Proliferation of carcinogen-damaged hepatocytes during cell-cycle-dependent initiation of hepatocarcinogenesis in the rat.
Hepatocyte proliferation and damage to DNA were characterized during the initiation phase of carcinogenesis in livers of rats that had received a single administration of the methylating agent methyl(acetoxymethyl)nitrosamine (DMN-OAc). Quiescent non-proliferating hepatocytes in intact livers did not appear to be susceptible to initiation by DMN-OAc, whereas proliferating hepatocytes in the S phase appeared to have greatest risk. To characterize the phenomenology of S-phase-dependent initiation further, the fractions of hepatocytes in the S and M phases of the cell cycle were enumerated at various times after treatment with DMN-OAc. Hepatocytes treated when in G1 experienced a delay of up to 20 h in the onset of S phase and a reduced rate of entry into the S and M cycle phases. Hepatocytes treated when in S phase experienced considerable delay in progression to mitosis due to part to inhibition of DNA replication. Hepatocytes treated when in late S/G2 also demonstrated a delay in progression into mitosis. The levels of 7-methylguanine and O6-methyldeoxyguanosine were quantified in the nuclear DNA of proliferating hepatocytes. The kinetics of removal of these lesions appeared to be first-order (half-life = 24 h). Hepatocyte risk of initiation was modeled by a function which summed over time the product of the fraction of hepatocytes in the S phase and the fraction of residual, unrepaired damage to DNA. For hepatocytes treated when in early G1, the time-weighted frequency of premutagenic DNA damage that was present during DNA replication was estimated to be less than half of that for hepatocytes treated when in early S. The results suggest that cell-cycle-dependent variation in sensitivity to initiation of hepatocarcinogenesis may be, in part, due to efficient removal of potentially carcinogenic lesions from DNA during an extended G1. The apparent high sensitivity of hepatocytes in late S/G2 suggests the contribution of additional factors.


Intestinal expression of apolipoprotein A-IV and C-III is coordinately regulated by dietary lipid in newborn swine.
The purpose of this study was to determine the effects of dietary fatty acids on intestinal apolipoprotein (apo) A-IV and C-III expression in the newborn piglet. Two-day-old female piglets received one of three isocaloric formulas containing medium-chain triglycerides (TG) (MCT), intermediate-chain saturated TG (ICST), or long-chain polyunsaturated TG (LCPUT) by continuous duodenal infusion for 24 hrs. Control groups received a low-TG elemental formula infusion (LTG group) and a high-TG long-chain unsaturated lipid emulsion infusion (HTG group). Jejunal synthesis of both apo A-IV and C-III was increased by all infusions compared to the LTG group. Apo A-IV and C-III mRNA levels paralleled synthesis levels except for apo C-III with the MCT diet, where regulation appeared to occur at the translational level. Among all groups, apo A-IV synthesis and mRNA abundance were linearly correlated with that of apo C-III.


Surgical stapling for repair of a rectal tear in a horse.
A grade-4 rectal tear in a mare was successfully repaired per rectum, using a surgical stapling device. The mare had only minor postoperative complications. This technique has some advantages over previously described procedures, but should be reserved for use in selected cases.


Formation of early and advanced Maillard reaction products correlates to the ripening of cheese.
The present study deals with the characterization of the ripening of cheese. A traditional German acid curd cheese was ripened under defined conditions at elevated temperature, and protein and amino acid modifications were investigated. Degree of proteolysis and analysis of early [Amadori compound furosine (6)] and advanced [N(ε)-carboxymethyllysine (4), N(ε)-carboxyethyllysine (5)] Maillard reaction products confirmed the maturation to proceed from the rind to the core of the cheese. Whereas 6 was decreased, 4 and 5 increased over time. Deeper insight into the Maillard reaction during the ripening of cheese was achieved by the determination of selected α-dicarbonyl compounds. Especially methylglyoxal (2) showed a characteristic behavior during storage of the acid curd cheese. Decrease of this reactive structure was directly correlated to the formation of 5. To extend the results of experimental ripening to commercial cheeses, different aged Gouda types were investigated. Maturation times of the samples ranged from 6 to 8 weeks (young) to more than 1 year (aged). Again, increase of 5 and decrease of 2 were able to describe the ripening of this rennet coagulated cheese. Therefore, both chemical parameters are potent markers to characterize the degree of maturation, independent of coagulation.


Observations of highly localized oscillons with multiple crests and troughs.
Two types of stable, highly localized Faraday resonant standing waves with multiple crests and troughs are observed in an ethanol-water solution partly filled in a Hele-Shaw cell vertically oscillated with a single frequency. Systematical experiments are performed to investigate the properties of these oscillons. It is found that the wave height of these oscillons is independent of fluid depth from 1 to 5 cm. In particular, some experiments are performed to indicate the high localization of the oscillons, which suggests that these oscillons may be regarded as a combination of the two elementary oscillons discovered by Rajchenbach et al. [Phys. Rev. Lett. 107, 024502 (2011)], for instance, (2,3)=(1,1)+(1,2), where (m,n) denotes an oscillon with m crests and n troughs. So, our experiments also reveal an elegant "arithmetic" of these oscillons. These experimental phenomena are helpful to deepen and enrich our understanding about Faraday waves.


Regina v. Salford Health Authority, Ex Parte Janaway, 12 February 1987.
The applicant was a receptionist for a health centre who refused to type letters for physicians referring patients for abortions. She challenged her dismissal by the health centre, arguing that she was legally authorized to refuse to type abortion referral letters by Section 4(1) of the Abortion Act 1967, which provides that no person may be required to "participate in any treatment authorized by this Act to which he has a conscientious objection." The Court rejected her argument, holding that the treatment to which the Act referred was medical treatment related to abortion and that she had no part in such treatment.


Can Biomimetic Zinc Compounds Assist a (3 + 2) Cycloaddition Reaction? A Theoretical Perspective.
Compounds bearing tetrazole rings are valuable facets in numerous branches of chemistry including metabolic imaging and the production of drugs and high-energy materials. Synthesis of tetrazoles with the help of organocatalysts has intensively been explored, while enzyme-directed click chemistry has attracted less attention and was only used in inhibitor design so far. Herein, we have investigated the possibility of a biomimetic catalyst based on a Lewis acid approach by exploring the anionic cycloaddition of azide and acetonitrile catalyzed by ZnBr2 in comparison with different biomimetic Zn(II) models. Density functional based calculations in the gas phase and with implicit solvation indicate that a variety of bioinspired zinc complexes should be able to catalyze tetrazole formation with catalytic enhancements comparable to zinc bromide salts. Such bioinspired routes could provide new possibilities for the stereo- and regioselectively controlled synthesis of tetrazoles.


A review of dietary polyphenol-plasma protein interactions: characterization, influence on the bioactivity, and structure-affinity relationship.
The interactions between polyphenols, especially flavonoids and plasma proteins, have attracted great interest among researchers. Few papers, however, have focused on the structure-affinity relationship of polyphenols on their affinities for plasma proteins. The aim of this review is to give an overview of the research reports on the characterization, influence on the bioactivity, and the structure-affinity relationship for studying the affinities between polyphenols and plasma proteins. The molecular properties that influence the affinities of polyphenols for plasma proteins are the following: 1) One or more hydroxyl groups in the B-ring (e.g., 3',4' dihydroxylated B ring catechol group) of flavonoids enhanced the binding affinities to proteins. However, the hydroxyl group in the C-ring will weaken the binding interaction. 2) The presence of an unsaturated 2,3-bond in conjugation with a 4-carbonyl group, characteristic of flavonols structure, has been associated with stronger binding affinity with plasma proteins; 3) The glycosylation of flavonoids decreases the affinities for plasma proteins by 1-3 orders of magnitude depending on the conjugation site and the class of sugar moiety; 4) The methylation of hydroxyl groups in flavonoids slightly enhanced the affinities for plasma proteins by 2-16 times; 5) The galloylated catechins have higher binding affinities for plasma proteins than do non-galloylated catechins and the pyrogallol-type catechins have higher affinities than do the catechol-type catechins. The affinity of the catechin with 2,3-trans structure was lower than those of the catechin with 2,3-cis structure; 6) The gallotannins with more gallol groups presented a much higher percentage of binding to plasma proteins. α-D-Gallotannin showed a greater affinity for plasma proteins than does the natural stereoisomer, β-D-gallotannin; 7) The binding degree of chlorogenic acid with only one caffeoyl group was lower than the binding degrees of caffeoyl quinic acids with more caffeoyl groups. The methylation of phenolic acid decreased the affinity for BSA.


Community disruption in small biogenic habitats: A coastal invader overcomes habitat complexity to alter community structure.
Non-indigenous species are often identified as threats to native species and communities. Yet, the mechanisms that enable many of these invaders to thrive and alter their newly invaded habitats are still not fully understood. This applies to habitats such as widespread sedimentary shorelines characterized by the presence of scattered biogenic clumps of blue mussels (Mytilus edulis) structurally more complex than bare sediments. In Atlantic Canada, some of these shorelines are numerically dominated by native mud crabs (Dyspanopeus sayi) but have been gradually invaded by the European green crab (Carcinus maenas). This study describes between-habitat (mussel clump vs. bare sediment) differences in density and diversity of invertebrates. It also tests the impact of juvenile green crabs in comparison to native mud crabs using two approaches: First, measuring habitat-related differences in these crabs' feeding rates on a common prey (soft-shell clams, Mya arenaria). Second, measuring their influence on invertebrate communities associated with mussel clumps. The results show that mussel clumps hold higher invertebrate density and diversity than surrounding sedimentary bottoms. In the laboratory, the feeding rates of native mud crabs were dependent on the type of habitat (sand flat > mussel clump), whereas those of green crabs were significantly higher and unrelated to the habitat in which predation occurred. In field experiments, juvenile green crabs were also the only predators that changed community structure in the mussel clump habitat. These results indicate that green crabs can cause a significant impact on native species and communities. Moreover, they suggest that the ability of this species to overcome the refuge provided by complex biogenic habitats for prey may represent an unexplored mechanism to explain this invader's expansion here and elsewhere.


