences were observed among dentin specimens. Thermal/erosive cycling can adversely affect microleakage and shear bond strength of composite resin bonded to enamel.


Oxytocin resistance in Brattleboro rat adipocytes and comparative studies on insulin or oxytocin responsiveness in normal rat adipocytes.
We have evaluated factors, other than genetic, which might be related to the lack of an oxytocin-mediated insulinlike response (glucose oxidation; lipogenesis) in adipocytes from Brattleboro rats, homozygous for the diabetes insipidus trait (HoDI rats). The manoeuvres used in an attempt to restore the glucoregulatory responses to oxytocin in HoDI cells (increased glucose in the fat pad digestion medium; increased calcium concentration in the oxidation assay; estrogen treatment; use of [1-14C]glucose as substrate; inclusion of adenosine in the assay medium; vasopressin replacement therapy) uniformly failed to result in oxytocin activation of HoDI adipocytes. In contrast, the contractile responses of estrogenized HoDI rat uteri were indistinguishable from those of estrogenized normal rats. We conclude that the nonresponsiveness of the Brattleboro adipocytes to the glucoregulatory actions of oxytocin is not due to factors related to the conditions of the bioassay. On the other hand, in normal fat cells (from Sprague-Dawley and Long Evans rats), oxytocin responsiveness was augmented by a number of the manoeuvres mentioned above, most notably by the inclusion of either calcium (10 mM) or adenosine (10 microM) in the assay medium. Nonetheless, the maximum oxytocin responsiveness of adipocytes from Long Evans or Sprague-Dawley rats, under all conditions of assay, was still only a fraction (less than 20%) of the maximal response to insulin. The effect of adenosine on oxytocin action (increased sensitivity, without an effect on the maximum response) is in keeping with the previously observed effects of this nucleoside on the action of insulin; our results thus pointed to a new parallel in the action of insulin and oxytocin.


A novel 4-base-recognizing RNA cutter that can remove the single 3' terminal nucleotides from RNA molecules.
Mammalian tRNase ZL shows versatility in substrate recognition. This enzyme can not only process pre-tRNAs by cleaving off their 3' trailer sequences, but also recognize and cleave pre-tRNA-like complexes and micro-pre-tRNAs. Here we demonstrate that 24-27 nt hairpin RNAs (hook RNAs) can guide cleavages of separate target RNAs by tRNase ZL through the micro-pre-tRNA-like complexes between the targets and the hook RNAs and that tRNase ZL together with hook RNA works as 4-7-base-recognizing RNA cutters. The cleavage sites were located only after the nucleotide corresponding to the discriminator nucleotide. Cleavage assays for various substrate/hooker complexes showed that the cleavage efficiency changes depending on the maximum number of substrate/hooker recognition base pairings and the stem length of hook RNA and that a 5 nt recognition sequence and a hook RNA containing a 6 or 7 bp stem are the best combination for the optimal target cleavage. We also show that a 4-base RNA cutter can remove the single 3' terminal nucleotides from RNA molecules. These results indicate that this new type of RNA cutter can be utilized to homogenize at their 3' termini RNA transcripts synthesized in vitro with a bacteriophage RNA polymerase.


[Pulmonary manifestations of tuberculosis in childhood].
We mention the major pathogenous characteristics of a tuberculosis infection. Immunity to tuberculosis and tuberculin allergy are connected with each other but are not identical reactions of the organism. We describe the well-known complications in primary infections, namely the primary focus and the formation of lymph nodes. The peripheral primary focus generally regresses after treatment. However, the hilar lymph nodes sometimes increase in size even after appropriate medication (autonomous activity of some lymph nodes). If x-ray films reveal segmental changes and if there is evidence of viral or mycoplasma infection, tuberculosis should be taken into consideration as a parallel disorder because these infections often pave the way for tuberculosis. In the stage of early generalisation miliaria may occur within 3 months of infection. In most cases miliaria escapes detection. Pleurisy involves tuberculosis bacteria entering the pleural cavity. One of the prerequisites of pleurisy is hyperergia of the pleura. If the patient has tuberculotic pleurisy it means that miliaria has already occurred and miliary tuberculosis need not be anticipated. We also mention secondary diffusion into the apex of the lung and its consequences.


