Versatile and cooperative reactivity of a triruthenium polyhydride cluster. A computational study.
The reaction of a trinuclear polyhydride complex Ru3H5(C5H5)3 with cyclopentadiene, C5H6, has been studied computationally. A mechanism for the experimentally observed selective C-C bond activation is proposed. All three Ru centers participate in various steps of the mechanism. The catalytic involvement of two cluster hydrides in the transformation of the C5Hn fragment is emphasized.


Oncostatin M and IL-6 induce u-PA and VEGF in prostate cancer cells and correlate in vivo.
Oncostatin M (OSM) and interleukin-6 (IL-6) are growth factors for prostate cancer (PC). Vascular endothelial growth factor (VEGF) and urokinase-type plasminogen-activator (u-PA) have been implicated in tumour progression. A possible interaction between IL-6, OSM, u-PA and VEGF in PC was investigated. Primary prostate epithelial cells (PPEC) and DU-145 PC cells were treated with IL-6 or OSM and the effects on u-PA and VEGF expression were studied. Plasma levels of IL-6, OSM, u-PA and VEGF were determined in patients with or without PC. In DU-145 cells, OSM and IL-6 up-regulated u-PA and VEGF significantly. Higher levels of IL-6 and OSM in metastasising PC than in nonmetastasising PC and benign prostatic hyperplasia (BPH) and correlations between IL-6, OSM, u-PA and VEGF were found. OSM and IL-6 increase u-PA and VEGF in DU-145 cells but not in PPEC and possibly, by promoting matrix degradation and angiogenesis, could play a role in the pathogenesis of prostate cancer.


Some insights into the possible development of a biosynthetic pathway and biological function for anthramycin in Streptomyces refuineus.
Using anthramycin, a potent antitumor antibiotic produced by Streptomyces refuineus, as an example, we have developed a rational model for the evolution of the capability of this microorganism to produce, tolerate and retain the genetic information needed to make this extremely potent secondary metabolite. The concepts and ideas outlined in this article have also been applied in a more general way to other antibiotics with the hope that this might stimulate research designed to test some of these concepts.


Obesity survival paradox in pneumonia: a meta-analysis.
It is unclear whether an 'obesity survival paradox' exists for pneumonia. Therefore, we conducted a meta-analysis to assess the associations between increased body mass index (BMI), pneumonia risk, and mortality risk. Cohort studies were identified from the PubMed and Embase databases. Summary relative risks (RRs) with their corresponding 95% confidence intervals (CIs) were calculated using a random effects model. Thirteen cohort studies on pneumonia risk (n = 1,536,623), and ten cohort studies on mortality (n = 1,375,482) were included. Overweight and obese individuals were significantly associated with an increased risk of pneumonia (RR = 1.33, 95% CI 1.04 to 1.71, P = 0.02, I(2) = 87%). In the dose-response analysis, the estimated summary RR of pneumonia per 5 kg/m(2) increase in BMI was 1.04 (95% CI 1.01 to 1.07, P = 0.01, I(2) = 84%). Inversely, overweight and obese subjects were significantly associated with reduced risk of pneumonia mortality (RR = 0.83, 95% CI 0.77 to 0.91, P < 0.01, I(2) = 34%). The estimated summary RR of mortality per 5 kg/m(2) increase in BMI was 0.95 (95% CI 0.93 to 0.98, P < 0.01, I(2) = 77%). This meta-analysis suggests that an 'obesity survival paradox' exists for pneumonia. Because this meta-analysis is based on observational studies, more studies are required to confirm the results.


Patient-reported outcomes and quality of life measures in atopic dermatitis.
Atopic dermatitis (AD) is a complex and heterogeneous disorder with a profound symptom burden and harmful impact on multiple domains of quality of life (QOL). Many different patient-reported outcome (PRO) measures exist to assess clinical manifestations and QOL impairment in AD, but none comprehensively assess all aspects of the disease. This review addresses the PRO and QOL measures currently used in AD and their properties, strengths, weaknesses, and feasibility for assessing AD in randomized controlled trials and clinical practice. Currently, the patient-oriented eczema measure (POEM) has emerged as a preferred PRO for AD clinical manifestations, though no single instrument has developed as a preferred QOL measure. Validated PRO and QOL measures should be incorporated in all clinical trials of AD and in clinical practice where feasible.