Taylor and Gradient Descent-Based Actor Critic Neural Network for the Classification of Privacy Preserved Medical Data.
Classification of the privacy preserved medical data is the domain of the researchers as it stirs the importance behind hiding the sensitive data from the third-party authenticator. Ensuring the privacy of the medical records and using the disease prediction mechanisms played a remarkable role in peoples' lives such that the earlier detection of the diseases is required for earlier diagnosis. Accordingly, this article proposes a method, named Taylor gradient descent (TGD)-based actor critic neural network (ACNN), which concentrates on performing the medical data classification. Initially, the privacy of the medical data is ensured by using the key matrix developed based on the privacy utility coefficient matrix using the chronological-Whale optimization algorithm. The privacy protected data are subjected to classification by using ACNN that performs the optimal classification using the proposed TGD algorithm. The proposed TGD algorithm is the integration of Taylor series in the gradient descent algorithm that updates the optimal weight of ACNN based on the weights in the previous iterations. The analysis using the Cleveland, Switzerland, and Hungarian dataset proves that the proposed classification strategy obtains an accuracy of 0.9252, a sensitivity of 0.8419, and a specificity of 0.8387, respectively.


Range of validity of drop shape techniques for surface tension measurement.
Drop shape techniques are widely used for surface tension measurement. As the shape becomes close to spherical, the performance of drop shape techniques deteriorates. A quantitative criterion called shape parameter was previously introduced to quantify the meaning of "well-deformed" drops and "close to spherical" drops. In this paper, a modified definition of the shape parameter that does not depend on the radius of curvature at the drop apex is proposed. Such definition is applicable to different constellations of pendant and sessile drops/bubbles. Dimensional analysis is used to describe similarity in constrained sessile drop shapes and to express the problem using appropriate dimensionless groups. The proposed shape parameter is found to depend only on two dimensionless groups: the dimensionless volume (drop volume normalized by the cube of the holder radius) and the Bond number (using the drop holder's radius as the length scale). A critical shape parameter (minimum value of the shape parameter that guarantees a specified accuracy) is shown to depend only on Bond number. A set of experiments were performed with pure liquids to illustrate the change of the critical shape parameter with the Bond number.


Polyp Resection and Removal Procedures: Insights From the 2017 Digestive Disease Week.
Colorectal cancer (CRC) is an important public health issue not only because of its high incidence but also for its high mortality rate. When CRC is diagnosed at an early stage, the 5-year relative survival rate reaches 89.9%. However, only 39% of patients with CRC are diagnosed at this stage. Screening decreases both the incidence of CRC and the number of CRC-related deaths. There are several options available for screening, and colonoscopy is one of the most common methods utilized in the United States. Screening colonoscopy is associated with durable protection from CRC. However, it has become increasingly apparent in recent years that polyp detection and resection have not been completely effective in clinical practice. Because the protective benefit of colonoscopy is variable, quality benchmarks have been established to improve its clinical effectiveness. The adenoma detection rate (ADR) directly correlates with the incidence and mortality of postcolonoscopy (or interval) CRCs. It is now routine to remove large polyps (≥20 mm) using advanced techniques for endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). Recent studies have helped identify which colorectal lesions are at higher risk of invasive cancer and would benefit from a complete en bloc resection. Such data may guide endoscopists in making a decision on whether to use ESD or EMR for removal of large lesions. An increased number of studies have reported on the efficacy and safety of cold snare resection, even for larger polyps. These data suggest that cold snare resection may be as effective, and perhaps safer, than hot snare resection for polyps up to 1 to 2 cm in size. However, data on the threshold for cold snare resection and the value of submucosal injectates are still lacking. Use of submucosal injection is generally preferred for larger polyps, particularly those located in the proximal colon, where the colonic wall is thinner.


When Should a Patient with a Nonvariceal Upper Gastrointestinal Bleed Be Fed?
Nonvariceal upper gastrointestinal hemorrhage is a common cause for admission to the intensive care unit. Most patients are prohibited from oral or enteral feeding for 72 hours despite different risks for rebleeding. Fasting is believed to improve the ability to control intragastric pH, stabilize clots, and reduce the risk of rebleeding; however, studies have shown no difference in intragastric pH and complications in patients who received early feeding. Approximately 50% of patients are classified as low risk for rebleeding and can be safely fed immediately and discharged early, even on the same day as endoscopy. Only the patients with a high risk of rebleeding should be kept nil per os and be hospitalized for at least 72 hours after endoscopic treatment. Most high-risk lesions become low-risk lesions within 72 hours, and most rebleeding occurs within this time. Randomized controlled trials have demonstrated that early feeding does not have adverse consequences, however. More studies on the timing and type of nutrition in patients with high-risk stigmata are needed.


Influence of pregnancy after bioprosthetic valve replacement in young women: a prospective five-year study.
Prosthetic heart valve placement in young women does not normally prevent successful pregnancy, though either thrombosis in mechanical prostheses or degeneration in biological prostheses may cause risks for both mother and fetus. Although pericardial prostheses avoid the risks of anticoagulation therapy, it has been suggested that pregnancy accelerates structural degeneration in bioprostheses. The study aim was to assess the influence of pregnancy on five-year outcome after pericardial bioprosthesis replacement. A total of 85 women was studied prospectively over five years from prosthesis implantation, using annual clinical and echocardiographic investigations. Women were allocated to two groups based on pregnancy occurring during follow up: 48 patients (56%; group A) became pregnant, and 37 (44%; group B) did not. At five-year follow up, the clinical events occurred in 29 patients (34.1%): 11 (22.9%) women in group A (mean (+/-SE) linearized rate 3.6+/-0.24%/patient-year (pt-yr)), and 18 (45.6%) in group B (linearized rate 8.6+/-0.30%/pt-yr). Probability of freedom from clinical events was higher (p = 0.0096) in group A (77.9+/-6.1 versus 51.3+/-8.2%). Structural bioprosthesis degeneration, thrombosis or infective endocarditis occurred in 13 patients (27.1%) in group A (linearized rate 2.75+/-0.20%/pt-yr) and 11 (29.7%) in group B (linearized rate 2.5+/-0.18%/pt-yr). Probability of structural bioprosthesis degeneration (e.g. stenosis, calcification or rupture) did not differ (p = 0.6440) between groups (85.4+/-5.1 versus 89.5+/-5.1%), even after age-adjusted analysis (p = 0.3112). Structural changes found at five years after bioprosthesis placement may be attributed to the natural course of the bioprosthesis, and independent of any occurrence of pregnancy.


Phylogenetic analysis of major African genotype (Af2) of JC virus: Implications for origin and dispersals of modern Africans.
Both mtDNA and the Y chromosome have been used to investigate how modern humans dispersed within and out of Africa. This issue can also be studied using the JC virus (JCV) genotype, a novel marker with which to trace human migrations. Africa is mainly occupied by two genotypes of JCV, designated Af1 and Af2. Af1 is localized to central/western Africa, while Af2 is spread throughout Africa and in neighboring areas of Asia and Europe. It was recently suggested that Af1 represents the ancestral type of JCV, which agrees with the African origin of modern humans. To better understand the origin of modern Africans, we examined the phylogenetic relationships among Af2 isolates worldwide. A neighbor-joining phylogenetic tree was constructed based on the complete JCV DNA sequences of 51 Af2 isolates from Africa and neighboring areas. According to the resultant tree, Af2 isolates diverged into two major clusters, designated Af2-a and -b, with high bootstrap probabilities. Af2-a contained isolates mainly from South Africa, while Af2-b contained those from the other parts of Africa and neighboring regions of Asia and Europe. These findings suggest that Af2-carrying Africans diverged into two groups, one carrying Af2-a and the other carrying Af2-b; and that the former moved to southern Africa, while the latter dispersed throughout Africa and to neighboring regions of Asia and Europe. The present findings are discussed with reference to relevant findings in genetic and linguistic studies.


Prediction of cesarean delivery in the term nulliparous woman: results from the prospective, multicenter Genesis study.
In contemporary practice many nulliparous women require intervention during childbirth such as operative vaginal delivery or cesarean delivery (CD). Despite the knowledge that the increasing rate of CD is associated with increasing maternal age, obesity and larger infant birthweight, we lack a reliable method to predict the requirement for such potentially hazardous obstetric procedures during labor and delivery. This issue is important, as there are greater rates of morbidity and mortality associated with unplanned CD performed in labor compared with scheduled CDs. A prediction algorithm to identify women at risk of an unplanned CD could help reduced labor associated morbidity. In this primary analysis of the Genesis study, our objective was to prospectively assess the use of prenatally determined, maternal and fetal, anthropomorphic, clinical, and ultrasound features to develop a predictive tool for unplanned CD in the term nulliparous woman, before the onset of labor. The Genesis study recruited 2336 nulliparous women with a vertex presentation between 39+0 and 40+6 weeks' gestation in a prospective multicenter national study to examine predictors of CD. At recruitment, a detailed clinical evaluation and ultrasound assessment were performed. To reduce bias from knowledge of these data potentially influencing mode of delivery, women, midwives, and obstetricians were blinded to the ultrasound data. All hypothetical prenatal risk factors for unplanned CD were assessed as a composite. Multiple logistic regression analysis and mathematical modeling was used to develop a risk evaluation tool for CD in nulliparous women. Continuous predictors were standardized using z scores. From a total enrolled cohort of 2336 nulliparous participants, 491 (21%) had an unplanned CD. Five parameters were determined to be the best combined predictors of CD. These were advancing maternal age (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.09 to 1.34), shorter maternal height (OR, 1.72; 95% CI, 1.52 to 1.93), increasing body mass index (OR, 1.29; 95% CI, 1.17 to 1.43), larger fetal abdominal circumference (OR, 1.23; 95% CI, 1.1 to 1.38), and larger fetal head circumference (OR, 1.27; 95% CI, 1.14 to 1.42). A nomogram was developed to provide an individualized risk assessment to predict CD in clinical practice, with excellent calibration and discriminative ability (Kolmogorov-Smirnov, D statistic, 0.29; 95% CI, 0.28 to 0.30) with a misclassification rate of 0.21 (95% CI, 0.19 to 0.25). Five parameters (maternal age, body mass index, height, fetal abdominal circumference, and fetal head circumference) can, in combination, be used to better determine the overall risk of CD in nulliparous women at term. A risk score can be used to inform women of their individualized probability of CD. This risk tool may be useful for reassuring most women regarding their likely success at achieving an uncomplicated vaginal delivery as well as selecting those patients with such a high risk for CD that they should avoid a trial of labor. Such a risk tool has the potential to greatly improve planning hospital service needs and minimizing patient risk.