Interpreting the results of systematic reviews.
Systematic reviews are increasingly common and often provide the most robust research approach to informed decisions about health care. The successful interpretation of systematic reviews for decisions about health care requires consideration of their quality and judgement on whether the participants and the interventions assessed are applicable to a different setting. This chapter includes a table of questions to help the reader consider this issue. If a review satisfies the requirements of the present setting, the benefits and harms of the interventions, along with other information including patient preferences, will help the clinician decide what the review "means" and what to do about this in practice.


Pharmacovigilance practices for better healthcare delivery: knowledge and attitude study in the national malaria control programme of India.
Objective. With large scale rollout of artemisinin based therapy in the National Malaria Control Programme of India, a risk management plan is needed. This depends on adverse drug reaction (ADR) reporting by the healthcare professionals (HCPs). For the programme to be successful, an understanding of the mindset of HCPs is critical. Hence, the present study was designed to assess and compare the ADR reporting beliefs of HCPs involved in the National Malaria Control Programme of India. Methods. A cross-sectional survey was conducted amongst the HCPs who manage malaria up to the district level in India. A 5-point Likert scale-based questionnaire was developed as a study tool. Results. A total of 154 HCPs participated in the study (age: 42.4 ± 10.1 years with 33.8% being females). About 61% felt that only medically qualified HCPs are responsible for ADR reporting. Likeliness to report in future was mentioned by 45% HCPs. The knowledge score was relatively lower for life science graduates (P = 0.09). Knowledge correlated positively with attitude (r (2) = 0.114; P < 0.0001). Conclusion. Based on the caveats identified, a specific and targeted in-service education with hands-on training on ADR monitoring and reporting needs to be designed to boost real time pharmacovigilance in India.


Intrinsic-water desorption induced thermomechanical response of hydrogels.
We report an interplay between the desorption of intrinsic water and relaxation of polymer chains resulting in an unusual thermomechanical response of a hydrogel, wherein the elastic modulus increases in a certain temperature range followed by a sharp decrease with a further increase in temperature. We establish that, in a hydrogel, the desorption of disparate water types having distinct binding energy affects the consolidation and relaxation behaviour of the matrix, which in turn affects the mechanical properties at different temperature ranges. Using temperature-dependent dielectric relaxation spectroscopy and nanoindentation techniques, the chain dynamics and mechanical properties are investigated.


Intrinsic gray-matter connectivity of the brain in adults with autism spectrum disorder.
Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions that are accompanied by atypical brain connectivity. So far, in vivo evidence for atypical structural brain connectivity in ASD has mainly been based on neuroimaging studies of cortical white matter. However, genetic studies suggest that abnormal connectivity in ASD may also affect neural connections within the cortical gray matter. Such intrinsic gray-matter connections are inherently more difficult to describe in vivo but may be inferred from a variety of surface-based geometric features that can be measured using magnetic resonance imaging. Here, we present a neuroimaging study that examines the intrinsic cortico-cortical connectivity of the brain in ASD using measures of "cortical separation distances" to assess the global and local intrinsic "wiring costs" of the cortex (i.e., estimated length of horizontal connections required to wire the cortex within the cortical sheet). In a sample of 68 adults with ASD and matched controls, we observed significantly reduced intrinsic wiring costs of cortex in ASD, both globally and locally. Differences in global and local wiring cost were predominantly observed in fronto-temporal regions and also significantly predicted the severity of social and repetitive symptoms (respectively). Our study confirms that atypical cortico-cortical "connectivity" in ASD is not restricted to the development of white-matter connections but may also affect the intrinsic gray-matter architecture (and connectivity) within the cortical sheet. Thus, the atypical connectivity of the brain in ASD is complex, affecting both gray and white matter, and forms part of the core neural substrates underlying autistic symptoms.