Clinical outcomes after preimplantation genetic diagnosis of patients with Corino de Andrade disease (familial amyloid polyneuropathy).
The aim of this study was to determine whether patients with transthyretin-related hereditary amyloidosis (V30M), after transplantation or under tafamidis treatment, have normal gamete reproductive capacity. A retrospective analysis was carried out of all preimplantation genetic diagnosis (PGD) cycles performed in patients with the V30M mutation. The groups analysed were: total cases with V30M, female cases with V30M and male cases with V30M. Detailed demographic, stimulation, embryological, clinical and newborn outcomes were evaluated. Comparisons revealed that patients have a high likelihood of achieving a live birth per PGD treatment cycle (48%). This is the first large report on patients with the V30M mutation treated with PGD. The high rate of live birth obtained should represent a strong stimulus for patients to use PGD as it proved to be effective and safe. As a neurodegenerative disease that leads to death, it is of maximum importance that it could be eradicated using PGD in order to definitively avoid the transmission of the disease.


Polymyxin B-mediated lysis of tumor cells.
Polymyxin B (PmB) in the concentration range of 10-50 micrograms/ml is used routinely in immunological studies to neutralize low levels of contaminating lipopolysaccharide (LPS) in media or reagents. While using PmB for such a purpose unexpected results were obtained, which led to the finding that low levels of PmB are cytotoxic to certain tumor cells. Further examination of a panel of 10 tumor cell lines revealed that in an 18-hour 51Cr release assay, EL4 cells and EL4/ADM cells were very sensitive (lysed by > or = 10 micrograms PmB/ml), C1498 cells and REH cells were moderately sensitive (lysed by > or = 20 micrograms PmB/ml) and cells of the remaining 6 lines were resistant (lysed only by 100 micrograms/ml) to PmB. A similar pattern of sensitivity was observed when 3H-thymidine incorporation was used as a measure of PmB effects in cell proliferation. The PmB concentration needed to kill 50% of the tumor cells in a suspension differed greatly among lines; thus for cells of a resistant line 8-fold more PmB was required for 50% killing than for those of a sensitive line. PmB toxicity toward EL4 cells was shown to increase to a plateau level with increasing time of exposure; however, the higher the concentration the earlier the plateau was reached. LPS may prevent PmB toxic effects since PmB binds to the lipid A portion of the LPS molecule, but 100 micrograms LPS/ml was only able to reduce the toxicity of 10 and 20 micrograms PmB/ml, and not that of 50 or 100 micrograms PmB/ml.(ABSTRACT TRUNCATED AT 250 WORDS)


[Experimental study scavenging effect of paraquat by hemoperfusion].
Objective: To determine the scavenging effect and the change of metabolism of paraquat (PQ) using hemoperfusion (HP) once and twice within 12 hours after intoxication and explore the better scheme of HP. Methods: 18 beagles were randomly divided into 3 groups. Single HP group, Double HP group and Control group. Peripheral veins blood was collected at different times within 48 hours after exposure in each group. Toxin concentration was measured, analyzed and compared among 3 groups. Results: 6 hours after exposure, Single HP group and Double HP group has finished the first HP treatment, and the concentration of PQ was lower than that of the control group, the difference was statistically significant (P<0.05) . 10 hours after exposure, there was no statistical difference of toxin concentration among 3 groups (P>0.05) . 12 hours after exposure, Double HP group has finished the second HP treatment, the concentration of PQ was significantly lower than that of Single HP group and Control group (P<0.05) . 24 hours and 48 hours after exposure, there was no statistical difference of toxin concentration among 3 groups (P>0.05) . Statistical difference were not observed in toxicokinetical parameters among 3 groups (P>0.05) . Conclusion: HP treatment once and twice within 12 hours after intoxication could effectively reduce the toxin concentration in the peripheral veins blood after HP for about 4 hours, then the toxin concentration would return to the same level as Control group quickly. It was suggested that at the beginning of poisoning, HP treatment once or twice could not significantly change the metabolism of paraquat.


Ferric Ammonium Citrate Upregulates PD-L1 Expression through Generation of Reactive Oxygen Species.
Iron plays an important role in macrophage polarization by altering metabolic and redox status. However, the impact of iron on the immune status of macrophages is still controversial. In this study, we report that ferric ammonium citrate (FAC) upregulates PD-L1 expression in macrophages. FAC not only altered the phenotype of macrophages but also led to enriching immune-modulatory T cell subsets. Since iron is known to be a constituent of coenzymes facilitating metabolic processes in mitochondria, we examined the metabolic status of FAC-overloaded macrophages by measuring the oxygen consumption rate (OCR) and the represented coenzyme, aconitase. In addition to enhancement of metabolic processes, FAC accelerated the Fenton reaction in macrophages, which also contributed to the facilitation of oxygen consumption. We reasoned that the enhancement of the OCR leads to the production of reactive oxygen species (ROS), which are directly linked to PD-L1 induction. Using ferrostatin, rotenone, and N-acetyl-L-cysteine, we confirmed that metabolic and redox regulation is responsible for FAC-mediated PD-L1 expression. Furthermore, we suggested that FAC-induced ROS production may explain FAC-mediated pro- and anti-inflammatory responses in macrophages. These findings may extend our understanding of regulating iron concentration during immune checkpoint therapy in cancer patients.


Novel Antimycobacterial Compounds Suppress NAD Biogenesis by Targeting a Unique Pocket of NaMN Adenylyltransferase.
Conventional treatments to combat the tuberculosis (TB) epidemic are falling short, thus encouraging the search for novel antitubercular drugs acting on unexplored molecular targets. Several whole-cell phenotypic screenings have delivered bioactive compounds with potent antitubercular activity. However, their cellular target and mechanism of action remain largely unknown. Further evaluation of these compounds may include their screening in search for known antitubercular drug targets hits. Here, a collection of nearly 1400 mycobactericidal compounds was screened against Mycobacterium tuberculosis NaMN adenylyltransferase ( MtNadD), a key enzyme in the biogenesis of NAD cofactor that was recently validated as a new drug target for dormant and active tuberculosis. We found three chemotypes that efficiently inhibit MtNadD in the low micromolar range in vitro. SAR and cheminformatics studies of commercially available analogues point to a series of benzimidazolium derivatives, here named N2, with bactericidal activity on different mycobacteria, including M. abscessus, multidrug-resistant M. tuberculosis, and dormant M. smegmatis. The on-target activity was supported by the increased resistance of an M. smegmatis strain overexpressing the target and by a rapid decline in NAD(H) levels. A cocrystal structure of MtNadD with N2-8 inhibitor reveals that the binding of the inhibitor induced the formation of a new quaternary structure, a dimer-of-dimers where two copies of the inhibitor occupy symmetrical positions in the dimer interface, thus paving the way for the development of a new generation of selective MtNadD bioactive inhibitors. All these results strongly suggest that pharmacological inhibition of MtNadD is an effective strategy to combat dormant and resistant Mtb strains.


Analysis of the impact of population growth in Henan Province on its environment and ecosystem.
"This paper analyzes the effects of population growth on the...environment and ecosystem [of China's Henan Province]. This paper also proposes a key countermeasure to deal with the population growth and environmental improvement of Henan Province."


Molecular genetic analysis of Drosophila eyes absent mutants reveals an eye enhancer element.
The eyes absent (eya) gene is critical for normal eye development in Drosophila and is highly conserved to vertebrates. To define regions of the gene critical for eye function, we have defined the mutations in the four viable eya alleles. Two of these mutations are eye specific and undergo transvection with other mutations in the gene. These were found to be deletion mutations that remove regulatory sequence critical for eye cell expression of the gene. Two other viable alleles cause a reduced eye phenotype and affect the function of the gene in additional tissues, such as the ocelli. These mutations were found to be insertion mutations of different transposable elements within the 5' UTR of the transcript. Detailed analysis of one of these revealed that the transposable element has become subject to regulation by eye enhancer sequences of the eya gene, disrupting normal expression of EYA in the eye. More extended analysis of the deletion region in the eye-specific alleles indicated that the deleted region defines an enhancer that activates gene expression in eye progenitor cells. This enhancer is responsive to ectopic expression of the eyeless gene. This analysis has defined a critical regulatory region required for proper eye expression of the eya gene.


Comparative haemodynamic alterations induced by pipecuronium and pancuronium.
Haemodynamic effects of pipecuronium bromide (Pi.) and pancuronium bromide (Pa.) were studied on isolated rabbit's heart, guinea pig's tracheal chain as well as the blood pressure in pentobarbital anaesthetized dogs. Pi. induced negative inotropic and chronotropic effects on the isolated rabbit's heart especially in lower concentrations. However, higher concentrations provoked two opposite effects, negative chronotropic and positive inotropic activity. In addition, Pa. in lower concentrations caused positive inotropic and negative chronotropic activity, while higher concentrations induced negative inotropic and chronotropic activity. Cardioinhibitory actions of both tested drugs are not due to either cholinergic or beta 1-adrenergic blocking effect but it may be due to nicotine-like activity. In anaesthetized dogs, i.v. injections of both tested drugs produced a transient decrease in systolic and diastolic pressure in doses above the therapeutic level. This effect may be referred to the partial ganglion blocking effect of both tested drugs.


Comparison of traps and development of a two-stage sampling plan for smokybrown cockroaches (Dictyoptera: Blattidae) outdoors.
Four commercial sticky traps were compared with jar traps for sampling smokybrown cockroaches, Periplaneta fuliginosa (Serville), outdoors. Lo-Line and Raid Roach Traps caught more cockroaches than jar traps, whereas the Mr. Sticky and Roach Motel caught < 40% of the cockroaches caught in jar traps. Sampling properties of traps (data collected over 4 yr and 3 cities) were examined retrospectively. Taylor's a and b coefficients were both significantly > 1 for jar traps, Raid Roach Trap, and Lo-Line trap. Estimating cockroach catch typical of Alabama (< 3 per trap) at single houses would require > 20 traps with a precision of 0.25 (i.e., standard error as a proportion of the mean). Taylor's power law was also used as a predictor for within-house (i.e., pooled within-house) and between-house catch variances. Coefficients for these predictors are presented that can be used in a fixed-precision 2-stage sampling plan to estimate cockroach catch from large areas.


Fibre optic surface plasmon resonance sensor system designed for smartphones.
A fibre optic surface plasmon resonance (SPR) sensor system for smartphones is reported, for the first time. The sensor was fabricated by using an easy-to-implement silver coating technique and by polishing both ends of a 400 µm optical fibre to obtain 45° end-faces. For excitation and interrogation of the SPR sensor system the flash-light and camera at the back side of the smartphone were employed, respectively. Consequently, no external electrical components are required for the operation of the sensor system developed. In a first application example a refractive index sensor was realised. The performance of the SPR sensor system was demonstrated by using different volume concentrations of glycerol solution. A sensitivity of 5.96·10(-4) refractive index units (RIU)/pixel was obtained for a refractive index (RI) range from 1.33 to 1.36. In future implementations the reported sensor system could be integrated in a cover of a smartphone or used as a low-cost, portable point-of-care diagnostic platform. Consequently it offers the potential of monitoring a large variety of environmental or point-of-care parameters in combination with smartphones.


Current Approach for Diagnosis and Treatment of Adrenal Tuberculosis-Our Experience and Review of Literature.
Addison's disease was first described by Thomas Addison in 1855. He demonstrated the destruction of bilateral adrenal gland by tuberculosis (TB) in six patients. Since then, the incidence of TB has declined in the Western world, but in developing countries, it is still the most common cause of adrenal insufficiency. Because of the introduction of antituberculous chemotherapy, the incidence of adrenal TB has been declined in the past decades. The most common symptoms are nonspecific; therefore, diagnosis is often delayed, and patients may first present with a life-threatening adrenal crisis. The most commonly identified organism for adrenal failure in adrenal TB is Mycobacterium tuberculosis infection. Adrenal TB involves bilateral adrenal glands more frequently than unilateral glands. Computed tomography (CT) scan and magnetic resonance imaging (MRI) are useful investigations to differentiate between tuberculous Addison's disease and the other causes of adrenal insufficiency. In CT scans or MRI, features of adrenal TB are bilateral adrenal enlargement and peripheral rim enhancement with or without calcifications. Antituberculous drugs, biochemical monitoring of adrenal function, and steroid therapy are essential for the management of adrenal TB and adrenal insufficiency. Here, we describe a case of adrenal TB with abscess formation followed by a review of the current literature of adrenal TB for better diagnosis and management of this condition.


Nerve-sparing Surgery for Deep Infiltrating Endometriosis: Laparoscopic Eradication of Deep Infiltrating Endometriosis with Rectal and Parametrial Resection According to the Negrar Method.
To show technical highlights of a nerve-sparing laparoscopic eradication of deep infiltrating endometriosis with rectal and parametrial resection according to the Negrar method. Stepwise demonstration of the technique with narrated video footage. Tertiary care endometriosis unit. Bowel endometriosis accounts for about 12% of the total cases of endometriosis. Most frequently, rectal infiltration also means parametrial infiltration from the widespread infiltrating disease. Its removal with inadequate anatomical surgical knowledge may lead to severe damage to visceral pelvic innervation, causing bladder, rectal, and sexual function impairments and lasting lifelong. Nerve-sparing techniques, which are the heritage of onco-gynecologic surgery, have been described to have lower post-operative bladder, rectal, and sexual dysfunctions than classical approaches. Laparoscopic excision of deep infiltrating endometriosis was performed by following the nerve-sparing Negrar technique in 6 steps: step 0-adhesiolysis, ovarian surgery, and removal of the involved peritoneal tissues; step 1-opening of pre-sacral space, development of avascular spaces, and identification and preservation of pelvic sympathetic fibers of the inferior mesenteric plexus, superior hypogastric plexus, upper hypogastric nerves, and lumbosacral sympathetic trunk and ganglia; step 2-dissection of parametrial planes, isolation of ureteral course, lateral parametrectomy, and preservation of sympathetic fibers of postero-lateral parametrium and lower mesorectum (the lower hypogastric nerves and proximal part of the inferior hypogastric plexus or pelvic plexus); step 3-posterior parametrectomy, deep uterine vein identification, and preservation of the parasympathetic pelvic splanchnic nerves and the cranial and middle part of the mixed inferior hypogastric plexus in caudad posterior parametrium and lower mesorectal planes; step 4-preserving the caudad part of the inferior hypogastric plexus in postero-lateral parametrial ligaments; step 5-preserving the caudad part of the inferior hypogastric plexus in paravaginal planes; and step 6-rectal resection and colorectal anastomosis. As shown in this case, the laparoscopic nerve-sparing complete excision of endometriosis is a feasible and reproducible technique in expert hands and, as reported in the literature, offers good results in terms of bladder morbidity reduction with higher satisfaction than the classical technique.


Recombination-dependent growth in exonuclease-depleted recBC sbcBC strains of Escherichia coli K-12.
Analysis of the aroLM-sbcCD interval of the Escherichia coli K-12 chromosome revealed a new gene (rdgC) encoding a function required for growth in recombination-deficient recBC sbcBC strains. Deletion of rdgC does not reduce viability, conjugational recombination, or DNA repair in rec+, recA, recB, recF, or recJ mutants. However, it makes the growth of recBC sbcBC strains reliant on the RecA, RecF, and RuvC proteins and, to a large extent, on RuvAB. The recBC sbcBC delta rdgC ruvAB construct forms colonies, but cell viability is reduced to < 5%. A recBC sbcBC delta rdgC derivative carrying the temperature-sensitive recA200 allele grows at 32 degrees but not 42 degrees. Multicopy rdgC+ plasmids reduce the growth rate of recBC sbcBC strains, while multicopy sbcC+ plasmids that reactivate SbcCD nuclease cannot be maintained without RdgC protein. The data presented are interpreted to suggest that exonuclease-depleted recBC sbcBC strains have difficulty removing the displaced arm of a collapsed replication fork and that this problem is compounded in the absence of RdgC. Recombination then becomes necessary to repair the fork and allow chromosome duplication to be completed. The possibility that RdgC is an exonuclease is discussed.


Not-so-supervised: A survey of semi-supervised, multi-instance, and transfer learning in medical image analysis.
Machine learning (ML) algorithms have made a tremendous impact in the field of medical imaging. While medical imaging datasets have been growing in size, a challenge for supervised ML algorithms that is frequently mentioned is the lack of annotated data. As a result, various methods that can learn with less/other types of supervision, have been proposed. We give an overview of semi-supervised, multiple instance, and transfer learning in medical imaging, both in diagnosis or segmentation tasks. We also discuss connections between these learning scenarios, and opportunities for future research. A dataset with the details of the surveyed papers is available via https://figshare.com/articles/Database_of_surveyed_literature_in_Not-so-supervised_a_survey_of_semi-supervised_multi-instance_and_transfer_learning_in_medical_image_analysis_/7479416.


Budget impact analysis of routinely using whole-genomic sequencing of six multidrug-resistant bacterial pathogens in Queensland, Australia.
To predict the cost and health effects of routine use of whole-genome sequencing (WGS) of bacterial pathogens compared with those of standard of care. Budget impact analysis was performed over the following 5 years. Data were primarily from sequencing results on clusters of multidrug-resistant organisms across 27 hospitals. Model inputs were derived from hospitalisation and sequencing data, and epidemiological and costing reports, and included multidrug resistance rates and their trends. Queensland, Australia. Hospitalised patients. WGS surveillance of six common multidrug-resistant organisms (Staphylococcus aureus, Escherichia coli, Enterococcus faecium, Klebsiella pneumoniae, Enterobacter sp and Acinetobacter baumannii) compared with standard of care or routine microbiology testing. Expected hospital costs, counts of patient infections and colonisations, and deaths from bloodstream infections. In 2021, 97 539 patients in Queensland are expected to be infected or colonised with one of six multidrug-resistant organisms with standard of care testing. WGS surveillance strategy and earlier infection control measures could avoid 36 726 infected or colonised patients and avoid 650 deaths. The total cost under standard of care was $A170.8 million in 2021. WGS surveillance costs an additional $A26.8 million but was offset by fewer costs for cleaning, nursing, personal protective equipment, shorter hospital stays and antimicrobials to produce an overall cost savings of $30.9 million in 2021. Sensitivity analyses showed cost savings remained when input values were varied at 95% confidence limits. Compared with standard of care, WGS surveillance at a state-wide level could prevent a substantial number of hospital patients infected with multidrug-resistant organisms and related deaths and save healthcare costs. Primary prevention through routine use of WGS is an investment priority for the control of serious hospital-associated infections.


Interpreting abnormal proteinuria in pregnancy: the need for a more pathophysiological approach.
This review and opinion article focuses on the definitions and meanings of abnormal protein excretion in pregnancy, asking the following questions: Are our tests to determine abnormal proteinuria adequately performed? Are current guidelines for diagnosis of excessive proteinuria, especially when used to identify preeclampsia, supported by adequate data? Can the magnitude of proteinuria be used as a reliable clinical biomarker of the gravity of preeclampsia? Should timed urine collections, primarily 24-hour excretions, be supplanted by the urine protein/creatinine ratio in clinical practice? The answers to most of these questions are: We are not sure, or some guidelines are poorly supported by data and may prove erroneous. We suggest a more physiologic approach to assessment of proteinuria and believe that if clinicians and investigators looked at proteinuria in terms of how the kidney handles protein in health and disease it would lead to a more rational and evidence-based approach to proteinuria in pregnancy. Finally, we recommend that current cutoff for abnormal proteinuria be used to diagnose preeclampsia, but the level of proteinuria should not guide management. Other variables, such as status of blood pressure control, evidence of increasing organ damage in the liver and hematological systems, evidence of falling glomerular filtration rate, and signs of neurological involvement, are more reliable indicators of severity of preeclampsia.


Wide-Range Magnetoelectric Response on Hybrid Polymer Composites Based on Filler Type and Content.
In order to obtain a wide-range magnetoelectric (ME) response on a ME nanocomposite that matches industry requirements, Tb0.3Dy0.7Fe1.92 (Terfenol-D)/CoFe₂O₄/P(VDF-TrFE) flexible films were produced by the solvent casting technique and their morphologic, piezoelectric, magnetic and magnetoelectric properties were investigated. The obtained composites revealed a high piezoelectric response (≈-18 pC·N-1) that is independent of the weight ratio between the fillers. In turn, the magnetic properties of the composites were influenced by the composite composition. It was found that the magnetization saturation values decreased with the increasing CoFe₂O₄ content (from 18.5 to 13.3 emu·g-1) while the magnetization and coercive field values increased (from 3.7 to 5.5 emu·g-1 and from 355.7 to 1225.2 Oe, respectively) with the increasing CoFe₂O₄ content. Additionally, the films showed a wide-range dual-peak ME response at room temperature with the ME coefficient increasing with the weight content of Terfenol-D, from 18.6 to 42.3 mV·cm-1·Oe-1.