Diagnostic and prognostic significance of serum apolipoprotein C-I in triple-negative breast cancer based on mass spectrometry.
Women with triple-negative breast cancer (TNBC) have poor prognosis because of the aggressive nature of the tumor, delayed diagnosis and non-specific symptoms in the early stages. Identification of novel specific TNBC serum biomarkers for screening and therapeutic purposes therefore remains an urgent clinical requirement.We obtained serum samples from a total of 380 recruited individuals split into mining and testing sets, with the aim of screening for reliable protein biomarkers from TNBC and non-TNBC (NTNBC) sera. Samples were assessed using mass spectrometry, followed by receiver operating characteristic (ROC), survival and hazard function curve as well as multivariate Cox regression analyses to ascertain the potential of the protein constituents as diagnostic and prognostic biomarkers for TNBC.We identified upregulated apolipoprotein C-I (apoC-I) with a validated positive effect on TNBC tumorigenesis, with confirmation in an independent test set and minimization of systematic bias by pre-analytical parameters. The apoC-I protein had superior diagnostic ability in distinguishing between TNBC and NTNBC cases. Moreover, the protein presented a more robust potential prognostic factor for TNBC than NTNBC. The apoC-I protein identified in this study presents an effective novel diagnostic and prognostic biomarker for TNBC, indicating that measurement of the peak intensity at 7785 Da in serum samples could facilitate improved early detection and estimation of postoperative survival prognosis for TNBC.


Von Willebrand factor (VIII R:Ag), fibronectin, and insulin-like growth factors I and II in diabetic retinopathy and nephropathy.
We have measured plasma von Willebrand factor (VWF) as the factor VIII-related antigen, plasma fibronectin, and two of the serum somatomedins, insulin-like growth factor I (IGF I) and IGF II, in 51 diabetic patients and 25 nondiabetic control subjects. VWF was significantly higher in the diabetic group than in the controls (173 +/- 9% SEM versus 101 +/- 9%, P less than 0.001), as has been reported by others. However, within the diabetic group there was no significant difference in VWF between those patients without retinopathy, those with background or proliferative retinopathy, or those with macular edema. There was also no difference in VWF between the diabetic subjects with and those without proteinuria. These results rule against a previously advanced hypothesis that the increase in VWF in patients with diabetes is secondary to microangiopathy. No significant difference was observed in fibronectin, IGF I, or IGF II between the diabetic and control groups, between the diabetic group without retinopathy and the retinopathic subgroups, and between the diabetic subjects with and without proteinuria. In the diabetic patients, there was no correlation between diabetic control as assessed by glycosylated hemoglobin and glycosylated serum protein, and the plasma levels of VWF, fibronectin, IGF I, or IGF II. The results of this study strongly suggest that neither plasma VWF, fibronectin, IGF I, nor IGF II plays an important primary role in the pathogenesis of diabetic microvascular disease, although one or more of these factors might play a permissive role.


Historical Perspectives on Core-Carrier Gutta-Percha Obturation.
Dr. William Ben Johnson introduced the contemporary use fo core-carrier technology for root canal obturation in the late 1970s. This technology has undergone multiple enhancements since its commercial introduction in the early 1990s and has provided a unique clinical treatment regimen for clinicians globally. However, the very roots and evolution of this technique can be traced to the later 1800s, exhibiting a torturous and fragmented history until Dr. Johnson's creativity and impetus brought it the the forefront of root canal obturation techniques. Dr. Johnson received the Inventor of the Year award in Oklahoma for these innovative accomplishments.


Hand position modulates saccadic activity in the frontal eye field.
Recent neurophysiological studies have begun to uncover the neuronal correlates of eye hand coordination. This study was designed to test whether the frontal eye field (FEF) saccadic activity is modulated by hand position. Single neurons were recorded in two macaque monkeys performing visually guided saccades while holding their hand at given locations on a touchscreen. To determine the relative contributions of hand vision and its proprioception, monkeys executed the task with or without vision of the hand. We found that saccadic activity of more than half of the neuronal sample (54%; n=130) was dependent on hand position relative to the saccade end point. Both visual and proprioceptive signals contributed to this modulation. These data demonstrate that the oculomotor function of the FEF takes into account hand position in space.


Downregulation of miR-222 Induces Apoptosis and Cellular Migration in Adenoid Cystic Carcinoma Cells.
Previous studies have shown that miR-222 targets the p53 upregulated modulator of apoptosis (PUMA) to regulate cell biological behavior in some human malignancies. We hypothesized that there was a negative regulation, which might induce apoptosis, between miR-222 and PUMA in adenoid cystic carcinoma (ACC). In this study, the expression levels of miR-222 and the PUMA gene after transfection with antisense miR-222 (As-miR-222) were evaluated by RT-PCR and Western blot assays. Cell proliferation and migratory abilities were detected by CCK-8 and Transwell assays. Cell cycle and apoptosis were analyzed by flow cytometry. Our results showed that, when compared with the control and scramble-transfected groups, the expression of miR-222 in the As-miR-222 group was downregulated, while the expression of PUMA at both mRNA and protein levels was upregulated, cell proliferation and migratory abilities were inhibited, and apoptosis was increased. Our results suggested that As-miR-222 transfection could upregulate the expression of PUMA to induce apoptosis in ACC, providing a new concept for the treatment of ACC.