Thar she blows! A novel method for DNA collection from cetacean blow.
Molecular tools are now widely used to address crucial management and conservation questions. To date, dart biopsying has been the most commonly used method for collecting genetic data from cetaceans; however, this method has some drawbacks. Dart biopsying is considered inappropriate for young animals and has recently come under scrutiny from ethical boards, conservationists, and the general public. Thus, identifying alternative genetic collection techniques for cetaceans remains a priority, especially for internationally protected species. In this study, we investigated whether blow-sampling, which involves collecting exhalations from the blowholes of cetaceans, could be developed as a new less invasive method for DNA collection. Our current methodology was developed using six bottlenose dolphins, Tursiops truncatus, housed at the National Aquarium, Baltimore (USA), from which we were able to collect both blow and blood samples. For all six individuals, we found that their mitochondrial and microsatellite DNA profile taken from blow, matched their corresponding mitochondrial and microsatellite DNA profile collected from blood. This indicates that blow-sampling is a viable alternative method for DNA collection. In this study, we show that blow-sampling provides a viable and less invasive method for collection of genetic data, even for small cetaceans. In contrast to dart biopsying, the advantage of this method is that it capitalizes on the natural breathing behaviour of dolphins and can be applied to even very young dolphins. Both biopsy and blow-sampling require close proximity of the boat, but blow-sampling can be achieved when dolphins voluntarily bow-ride and involves no harmful contact.


A Single Nanoprobe for Ratiometric Imaging and Biosensing of Hypochlorite and Glutathione in Live Cells Using Surface-Enhanced Raman Scattering.
Hypochlorite (ClO-) and glutathione (GSH) have been reported to closely correlate with oxidative stress and related diseases; however, a clear mechanism is still unknown, mainly owing to a lack of accurate analytical methods for live cells. Herein we create a novel surface-enhanced Raman scattering (SERS) nanoprobe, 4-mercaptophenol (4-MP)-functionalized gold flowers (AuF/MP), for imaging and biosensing of ClO- and GSH in RAW 264.7 macrophage cells upon oxidative stress. The SERS spectra of AuF/MP change with the reaction between ClO- and 4-MP on AuFs within 1 min and then recover after reaction with GSH, resulting in the ratiometric detection of ClO- and GSH with high accuracy. The single SERS probe also shows high selectivity for ClO- and GSH detection against other reactive oxygen species and amino acids which may exist in biological systems, as well as remarkable sensitivity ascribed to a larger amount of hot spots on AuFs. The significant analytical performance of the developed nanoprobe, together with good biocompatibility and high cell-permeability, enables the present SERS probe imaging and real-time detection of ClO- and GSH in live cells upon oxidative stress.


A comparison of clinical evaluation tools in hospitals and baccalaureate nursing programs.
This study compared nurse educators' and hospital administrators' expectations of graduating baccalaureate students by analyzing the content of clinical evaluation tools in two settings: the last medical-surgical rotation and the beginning staff-level position. Ten baccalaureate nursing programs and 10 large university hospitals were studied as pairs. Evaluation tool criteria were divided into six role categories: care giver, client teacher, manager-team member, communicator, investigator, and professional. The study yielded data regarding similarities and differences regarding behaviors expected by schools and hospitals. The highest rates of similarity were found in the care giver and professional roles. The greatest difference was found in the manager-team member role with hospitals including many more of the behaviors. Few behaviors in the investigator role were included by school-hospital pairs, but schools included more of the behaviors than hospitals.


A cohort study of mortality predictors in patients with acute exacerbation of chronic fibrosing interstitial pneumonia.
To assess clinical, laboratory and radiographic findings associated with outcomes and to clarify more practical ways to predict hospital mortality in patients with acute exacerbation (AE) of chronic fibrosing interstitial pneumonia (CFIP). Single-centre retrospective cohort study. University Hospital in Japan. We identified 51 consecutive patients with AE of idiopathic CFIP through multidisciplinary discussion. Patients who had connective tissue disease, drug-induced lung disease, pneumoconiosis, hypersensitivity pneumonitis, sarcoidosis, pulmonary histiocytosis, lymphangioleiomyomatosis and eosinophilic pneumonia were excluded. There were no interventions. The main outcome was determination of in-hospital mortality predictors. Other outcomes included clinical, laboratory and radiographic differences between non-survivors and survivors in patients with AE of CFIP. The mean age of the patients with AE of CFIP was 71 years. Compared with survivors, non-survivors had a significantly shorter duration of symptoms before admission, lower prevalence of peripheral distribution of ground-glass opacity and centrilobular emphysema (CLE) on thin-section CT, lower peripheral lymphocyte count, higher brain natriuretic peptide titre, lower Pao2:Fio2 (P:F) ratio, higher prevalence of systemic inflammatory response syndrome (SIRS) and higher SIRS score on admission (p=0.0069, 0.0032, 0.015, 0.040, 0.0098, 0.012, 9.9×10(-7) and 5.4×10(-6), respectively). Multivariate analysis revealed SIRS (HR=6.2810, p=0.015), CLE (HR=0.0606, p=3.6×10(-5)) and serum procalcitonin level (HR=2.7110, p=0.022) to be independent predictors of in-hospital mortality. A Kaplan-Meier estimate on the basis of stratification according to the presence or absence of SIRS and CLE demonstrated a distinct survival curve for each subset of patients. Distinct survival curves documented by stratification according to the presence or absence of SIRS and CLE may provide basic information for a rational management strategy for patients with AE of CFIP on admission.


Restoration of self-sustained circadian rhythmicity by the mutant clock allele in mice in constant illumination.
Mice mutant for the Clock gene display abnormal circadian behavior characterized by long circadian periods and a tendency to become rapidly arrhythmic in constant darkness (DD). To investigate whether this result is contingent on the absence of light, the authors studied the circadian behavior of homozygous Clock mutant mice under conditions of both constant light and DD. Fourteen of 15 Clock/Clock mice stayed rhythmic in constant light of 70 to 170 lux, where 10 of 15 wild-type mice became arrhythmic. In contrast, only 5 of 15 Clock/ Clock mice and 15 of 15 wild-type mice remained rhythmic after 60 cycles when released in DD (dim red light of < 1.5 lux) after 8 days of entrainment. The restoration of self-sustained rhythmicity by the Clock allele cannot be attributed to reduced sensitivity of the system to light It underscores the fact that self-sustainment is not a secure guide to functional organization.


Proposed terms and concepts for describing and evaluating animal-health surveillance systems.
The information provided by animal-health surveillance helps to reduce the impact of animal diseases. The widespread movement of animals and their products around the world results in an increasing risk that disease will spread. There is, therefore, a need for exchange between countries of comparable information about disease incidence; the exchange must be based on a common understanding of surveillance approaches and how surveillance systems are designed and implemented. Establishing agreed-upon definitions of surveillance terms would be a first step in achieving this standardisation, and will enhance transparency and confidence. To this end, a workshop was held with the aim of agreeing upon key terms and concepts for animal-health surveillance. In this paper, we describe the methods used at the workshop and summarise the discussions. A complete list of all the proposed definitions including lists of characteristics that can be used to describe surveillance activities and attributes for evaluation of surveillance is available in the workshop report (available at http://www.defra.gov.uk/ahvla-en/disease-control/surveillance/icahs-workshop/). Some important issues were highlighted during these discussions; of particular note was the importance of economic efficiency as an evaluation attribute. Some remaining inconsistencies in the proposed use of terms are highlighted (including the definition of 'risk-based surveillance' and the use of the term 'event-based surveillance').


Q-switched nd(3+) glass laser of variable temporal coherence.
This paper describes a single transverse mode Q-switched Nd(3+) glass laser working on a few longitudinal adjacent modes. The narrowing of the spectral output is obtained by use of a resonant reflector and a birefringent filter under temperature control. The number of longitudinal modes is varied from one to ten with a constant energy output of 10 mJ by means of intracavity resonators and two-step Q-switching. Observations of the quasiperiodic intensity fluctuations during the 40-nsec pulse give information about the statistical character of multimode giant pulse laser emission.


Immunohistochemical detection and correlation between MHC antigen and cell-mediated immune system in recurrent glioma by APAAP method.
As part of an on-going clinical trial of immunotherapy for recurrent malignant gliomas, using alkaline phosphatase-anti-alkaline phosphatase method with monoclonal antibodies, we investigated the correlation between expression of the major histocompatibility complex (MHC) and the subpopulation of tumor-infiltrating lymphocytes (TILs) in 38 glioma specimens (20 grade IV, 11 grade III, and 7 grade II) from 33 patients. Thirty specimens (78.9%) were positive to class I MHC antigen and 20 (52.6%) were positive to class II MHC antigen. The correlations between class I MHC antigen expression and the number of infiltrating T8 (p less than 0.01), and also between class II MHC antigen expression and the number of infiltrating T4 (p less than 0.05) were significant. We conclude that TILs are the result of immunoreaction (host-defense mechanism). 31.6% of specimens had perivascular infiltration of T cells. The main infiltrating lymphocyte subset in moderate to marked perivascular cuffing was T4. Our results may indicate that lack of MHC antigen on the glioma cell surface has a share in the poor immunogenicity in glioma-bearing patients. In addition, considering the effector/target ratio, the number of infiltrating lymphocytes against glioma cells was too small, so the immunological intervention seems to be essential in glioma therapy. Previous radiation therapy and chemotherapy, including steroid therapy, did not influence lymphocyte and macrophage infiltration.


[The role and limitations of FDG-PET in head and neck cancer].
18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a nuclear medicine imaging technique which has been increasingly applied as a diagnostic tool. The usefulness of FDG-PET may be described as follows: I . Early detection of cancer; II. Diagnosis of cancer; III. Detection of nodal or distant metastasis, and double cancer; IV. Detection of unknown primary tumor with metastatic neck lesions; and V. Evaluation of treatment of head and neck cancer. FDG-PET is especially useful to detect distant metastasis, double cancer with head and neck cancer and unknown primary tumor with metastatic neck lymph nodes. The conventional modalities, e. g., CT or MRI, show anatomical images in the body. On the other hand, FDG-PET reveals three-dimensional images of functional processes of the glucose metabolism. FDG-PET can estimate metabolic activity in cancer and is useful in evaluating or monitoring the response to concurrent chemoradiotherapy of the head and neck cancer. However, we should recognize the limitations of FDG -PET. An acute inflammatory disease shows high FDG uptake like cancer. It is difficult to detect early-stage esophageal cancer or to diagnose parotid gland cancer.


Characteristics of ATP-induced current through P2X7 receptor in NG108-15 cells: unique antagonist sensitivity and lack of pore formation.
ATP activates the mouse P2X7 receptor and induces a nonselective-cation current in NG108-15 cells. We investigated the effects of five receptor antagonists on the ATP-induced nonselective-cation current through P2X7 receptor (I(NS.P2X7)) in NG108-15 cells. Nonselective P2 receptor antagonists, RB-2, PPADS and suramin inhibited the I(NS.P2X7) with IC50 values of 4.3, 53 and 40 microM, respectively. However, KN-04, which is a potent antagonist of human P2X7 receptors but is not that of rat P2X7 receptors, had only a weak blocking effect. Furthermore, oxidized-ATP (300 microM), an antagonist of the P2X7 receptor-mediated pore-formation, did not affect the I(NS.P2X7). Prolonged ATP application did not increase the membrane permeability to large molecules, N-methyl-D-glucamine or Yo-Pro-1, indicating that pore-formation was not promoted by the P2X7 receptor activation in NG108-15 cells. These results suggest that antagonist sensitivities and pore-forming properties of the P2X7 receptors in NG108-15 cells are different from those of other cells types.


Mechanism of syncope in patients with heart disease and negative electrophysiologic test.
In patients with syncope and structural heart disease, syncope is suspected to be attributable to a primary cardiac arrhythmia, but little is known of its mechanism when electrophysiologic study is unremarkable. We applied an implantable loop recorder in 35 patients with overt heart disease at risk of ventricular arrhythmia, because these were patients with previous myocardial infarction or cardiomyopathy with depressed ejection fraction or nonsustained ventricular tachycardia in whom an electrophysiologic study was unremarkable. During a follow-up of 3 to 15 months, syncope recurred in 6 patients (17%) after a mean of 6+/-5 months; in 3 patients, the mechanism of syncope was bradycardia with long pauses (sudden-onset AV block in 2 cases and sinus arrest in 1 case); in 1 patient, there was stable sinus tachycardia; and in 2 patients, who had chronic atrial fibrillation, there was an increase in ventricular rate. A total of 23 episodes of presyncope were documented in 8 patients (23%): no rhythm variation or mild tachycardia in 12 cases, paroxysmal atrial fibrillation or atrial tachycardia in 10 cases, and sustained ventricular tachycardia in 1 case. No patient died during the study period nor suffered from injury attributable to syncopal relapse. The patients with unexplained syncope, structural heart disease, and negative electrophysiologic study had a favorable medium-term outcome with no case of death and a low recurrence rate of syncope without related injury. The mechanism of syncope was heterogeneous, and ventricular tachyarrhythmia was unlikely.


[Hypertension in the elderly: definition, indications for treatment and clarification].
Hypertension is the single most potent common and remediable risk factor for cardiovascular morbidity and mortality in the population over age 65. Data from newer intervention studies show that it is clearly beneficial to treat elderly patients with either both systolic and diastolic hypertension or with isolated systolic hypertension. The indication to start treatment in a given patient depends on blood pressure values, age and eventual concomitant disease. In the evaluation of the elderly hypertensive patient, multiple blood pressure measurements in the standing and lying patient should be taken. In the case of suspected carotid artery stenosis, a Doppler ultrasound is indicated before starting antihypertensive therapy. Finally, if refractory hypertension or kidney failure develop in an elderly patient, renal artery stenosis should be considered.


Spatial wavelet analysis of calcium oscillations in developing neurons.
Calcium signals play a major role in the control of all key stages of neuronal development, and in particular in the growth and orientation of neuritic processes. These signals are characterized by high spatial compartmentalization, a property which has a strong relevance in the different roles of specific neuronal regions in information coding. In this context it is therefore important to understand the structural and functional basis of this spatial compartmentalization, and in particular whether the behavior at each compartment is merely a consequence of its specific geometry or the result of the spatial segregation of specific calcium influx/efflux mechanisms. Here we have developed a novel approach to separate geometrical from functional differences, regardless on the assumptions on the actual mechanisms involved in the generation of calcium signals. First, spatial indices are derived with a wavelet-theoretic approach which define a measure of the oscillations of cytosolic calcium concentration in specific regions of interests (ROIs) along a cell, in our case developing chick ciliary ganglion neurons. The resulting spatial profile demonstrates clearly that different ROIs along the neuron are characterized by specific patterns of calcium oscillations. Next we have investigated whether this inhomogeneity is due just to geometrical factors, namely the surface to volume ratio in the different subcompartments (e.g. soma vs. growth cone) or it depends on their specific biophysical properties. To this aim correlation functions are computed between the activity indices and the surface/volume ratio along the cell: the data thus obtained are validated by a statistical analysis on a dataset of [Formula: see text] different cells. This analysis shows that whereas in the soma calcium dynamics is highly correlated to the surface/volume ratio, correlations drop in the growth cone-neurite region, suggesting that in this latter case the key factor is the expression of specific mechanisms controlling calcium influx/efflux.


[miR-125b regulates osteogenic differentiation of human bone marrow mesenchymal stem cells by targeting Smad4].
To investigate whether miR-125b regulates the osteogenic differentiation of bone marrow mesenchymal stem cells (MSCs) by modulating Smad4, a predicted target in silicon. Smad4 3'-UTR-luciferase vector was constructed and dual-luciferase reporter gene assay was employed to examine the effect of miR-125b on luciferase activity. MSCs were isolated and cultured from human bone marrow, and then transfected with miR-125b mimics followed by induction of osteogenic differentiation. qRT-PCR and Western blot were used to detect the expressions of Smad4 mRNA and protein. MSCs were induced into the osteoblasts after transfecting with Smad4 siRNA, and the effect of Smad4 downregulation on osteogenic differentiation was observed by AKP activity and RUNX2 mRNA levels. miR-216b bound Smad4 3'-UTR and inhibited the luciferase activity (P<0.05). Smad4 mRNA and protein expressions were significantly down-regulated in the MSCs induced into osteogenic differentiation when miR-125b was overexpressed. Downregulation of Smad4 suppressed the AKP activity and RUNX2 mRNA expression, indicating that Smad4 siRNA simulated at least in part the function of miR-125b as the regulator of MSCs osteogenic differentiation. miR-125b can suppress MSCs osteogenic differentiation by directly targeting Smad4.


A 3D view on free-floating, space-fixed and surface-bound para-phenylene nanofibres.
Nanofibres from para-hexaphenylene and functionalized quaterphenylene molecules are grown on mica surfaces and are thereafter transferred into solution, where they either freely rotate in water or are space-fixed in sucrose. From freely rotating aggregates highly anisotropic angular intensity distributions of emitted light for individual aggregates are determined. Luminescence is enhanced at the nanofibre tip as compared to the broad side by about an order of magnitude probably due to waveguiding along the long axis of the aggregates. For dense arrays of nanofibres on mica the increase of emitted intensity towards the substrate plane in the direction of the long axes of the nanofibres is smaller and it depends on the effective thickness of the nanofibre films. The difference between individual aggregates and aggregate arrays is interpreted in terms of light scattering at surface roughness inside the nanofibre film and on the border of the underlying mica substrate. Aggregates fixed in solution, with the help of femtosecond laser scanning microscopy, allow us to obtain two-photon absorption spectra of functionalized nanofibres between 720 and 900 nm as well as morphological features from three-dimensional optical images. The lateral resolution is about 400 nm.


A Swelling-Activated Chloride Current in Microglial Cells is Suppressed by Epac and Facilitated by PKA - Impact on Phagocytosis.
Volume-regulated anion channels (VRACs) are of particular importance in regulating the cell volume (CV) and give rise to the swelling-activated Cl- current (ICl,swell), a main component driving global regulatory volume decrease (RVD) during cell swelling. Because ICl,swell affects numerous CV-regulated processes like migration, we assume that its role is also indispensable for phagocytosis which requires local cell swelling. Noradrenaline (NA) modulates phagocytosis in macrophages and microglial cells, macrophage-related cells in the central nervous system. Therefore we evaluated whether NA modulates ICl,swell and phagocytosis in microglia. Experiments were performed in murine microglial BV-2 and primary mouse microglial cells. Patch clamp experiments were performed in BV-2 cells using the amphotericin-perforated method to minimize cytosolic disturbances. Phagocytosis was quantified by scanning electron microscopy. Following activation of ICl,swell by a hypotonic bath solution, noradrenaline, as well as the β-adrenergic agonist isoproterenol, evoked a transient decrease of ICl,swell. Repeated application of adrenergic agonists caused a decline of this electrical response. Application of the agonist of exchange protein directly activated by cAMP (Epac), 8-pCPT-2-O-Me-cAMP, or the protein kinase A inhibitor H89 caused a persistent suppression of ICl,swell. When isoproterenol was added concomitantly with the hypotonic saline, ICl,swell developed more rapidly compared to control conditions. Uptake of IgG-coated beads was suppressed by NA or H89 when quantified after 15 min of exposure. The activation of β-adrenergic receptors in microglial cells triggers a cAMP-Epac-dependent and a cAMP-PKA-dependent cascade which affects phagocytosis via modulation of the swelling-activated Cl- current ICl,swell.


Pharmacists' attitudes toward PAs. Results of a Wisconsin study.
Eight months after physician assistants in Wisconsin were given the authority to write prescriptions, a survey of pharmacists in that state indicated that PAs were utilizing the privilege. The survey further concluded that the technical quality of prescriptions written by PAs was appropriate, that pharmacists have confidence in prescription writing by PAs, and that other professionals in health care and the public need to be informed about PA prescribing authority.


Current trends in the treatment of upper gastrointestinal disease.
The past 25 years have seen an amazing improvement in the treatment and understanding of acid-related disorders. In particular, the introduction of selective histamine receptor antagonists and proton pump inhibitors has made the medical control of acid secretion an effective means of therapy. The demonstration that infection with Helicobacter pylori is responsible for most cases of peptic ulcer disease resulted in another major improvement in therapy in these areas as a result of the eradication of the organism. Research continues in an attempt to find improved means of acid control and better methods for the eradication of H. pylori based on unique proteins expressed by the organism to resist gastric acidity.


Propantheline prevention of mucositis from etoposide.
Mucosal toxicity is dose limiting for etoposide. This may be related to the direct effects of etoposide on the mucosa. Twelve patients receiving etoposide 1800 mg/m2 as part of a myeloablative pre-transplant regimen were randomized to receive propantheline 30 mg or placebo orally every 6 h for six doses. Mucositis was less frequent (2 of 6 vs 5 of 6) and less severe (p = 0.05) in the propantheline arm. There were no differences in tumor response or survival between the two groups. Propantheline is an anticholinergic that causes xerostomia by decreasing salivation. Propantheline may reduce the salivary excretion of etoposide and could reduce its toxic effects on the mucosa. Propantheline is effective in reducing the incidence and severity of mucositis in patients receiving high-dose etoposide.