Avocado Pear Pulp (Persea americana)-Supplemented Cake Improved Some Serum Lipid Profile and Plasma Protein in Rats.
Avocado pear pulp (Persea americana) is indigenous to Mexico. It is widely cultivated and consumed all over the world. Its oil is rich in monounsaturated fatty acids (SFAs) and can be used to replace SFAs in a diet to lower low-density lipoprotein (LDL) and raise high-density lipoprotein (HDL). Consumers seek healthy foods that aid in reducing metabolic syndrome. The aim of this study is to evaluate the effects of the best acceptable cakes supplemented with 0%, 10%, 30%, and 50% avocado on the serum lipid profile and plasma protein in rats. Twenty-five rats separated into five groups of four test groups and one control group were fed individually for 14 days, after which blood samples were withdrawn and subjected to biochemical analysis. Intake of cake supplemented with avocado pear pulp resulted in significant (P < .05) increment in the body weight, total cholesterol, triglycerides and HDL, and serum protein and decrement in LDL of the rats. The group fed 50% supplemented cake showed highest increase in HDL and least decrease in LDL. Cake supplemented with 50% avocado pear pulp proved to be a better supplementation in reducing serum LDL and increasing serum HDL and serum protein in rats, indicating to be a promising nutraceutical for the management of cardiovascular diseases and its associated complications.


Preferences for choice across adulthood: age trajectories and potential mechanisms.
Across a variety of decision domains, older adults were found to desire fewer choice options than younger adults, but the age trajectory and underlying mechanisms of these effects remain unknown. The present study examined the pattern and correlates of age differences in choice set size preferences using self-report and behavioral measures. Self-reported choice set size preferences were assessed in a large-scale survey using an adult life span sample (N = 318, ages 18-90 years). A subset of younger and older adults (n = 109) also completed behavioral measures of choice preferences and information seeking. Based on prior research and theorizing on aging and decision making, we tested for a variety of possible covariates, including maximizing and decision-making self-efficacy. Combined results indicated that the age trend of choice set size preferences is linear, gradual, and domain-general. Findings also indicated a significant association between choice preferences and the extent of predecisional information search. Although age differences were evident in both self-report and behavioral measures, they were not explained by any of the covariates tested. We discuss the implications of these findings for research on aging and decision making, as well as public policy.


Implications of hedgehog signaling antagonists for cancer therapy.
The hedgehog (Hh) pathway, initially discovered in Drosophila by two Nobel laureates, Dr. Eric Wieschaus and Dr. Christiane Nusslein-Volhard, is a major regulator for cell differentiation, tissue polarity and cell proliferation. Studies from many laboratories, including ours, reveal activation of this pathway in most basal cell carcinomas and in approximately 30% of extracutaneous human cancers, including medulloblastomas, gastrointestinal, lung, breast and prostate cancers. Thus, it is believed that targeted inhibition of Hh signaling may be effective in treating and preventing many types of human cancers. Even more exciting is the discovery and synthesis of specific signaling antagonists for the Hh pathway, which have significant clinical implications in novel cancer therapeutics. This review discusses the major advances in the current understanding of Hh signaling activation in different types of human cancers, the molecular basis of Hh signaling activation, the major antagonists for Hh signaling inhibition and their potential clinical application in human cancer therapy.


[The valves of the marginal sinus of the lymph nodes].
Popliteal lymph nodes of male Wistar rats were studied in scanning regime of electron microscope. On the base of the data obtained it is concluded that on the lymph node surface and in the thickness of a capsule afferent lymphatic vessels branch into thin rami supplied with valves from the inside of the capsule in the site of falling into marginal sinus. Valvular apparatus found obviously gives possibility to regulate lymph flow in the lymph node.


Augmented Reality Driven Steady-State Visual Evoked Potentials for Wheelchair Navigation.
Medically oriented Brain Computer Interfaces (BCIs) have been proposed as a promising approach addressed to individuals suffering from severe paralysis. Steady-State Visual Evoked Potentials (SSVEPs) in particular have been proven successful in many different applications, achieving high information throughput with short or even no training. However, efficient electric wheelchair navigation combining high accuracy and comfort is still not demonstrated. In this paper, we propose the use of an SSVEP-based universal control system featuring augmented reality (AR) glasses in an attempt to increase ease of use and patient acceptability without making compromises on BCI performance. The system received positive user-feedback, reaching a mean accuracy of 90%. Merits and pitfalls of the system proposed are also addressed.


Male Breast Cancer: 20 Years Experience of a Tertiary Hospital from the Middle Black Sea Region of Turkey.
Male breast cancer is a rare neoplasm, and its treatments are based on those of female breast cancer. This study aimed to analyze 20 years of male breast cancer clinical characteristics and treatment results from the Middle Black Sea Region of Turkey. A retrospective analysis of 16 male breast cancer patients treated in our tertiary hospital between 1994 and 2014 was performed. Epidemiologic data, tumor characteristics, and treatments were recorded and compared with 466 female breast cancer ((premenopausal; n=230)+(postmenopausal n=236)) patients. The 5-year disease-free and overall survival rates were calculated. Male breast cancer constituted 0.1% of all malignant neoplasms in both sexes, 0.2% of all malignant neoplasms in males, and 0.7% of all breast cancers. The mean patient age in this study was 59.8±9.5 (39-74) years. The mean time between first symptom and diagnosis was 32.4±5.3 (3-60) months. Histology revealed infiltrative ductal carcinoma in 81.3% of patients. The most common detected molecular subtype was luminal A, in 12 (75%) patients. Estrogen receptor rate (93.8%) in male breast cancer patients was significantly higher than that in female breast cancer (70.8% in all females, p=0.003; 68.2% in postmenopausal females, p=0.002) patients. Most of the tumors (56.3%) were grade 2. Tumor stage was T4 in 50% of males. The majority (56.3%) of the patients were stage III at diagnosis. Surgery, chemotherapy, radiotherapy and endocrine-therapy were applied to 62.5%, 62.5%, 81.2% and 73.3%, respectively. Loco-regional failure did not occur in any of the cases. All recurrences were metastastic. The 5-year disease-free and overall survival rates in male breast cancer patients were 58% and 68%, respectively. Tumors found in male breast cancer patients were similar in size to tumors found in females, but they advanced to T4 stage more rapidly because of the lack of breast parenchymal tissues. The rate of estrogen receptor expression tended to be higher in male breast cancer patients than in female breast cancer patients. Metastasis is the most important problem in initially non-metastatic male breast cancer patients.


Upregulated energy metabolism in the Drosophila mushroom body is the trigger for long-term memory.
Efficient energy use has constrained the evolution of nervous systems. However, it is unresolved whether energy metabolism may resultantly regulate major brain functions. Our observation that Drosophila flies double their sucrose intake at an early stage of long-term memory formation initiated the investigation of how energy metabolism intervenes in this process. Cellular-resolution imaging of energy metabolism reveals a concurrent elevation of energy consumption in neurons of the mushroom body, the fly's major memory centre. Strikingly, upregulation of mushroom body energy flux is both necessary and sufficient to drive long-term memory formation. This effect is triggered by a specific pair of dopaminergic neurons afferent to the mushroom bodies, via the D5-like DAMB dopamine receptor. Hence, dopamine signalling mediates an energy switch in the mushroom body that controls long-term memory encoding. Our data thus point to an instructional role for energy flux in the execution of demanding higher brain functions.