Identification of secreted and membrane proteins in the rat incisor enamel organ using a signal-trap screening approach.
The secretome represents the subset of proteins that are targeted by signal peptides to the endoplasmic reticulum. Among those, secreted proteins play a pivotal role because they regulate determinant cell activities such as differentiation and intercellular communication. In calcified tissues, they also represent key players in extracellular mineralization. This study was carried out to establish a secretome profile of rat enamel organ (EO) cells. A functional genomic technology, based on the signal trap methodology, was applied, starting with a library of 5'-enriched cDNA fragments prepared from rat incisor EOs. A total of 2,592 clones were analyzed by means of macroarray hybridizations and DNA sequencing. Ninety-four unique clones encoding a signal peptide were retrieved. Among those were 84 matched known genes, many not previously reported to be expressed by the EO. Most importantly, 10 clones were classified as being novel, with EO-009 identified as the rat homolog of human APin protein. These data indicate that many secreted and membrane-embedded EO proteins still remain to be identified, some of which may play crucial roles in regulating processes that create an optimal environment for the formation and organization of apatite crystals into a complex three-dimensional calcified matrix.


RNA recovery from specimens of duct-washing cytology performed contemporaneously with mammary ductoscopy.
Conventional cytological diagnosis including duct-washing cytology (DWC) is sometimes performed using ductal epithelial cells collected during mammary ductoscopy; it is useful for detection of early-stage breast cancer such as ductal carcinoma in situ (DCIS). However, conventional cytological diagnosis focuses exclusively on cellular morphology; false negatives and false positives may be caused by inadequate specimen preparation (triggering cell degeneration) or poor examiner diagnostic skills. Molecular diagnosis using RNA biomarkers is expected to compensate for the weaknesses of cytological diagnosis. We previously employed microarray analysis to identify highly expressed genes in DCIS, suggesting that they may be useful for DCIS diagnosis. Here, we explored whether DWC samples yielded RNA of sufficient quantity and quality for RNA biomarker-based diagnosis. We extracted RNAs from 37 DWC samples. RNA from 12 samples exhibited RNA integrities of ≥ 6, indicative of moderate-to-high quality. We then showed that cocaine and amphetamine regulated transcript prepropeptide (CARTPT) and breast cancer-associated transcript 54 (BRCAT54) mRNA-previously shown by microarray analysis to be highly expressed in DCIS-were detectable in these samples. Therefore, DWC samples may be useful for molecular diagnosis involving RNA biomarkers.


Public Health Benefits from Livestock Rift Valley Fever Control: A Simulation of Two Epidemics in Kenya.
In controlling Rift Valley fever, public health sector optimises health benefits by considering cost-effective control options. We modelled cost-effectiveness of livestock RVF control from a public health perspective in Kenya. Analysis was limited to pastoral and agro-pastoral system high-risk areas, for a 10-year period incorporating two epidemics: 2006/2007 and a hypothetical one in 2014/2015. Four integrated strategies (baseline and alternatives), combined from three vaccination and two surveillance options, were compared. Baseline strategy included annual vaccination of 1.2-11% animals plus passive surveillance and monitoring of nine sentinel herds. Compared to the baseline, two alternatives assumed improved vaccination coverage. A herd dynamic RVF animal simulation model produced number of animals infected under each strategy. A second mathematical model implemented in R estimated number people who would be infected by the infected animals. The 2006/2007 RVF epidemic resulted in 3974 undiscounted, unweighted disability adjusted life years (DALYs). Improving vaccination coverage to 41-51% (2012) and 27-33% (2014) 3 years before the hypothetical 2014/2015 outbreak can avert close to 1200 DALYs. Improved vaccinations showed cost-effectiveness (CE) values of US$ 43-53 per DALY averted. The baseline practice is not cost-effective to the public health sector.


Lower transfer factor of the lung for carbon monoxide in women with a patent foramen ovale.
What is the central question of this study? Do individuals with a patent foramen ovale (PFO+ ) have a lower lung transfer factor for carbon monoxide than those without (PFO- )? What is the main finding and its importance? We found a lower rate constant for carbon monoxide uptake in PFO+ compared with PFO- women, which was physiologically relevant (≥0.5 z-score difference), but not for PFO+ versus PFO- men. This suggests that factors independent of the PFO are responsible for our findings, possibly inherent structural differences in the lung. The transfer factor of the lung for carbon monoxide (TLCO ) measure assumes that all cardiac output flows through the pulmonary circuit. However, right-to-left blood flow through a shunt can result in a lower transfer factor than predicted. A patent foramen ovale (PFO) is a potential source of right-to-left shunt that is present in ∼35% of the population, but the effect of PFO on TLCO is unknown. We sought to determine the effect of PFO on the TLCO . We conducted a retrospective analysis of TLCO data from 239 (101 women) participants. Anthropometrics and lung function, including spirometry, plethysmography and TLCO , were compiled from our previously published work. Women, but not men, with a PFO had a significantly lower TLCO and rate constant for carbon monoxide uptake (KCO ) (percentage of predicted and z-score) than women without a PFO. Women and men with a PFO had normal alveolar volumes that did not differ from those without a PFO. Correcting the data for haemoglobin in a subset of subjects did not change the results (n = 58; 25 women). The lower KCO in women with versus without a PFO was physiologically relevant (≥0.5 z-score difference). There was no effect of PFO in men. This suggests that factors independent of the PFO are responsible for our findings, possibly inherent structural differences in the lung.


Imaging of the complications of laparoscopic cholecystectomy.
Laparoscopic cholecystectomy has, in recent years, emerged as the gold standard therapeutic option for the management of uncomplicated symptomatic cholelithiasis. Each year, up to 700,000 of these procedures are performed in the United States alone. While the relative rate of post-procedural complications is low, the popularity of this method of gallbladder removal is such that this entity is not uncommonly clinically encountered, and therefore must be borne in mind by the investigating physician. By way of pictorial review, we explore the radiological appearances of a variety of potential complications of laparoscopic cholecystectomy. The radiological appearances of each shall be illustrated in turn using several imaging modalities, including ultrasound, computed tomography, MR cholangiography and radio-isotope scintigraphy. From calculus retention to portal vein laceration, bile duct injury to infected dropped calculi, we illustrate numerous potential complications of this procedure, as well as indicating the most suitable imaging modalities available for the detection of these adverse outcomes. As one of the most commonly performed intra-abdominal surgeries, laparoscopic cholecystectomy and the complications thereof are not uncommonly encountered. Awareness of the possible presence of these numerous complications, including their radiological appearances, makes early detection more likely, with resultant improved patient outcome.


Weed control in rose-scented geranium (Pelargonium spp).
Abstract: Field investigations were carried out during 1999 and 2000 to identify effective chemical/ cultural methods of weed control in rose-scented geranium (Pelargonium spp). The treatments comprised pre-emergence applications of oxyfluorfen (0.15, 0.20 and 0.25 kg AI ha(-1)) and pendimethalin (0.50, 0.75 and 1.00kg AI ha(-1)), successive hand weeding, hoeing and mulching using spent of lemon grass (at 5 tonnes ha(-1)) 45 days after planting (DAP), three hand-weedings 30, 60 and 90 DAP, weed-free (frequent manual weeding) and weedy control. Broad-leaf weeds were more predominant than grass and sedge weeds, accounting for 85.8% weed density and 93.0% weed dry weight in 1999 and 77.2% weed density and 93.9% weed dry weight in 2000. Unrestricted weed growth significantly reduced geranium oil yield, by 61.6% and 70.6% in 1999 and 2000, respectively. Pre-emergence application of pendimethalin (0.75-1.00 kgAI ha(-1)) or oxyfluorfen (0.25 kg AI ha(-1)), successive hand-weeding, hoeing and mulching and three hand-weedings were highly effective in reducing weed density and dry weight and gave oil yield comparable to the weed-free check. Application of oxyfluorfen (0.15 or 0.20 kg AI ha(-1)) and pendimethalin (0.50 kg AI ha(-1)) were less effective in controlling the weed species in geranium. None of the herbicides impaired the quality of rose-scented geranium oil measured in terms of citronellol and geraniol content.


In-depth TEM characterization of block copolymer pattern transfer at germanium surfaces.
Dry plasma etching for the pattern transfer of mask features is fundamental to semiconductor processing and the development of device and electrically conducting elements becomes more challenging as features reach the deep nanoscale regime. In this work, high resolution transmission electron microscopy (TEM) coupled with energy dispersive x-ray (EDX) characterization were used to analyze the pattern transfer of graphoepitaxially aligned block copolymer (BCP) features to germanium (Ge) substrates as a function of time. The BCP patterns were converted into metal oxide hardmasks in order to affect good aspect ratios of the transferred features. An unusual interface layer between metal oxide nanowires and the germanium-on-insulator substrate was observed. EDX analysis shows that the origin of this interface layer is a result of the presence of a negative tone e-beam resist material, HSQ (hydrogen silsesquioxane). HSQ was employed as a guiding material to align line-space features of poly(styrene)-block-poly(4-vinylpyridine) (PS-b-P4VP) BCP with 16 nm half-pitch topography. Additionally, the existence of a metal oxide layer (from the initial PS-b-P4VP film) is also shown through ex situ TEM and EDX characterization. Three dimensional modeling of features is also provided giving a unique insight into the arrangement and structure of BCP features prior to and after the pattern transfer process. The results presented in this article highlight the accuracy of high resolution electron microscopy and elemental mapping of BCP generated on-chip etch masks to observe and understand through-film features affecting pattern transfer.