Intracerebroventricular Administration of 192IgG-Saporin Alters Expression of Microglia-Associated Genes in the Dorsal But Not Ventral Hippocampus.
One of important aspects of development of Alzheimer's disease is degeneration of septal cholinergic neurons that innervate the hippocampus. We took advantage of widely used model of cholinergic deficit in the hippocampus, intracerebroventricular administration of 192IgG-saporin (Ig-saporin), to analyze the postponed consequences of cholinergic deficit in different parts of the hippocampus. We studied effects of the immunotoxin on the behavior of rats and gene expression in the dorsal and ventral hippocampus using RNA-seq approach. We found that under normal conditions dorsal and ventral parts of the hippocampus differ in the expression of 1129 protein-coding genes and 49 non-coding RNAs (ncRNAs) and do not differ in the expression of 10 microRNAs, which were detected in both parts of the hippocampus. Ig-saporin-induced degeneration of cholinergic septal neurons did not affect rat behavior in open field, T-maze, and passive avoidance task but impaired memory retention in Morris water maze. To analyze 192Ig-saporin-induced changes in the gene expression, we formed the following groups of genes: genes expressed exclusively in certain cell types (neurons, astrocytes, microglia, oligodendrocytes, and vascular cells) and, among universally expressed genes, a group of genes that encode ribosome-forming proteins. For all groups of genes, the alterations in the gene expression produced by the immunotoxin were stronger in the dorsal as compared to the ventral hippocampus. We found that, among groups of universally expressed genes, Ig-saporin increased the expression of ribosome-forming proteins in both dorsal and ventral hippocampus. Ig-saporin also strongly upregulated expression of microglia-specific genes only in the dorsal hippocampus. A subset of affected microglial genes comprised genes associated with inflammation, however, did not include genes related to acute inflammation such as interleukins-1b, -6, -15, and -18 as well as TNF. The expression of other cell-specific genes (genes specific for neurons, astrocytes, oligodendrocytes, and vascular cells) was unaffected. The data obtained suggest that disturbance of memory-associated behavior after administration of Ig-saporin is associated with upregulation of microglia-associated genes in the dorsal but not ventral hippocampus.


Antibacterial activity of the stem bark of Tieghemella Heckelii Pierre ex. A Chev against methicillin-resistant Staphylococcus aureus.
Tieghemella heckelii (Sapotaceae) is a medicinal plant used in Africa, particularly in Côte d'Ivoire for treating various diseases including infections. Identification of prospective antibacterial compounds from stem bark of this plant as a result of its medicinal virtue, led to screening activity against methicillin resistant bacteria. Six extracts (hexane, chloroform, ethyl acetate, ethanol, methanol and sterile distilled water) were prepared and tested on methicillin resistant Staphylococcus aureus (MRSA) using broth microdilution method for activity assessment. From this experiment, the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of the plant extracts were determined in sterile 96-well microplates in order to search for both bacteriostatic and bactericidal effects. Afterwards, data analysis was performed using GraphPad Prism5 software (One-way ANOVA and Turkey Multiple Comparison test). The results were then presented as Mean ± SD for experiment repeated three times. Four extracts (ethyl acetate, methanol, ethanol and sterile distilled water) showed credible potency, with strong, significant, and moderate growth inhibition of the MRSA tested. The MIC values which varied from 45 μg/mL to 97 μg/mL according to microbial phenotype, resolutely established the activity of the plant extracts. Additionally, the MBC values which varied, depending on the type of bacteria strain, revealed the bacteriostatic and bactericidal effects of the active extracts against Methicillin-resistant Staphylococcus aureus. The present study is a confirmation of the therapeutic potential of Tieghemella heckelii and its promising contribution to the discovery of a novel antibacterial drug pertaining to these resistant strains.


Pathways of acetone's metabolism in the rat.
Distributions of 14C were different from those of 13C in glucoses formed by livers of rats in diabetic ketosis and perfused with [2-14C]acetone and [2-13C]lactate. There was 32-73% of the 14C and 8-12% of the 13C in carbons 3 and 4 of the glucoses with the remaining 14C and 13C distributed about equally in the other carbons. Incorporations of 14C from [2-14C]acetone (14-39%) also exceeded those from [2-14C]pyruvate (8-10%) into carbons 3 and 4 of glucoses formed by hepatocytes from rats fed acetone or fasted. [2-14C]Acetone and [2-14C]pyruvate were infused into rats that were fed, fasted, given acetone in their drinking water, or in diabetic ketosis. Thirty-seven to 52% of the 14C in the glucoses formed was in their carbons 3 and 4 when the acetone was infused and 8 to 14% when the pyruvate was infused. [1,3-14C]Hydroxybutyrate was formed by the rats in diabetic ketosis given [2-14C]acetone. It is concluded that acetone is metabolized in rats to a large extent by a pathway in which lactate or its metabolic equivalent is not an intermediate and that pathway is via acetyl-CoA. via acetyl-CoA.