Role of ITAM-containing adapter proteins and their receptors in the immune system and bone.
The immunoreceptor tyrosine-based activation motif (ITAM) is a highly conserved region in the cytoplasmic domain of signaling chains and receptors and is a critical mediator of intracellular signals. ITAM-mediated signals depend on the Syk or zeta-associated protein of 70 kDa tyrosine kinases, and ITAM signaling is required for the differentiation and function of B and T cells in adaptive immunity. ITAM-dependent receptors also regulate the function of innate immune cells, including natural killer cells, and myeloid-derived cells such as macrophages, neutrophils, dendritic cells, and mast cells. Myeloid lineage cells also include osteoclasts (OCLs), the cells required for bone resorption, and recent studies show a critical role for the ITAM-containing adapter proteins DAP12 and the FcRgamma chain (Fcepsilon receptor I gamma chain) in OCL differentiation. Mice deficient in both the DAP12 and FcRgamma ITAM-bearing adapters are significantly osteopetrotic with a severe defect in OCL differentiation, demonstrating the requirement for ITAM signals in bone and further implicating this pathway in the development of highly specialized cell functions in hematopoietic cells. Regulation of osteoclastogenesis by ITAM-dependent receptors suggests that OCLs, similar to related myeloid cells, are tightly controlled by arrays of receptors that allow them to sense and respond to their local microenvironment like other innate immune cells.


Doping-Dependent Optical Response of a Hybrid Transparent Conductive Oxide/Plasmonic Medium.
Understanding the interaction between plasmonic nanoparticles and transparent conductive oxides is instrumental to the development of next-generation photovoltaic, optoelectronic, and energy-efficient solid-state lighting devices. We investigated the optical response of hybrid media composed of gold nanoparticles deposited on aluminum-doped zinc oxide thin films with varying doping concentration by spectroscopic ellipsometry. The dielectric functions of bare AZO were addressed first, revealing doping-induced effects such as the band gap shift and the appearance of free carriers. In the hybrid media, a blue-shift of the localized surface plasmon resonance of Au NPs as a function of increasing Al doping of the substrate was observed, ascribed to the occurrence of a charge transfer between the two materials and the doping-dependent variation of the polarizability of the substrate.


[Subacute myopathy revealing hyperthyroidism].
Progressively increasing muscle weakness of the proximal regions of the lower limbs over a period of two months in a 57-year-old woman was found to be due to an undiagnosed hyperthyroidism. Total relief from muscle weakness was obtained when euthyroidism was restored. In spite of its rarity, hyperthyroidal myopathy should be suspected in all cases of acquired myopathic disorders in adults inasmuch treatment of the hyperthyroidism leads to recovery.


Introduction to resources in molecular genetics.
Perhaps no other discipline has experienced as dramatic an information explosion in recent years as has the field of molecular genetics. While the flood of scholarly publications stemming from this research has been extensively indexed in MEDLINE, a number of new databases have been developed that provide direct access to the primary sequence data as well as to curated, reference information. A select group of these databases, including NCBI's GenBank, LocusLink, RefSeq, OMIM, and Genes and Disease, is examined. Following a brief description of each database, a proposed instructional program for their integration into an undergraduate genetics course at the University of Vermont is described.


Advanced breast cancer with cachexia: A case report.
Cachexia is a clinically relevant syndrome in cancer that is associated with reduced tolerance to anticancer therapy, reduced quality of life, and reduced survival rates. Cachexia is most prevalent in pancreatic, gastric, colorectal, lung, and head and neck cancers. It is rarely documented in breast cancer patients. In our case report of a breast cancer patient with bone metastasis who was monitored throughout the course of her treatment, we document the development of cachexia using image analyses in relation to her metastatic burden. In the 2-year period, from April 10, 2015, to February 09, 2017, she lost 16% of her baseline weight. During this time, she was repeatedly hospitalized for chest tightness, edema of both lower limbs, numbness and pain in the left lower extremity and backache. Our patient was a 46-year-old premenopausal woman when she was firstly diagnosed. Several years after surgery for invasive ductal carcinoma of the left breast, she had multiple systemic bone metastases (the thoracic spine, the ribs, etc), lung metastasis, bilateral axillary lymph node metastasis, and metastasis of the right neck lymph node in IV area. The patient completed 6 cycles of postoperative adjuvant chemotherapy and long-term endocrine therapy after a radical mastectomy for breast cancer. During the fourth progression, 6 cycles of rescue chemotherapy were performed. Local lumbosacral radiotherapy, and lumbar surgery were carried out to relieve symptoms after several progressions. She became extremely thin, weighing only 50 kg at admission on July 23, 2018. This eventually led to multiple organ failure and death. We noted a strong negative correlation between the abdominal muscle area and the metastatic tumor area at the second lumbar vertebral (L2) level. The monitoring of abdominal muscle wasting may serve as a marker, and therefore a prognostic factor, for both cachexia and the extent of metastatic disease. This is especially true with breast cancer, where metastasis to bone is frequent. Our data from a computational tomography radiological quantification, may provide clinicians with early indications of the extent of cachexia in metastatic breast cancer patients.


Effect of a 1 year combined aerobic- and weight-training exercise programme on aerobic capacity and ventilatory threshold in patients suffering from coronary artery disease.
Weight-training is recommended as a complement to conventional aerobic-training for most low to moderate risk patients suffering from coronary artery disease (CAD). The purpose of this study was to evaluate the effect of a 1 year exercise programme combining weight- and aerobic-training on peak oxygen uptake (V*O2,peak) and ventilatory threshold (VT). We studied 40 men suffering CAD who were divided into three groups: 14 subjects to weight-training plus aerobic-training [mean (SD] [combined exercise group, age 55 (10) years], 14 to aerobic-training only [aerobic-training group, age 57 (11) years], and 12 to a control group [standard care, age 57 (11) years]. A symptom-limited graded exercise test using the standard Bruce protocol was performed using a 12-lead electrocardiogram, and gas analysis techniques. Muscle strength was determined only in the combined exercise group using the one-repetition maximum method on each of eight weight exercises. Arm and leg strength increased by 21.9% and 27.8% respectively ( P<0.0001) from pre to post-tests. The V*O2,peak did not differ between the combined and aerobic-training groups but their adjusted means were greater than those of the control group [39 (1.8) and 35.3 (1.8) compared to 26.2 (2.7) ml.kg(-1).min(-1) ( P<0.001)]. The oxygen uptake at VT was higher in the combined group [24.7 (1.4) ml.kg(-1).min(-1)] compared to aerobic [18.7 (1.4) ml.kg(-1).min(-1)] and control [13.6 (1.7) ml.kg(-1)min(-1)] groups ( P<0.001). Similar results were found for exercise tolerance (treadmill time to peak and at VT). Combined exercise training increased the VT more than aerobic-training alone. Combined exercise training did not improve the V*O2,peak or the functional capacity more than aerobic-training alone.


Local Renin-Angiotensin system in the reproductive system.
The renin-angiotensin system (RAS) is well known as regulator of electrolytes and blood pressure. Besides this function, there are numerous studies supporting the idea of a local tissue RAS. This system controls the local activity of the different RAS family members, especially of the functional proteins Angiotensin II and Angiotensin (1-7). Those antagonistically acting proteins have been described to be expressed in different organ systems including the human reproductive tract. Therefore, this local RAS has been suspected to be involved in the control and regulation of physiological and pathological conditions in the female reproduction tract. This review of the available literature summarizes the physiological influence of the RAS on the follicular development, ovarian angiogenesis, and placental- and uterine function. In addition, in the second part the role of the RAS concerning ovarian- and endometrial cancer becomes elucidated. This section includes possible novel therapeutic strategies via inhibition of RAS-mediated tumor growth and angiogenesis. Looking at a very complex system of agonistic and antagonistic tissue factors, it may be supposed that the RAS in the female reproduction tract will be of rising scientific interest in the upcoming years.


Percent framing attenuates the magnitude effect in a preference-matching task of intertemporal choice.
Research in intertemporal decisions shows that people value future gains less than equivalent but immediate gains by a factor known as the discount rate (i.e., people want a premium for waiting to receive a reward). A robust phenomenon in intertemporal decisions is the finding that the discount rate is larger for small gains than for large gains, termed the magnitude effect. However, the psychological underpinnings of this effect are not yet fully understood. One explanation proposes that intertemporal choices are driven by comparisons of features of the present and future choice options (e.g., information on rewards). According to this explanation, the hypothesis is that the magnitude effect is stronger when the absolute difference between present and future rewards is emphasized, compared to when their relative difference is emphasized. However, this hypothesis has only been tested using one task (the two-choice paradigm) and only for gains (i.e., not losses). It's therefore unclear whether the findings that support the hypothesis can be generalized to different methodological paradigms (e.g., preference matching) and to the domain of losses. To address this question, we conducted experiments using the preference-matching method whereby the premium amounts that people could ask for were framed in terms of either currencies (emphasizing absolute differences) or percentages (emphasizing relative differences). We thus tested the robustness of the evidence in support of the hypothesis that percent framing, relative to currency framing, attenuates the magnitude effect in the domain of gains (Studies 1, 2, and 3) and in the domain of losses (Study 1, 3, and 4). The data were heavily skewed and the assumption of equal variances was violated. Therefore, in place of parametric statistical tests, we calculated and interpreted parametric and nonparametric standardized and unstandardized effect size estimates and their confidence intervals. Overall, the results support the hypothesis.


Invasion and diversity in Pseudomonas aeruginosa urinary tract infections.
Introduction. P. aeruginosa is an opportunistic Gram-negative pathogen frequently isolated in urinary tract infections (UTI) affecting elderly and catheterized patients and associated with ineffective antibiotic treatment and poor clinical outcomes.Gap statement. Invasion has been shown to play an important role in UTI caused by E. coli but has only recently been studied with P. aeruginosa. The ability of P. aeruginosa to adapt and evolve in chronic lung infections is associated with resistance to antibiotics but has rarely been studied in P. aeruginosa UTI populations.Aim. We sought to determine whether phenotypic and genotypic heterogeneity exists in P. aeruginosa UTI isolates and whether, like urinary pathogenic Escherichia coli, these could invade human bladder epithelial cells - two factors that could complicate antibiotic treatment.Methodology. P. aeruginosa UTI samples were obtained from five elderly patients at the Royal Liverpool University Hospital as part of routine diagnostics. Fourty isolates from each patient sample were screened for a range of phenotypes. The most phenotypically diverse isolates were genome sequenced. Gentamicin protection assays and confocal microscopy were used to determine capacity to invade bladder epithelial cells.Results. Despite significant within-patient phenotypic differences, no UTI patient was colonized by distinct strains of P. aeruginosa. Limited genotypic differences were identified in the form of non-synonymous SNPs. Gentamicin protection assays and confocal microscopy provided evidence of P. aeruginosa's ability to invade bladder epithelial cells.Conclusions. Phenotypic variation and cell invasion could further complicate antibiotic treatment in some patients. More work is needed to better understand P. aeruginosa UTI pathogenesis and develop more effective treatment strategies.