Atrazine and terbutryn degradation in deposits from groundwater environment within the boreal region in Lahti, Finland.
The degradation of pesticides atrazine and terbutryn was investigated under aerobic and anaerobic conditions in the northern boreal region subsurface deposits and sterilized controls from the depths of 6.3-21.0 m below the surface and 1.2-16.9 m below the groundwater table. During 1.3-1.7 years of laboratory incubation, atrazine degradation under aerobic conditions varied from rapid (half-live 38 days) to no degradation. Anaerobically, atrazine half-lives were 430-829 days. Organic matter, nitrogen, and lead in deposits correlated positively with the atrazine concentration in groundwater. Aerobic and anaerobic terbutryn half-lives were 193-644 and 266-400 days, respectively. Microbial aerobic atrazine and terbutryn degradation was confirmed in the deep deposits near the water table. Under aerobic conditions, the high amounts of Cr, Mn, Ni, and Zn in deposits decreased the chemical degradation of terbutryn.


Numerical simulation of wave propagation in a realistic model of the human external ear.
In this study, a numerical investigation is performed to evaluate the effects of high-pressure sinusoidal and blast wave's propagation around and inside of a human external ear. A series of computed tomography images are used to reconstruct a realistic three-dimensional (3D) model of a human ear canal and the auricle. The airflow field is then computed by solving the governing differential equations in the time domain using a computational fluid dynamics software. An unsteady algorithm is used to obtain the high-pressure wave propagation throughout the ear canal which is validated against the available analytical and numerical data in literature. The effects of frequency, wave shape, and the auricle on pressure distribution are then evaluated and discussed. The results clearly indicate that the frequency plays a key role on pressure distribution within the ear canal. At 4 kHz frequency, the pressure magnitude is much more amplified within the ear canal than the frequencies of 2 and 6 kHz, for the incident wave angle of 90° investigated in this study, attributable to the '4-kHz notch' in patients with noise-induced hearing loss. According to the results, the pressure distribution patterns at the ear canal are very similar for both sinusoidal pressure waveform with the frequency of 2 kHz and blast wave. The ratio of the peak pressure value at the eardrum to that at the canal entrance increases from about 8% to 30% as the peak pressure value of the blast wave increases from 5 to 100 kPa for the incident wave angle of 90° investigated in this study. Furthermore, incorporation of the auricle to the ear canal model is associated with centerline pressure magnitudes of about 50% and 7% more than those of the ear canal model without the auricle throughout the ear canal for sinusoidal and blast waves, respectively, without any significant effect on pressure distribution pattern along the ear canal for the incident wave angle of 90° investigated in this study.


[Levels of serum cholesterol in a catalan population. Evolution over a 6- year period (1994-1996)].
To study the evolution of the serum levels of cholesterol in a population over 6 years. Design. cross-sectional observational study.Setting. Primary and specialist care in the county of Osona (Barcelona). Study of those patients attending for health consultations in the county, whether at primary or hospital level, and who had their cholesterol level determined. The levels of serum cholesterol of the 7882 patients studied during September to December 1994 was compared with those of the 10 319 patients analysed during the same months of 1999. The mean levels of cholesterol increased steadily in both sexes with age, up to the fifth or sixth decade of life, at which point a slow descent started. Cholesterolaemia was higher in men than in women in the third and fourth decades of life; but from this age on, mean levels are higher in women than in men. Cholesterol levels in both sexes were higher in the 1999 period studied than in 1994. During 1999, 52.7% of men and 52.3% of women had serum cholesterol levels above 200 mg/dL, whereas in 1994 these figures were 49.1% and 49.2%, respectively. Mean levels of serum cholesterol in the population under study are high and increased between the two sampling years. Preventive and hygiene-diet measures need to be fomented among the general population in order to improve control of cholesterolaemia.


Structure-based engineering of strictosidine synthase: auxiliary for alkaloid libraries.
The highly substrate-specific strictosidine synthase (EC 18.104.22.168) catalyzes the biological Pictet-Spengler condensation between tryptamine and secologanin, leading to the synthesis of about 2000 monoterpenoid indole alkaloids in higher plants. The crystal structure of Rauvolfia serpentina strictosidine synthase (STR1) in complex with strictosidine has been elucidated here, allowing the rational site-directed mutation of the active center of STR1 and resulting in modulation of its substrate acceptance. Here, we report on the rational redesign of STR1 by generation of a Val208Ala mutant, further describing the influence on substrate acceptance and the enzyme-catalyzed synthesis of 10-methyl- and 10-methoxystrictosidines. Based on the addition of strictosidine to a crude strictosidine glucosidase preparation from Catharanthus cells, a combined chemoenzymatic approach to generating large alkaloid libraries for future pharmacological screenings is presented.


Patient-reported outcomes in head and neck cancer: prospective multi-institutional patient-reported toxicity.
Head and neck cancer is occurring in an increasingly younger patient population, with treatment toxicity that can cause significant morbidity. Using a patient guided, Internet-based survivorship care plan program, we obtained and looked at patterns of patient-reported outcomes data from survivors seeking information after treatment for head and neck cancer. The Internet-based OncoLife and LIVESTRONG Care Plan programs were employed, which design unique survivorship care plans based on patient-reported data. Care plans created for survivors of head and neck cancer were used in this evaluation. Demographics, treatment modality, and toxicity were included in this evaluation. Toxicity was further analyzed, grouped into system-based subsets. A total of 602 care plans were created from self-identified head and neck cancer survivors, from which patient-reported outcome data were attained. A majority of patients were Caucasian (96.2%) with median age at diagnosis of 55 years, living in suburban locations (39.9%), with ~50% receiving care within 20 miles of their residence. There was an equal distribution of education levels from high school only to graduate school. The majority of patients received care through cancer centers (96.7%), with a split between academic and non-academic centers. Ninety-three percent of patients had radiation therapy as part of their treatment modality, with 70.3% having chemotherapy and 60.1% having surgery. The most common system toxicities affected the oropharynx, followed by epithelium (skin/hair/nail), and then general global health. Specifically, the most common side effects were difficulty swallowing (61.5%) and changes in skin color/texture (49.7%). One third of patients experienced hearing/tinnitus/vertigo, xerostomia, loss of tissue flexibility, or fatigue. The current work demonstrates the ability to obtain patient-reported outcomes of head and neck cancer survivors through an Internet-based survivorship care plan program. For this group dysphagia and dermatitis were the most commonly reported toxicities, as was expected; however, global effects of therapy, such as fatigue, were also significant and should be addressed in future survivorship planning.


Expression of factors and key components associated with the PI3K signaling pathway in colon cancer.
The pathophysiology of colorectal cancer (CRC) has not been fully elucidated. The dysregulation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway frequently contributes to the tumorigenesis and progression of human cancer. The aim of the present study was to explore the expression and clinical significance of a number of associated factors and key components of the PI3K signaling pathway, including phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (p110α), phosphorylated protein kinase B (p-Akt) Ser473, p-mammalian target of rapamycin (mTOR) Ser2448, cyclin D1, cyclin dependent kinase (CDK)4, RELA proto-oncogene, nuclear factor-κβ subunit (p65), Ras and extracellular signal-regulated kinase (ERK)1/2 in human CRC. The expression of target proteins was detected using immunohistochemistry (IHC) in 65 CRC cases and 15 colonic adenoma cases. The association between the expression of target proteins and clinical pathological parameters was analyzed using a χ2 test. IHC results revealed that the expression of all target proteins was significantly increased in CRC tissues compared with in colonic adenoma tissues (P<0.05). No significant associations were observed between the expression of p110α, p-Akt Ser473, p-mTOR Ser2448 and sex, age, differentiation, lymph node metastasis or Tumor-Node-Metastasis staging (P>0.05). Cyclin D1, CDK4 and Ras were revealed to be expressed significantly higher in poorly differentiated CRC compared with moderately differentiated CRC (P<0.05). Expression of p65 and ERK1/2 were significantly increased in cancer tissues with lymph node metastasis compared with cancer tissues without lymph node metastasis (P<0.05). These results suggest that the target proteins may all participate in the tumorigenesis of CRC. Furthermore, cyclin D1, CDK4, Ras, p65 and ERK1/2 may be important in the progression of CRC. The results of the present study may provide novel predictive factors and therapeutic targets for CRC.


Universal labeling chemistry for nucleic acid detection on DNA-arrays.
We show here a new and efficient aqueous chemistry for labeling of any class of nucleic acids for their detection on DNA chip. The labels contain a diazo function as reactive moiety and biotin as detectable unit. The highly selective reaction of diazo group on the phosphate does not disrupt base pairing recognition and hybridization specificity.