From BDNF to reading: Neural activation and phonological processing as multiple mediators.
The BDNF gene is a prominent promoter of neuronal development, maturation and plasticity. Its Val66Met polymorphism affects brain morphology and function within several areas and is associated with several cognitive functions and neurodevelopmental disorder susceptibility. Recently, it has been associated with reading, reading-related traits and altered neural activation in reading-related brain regions. However, it remains unknown if the intermediate phenotypes (IPs, such as brain activation and phonological skills) mediate the pathway from gene to reading or reading disability. By conducting a serial multiple mediation model in a sample of 94 children (age 5-13), our findings revealed no direct effects of genotype on reading. Instead, we found that genotype is associated with brain activation in reading-related and more domain general regions which in turn is associated with phonological processing which is associated with reading. These findings suggest that the BDNF-Val66Met polymorphism is related to reading via phonological processing and functional activation. These results support brain imaging data and neurocognitive traits as viable IPs for complex behaviors.


Age-related changes in fibre differentiation of rat lens epithelial cells in vitro.
Epithelial cells in explants from rat lenses differentiate into fibre cells when cultured with retina conditioned medium (RCM). This differentiation is characterised by cell elongation, the accumulation of alpha-crystallin and the onset of synthesis of the fibre specific beta- and gamma-crystallins. To determine the effect of donor age on the synthesis of beta- and gamma-crystallins in response to culture with RCM, we explanted lens epithelia from 3-, 10- and 21-day-old rats. Explants were trimmed to obtain a population of central epithelial cells and at the end of the culture period crystallin content was measured by ELISA methods and expressed per unit DNA. Explants from 3- and 10-day-old rats showed significant increases in the levels of beta-crystallin/DNA within four days after the addition of RCM. The synthesis of beta-crystallin in explants from 21-day-old rats was delayed until after day 4 of culture, but rose quickly to reach the same levels at 10 days as the explants from younger lenses. The ability of lens epithelia to synthesise gamma-crystallin in response to RCM showed a dramatic decline as the age of the donor rat increased. After 10 days of culture, explants from 10-day-old rats contained only 12% of the amount of gamma-crystallin accumulated by explants from 3-day-old rats. Explants from 21-day-old rats accumulated no significant gamma-crystallin until day 10 of culture, and at this time the amount was significantly less than that accumulated by explants from younger rats.(ABSTRACT TRUNCATED AT 250 WORDS)


Role of receptor occupancy in the transition from responsive to unresponsive states in cultured breast tumor cells.
Progression from a steroid sensitive to insensitive state is characteristic of breast tumors, but little is known about the molecular mechanisms involved. Changes in steroid receptor can be associated with the progression. This paper reviews the cell culture data pertaining to loss of response and concludes that loss of receptor is a consequence rather than a cause of insensitivity. This view is based on evidence that loss of all response parameters occurs despite the presence of fully functional receptors as determined by transfection experiments. The postreceptor defect appears to be at the level of the hormone response element of the responsive genes and may involve DNA methylation. The implications of the model for human breast cancer biology are discussed.


Recent developments in immunotherapy of cancers caused by human papillomaviruses.
A subset of oncogenic human papillomaviruses (HPVs) is the main cause of genital cancers, most importantly cervical cancer and an increasing number of head and neck cancers. Despite the availability of prophylactic vaccines against the most prevalent oncogenic HPV types, HPV-induced malignancies are still a major health and economic burden. Besides conventional treatment with surgery, chemotherapy and radiation, immunotherapy is emerging as an efficient adjuvant option. Here, we review relevant studies and ongoing clinical trials using immune checkpoint inhibitors, therapeutic vaccines, gene editing approaches and adoptive T cell therapies, with special focus on engineered TCR T cells, which are showing encouraging results and could lead to significant improvement in the treatment of HPV+-infected cancer patients.


Diving medicine.
This article orients the practicing physician to the physical and physiologic basis for the more common medical problems encountered in diving, discusses the common presenting manifestations for these disorders, and provides a framework for their treatment. Medical fitness for diving is also briefly addressed.


Evaluation of the effects of bredemolic acid on selected markers of glucose homeostasis in diet-induced prediabetic rats.
Pentacyclic triterpenes (such as maslinic acid) are natural anti-diabetic agents that ameliorate glucose metabolism in diet-induced prediabetes. However, the effects of bredemolic acid (BA), maslinic acid isomer, is yet unknown in prediabetic (PD) conditions. To investigate the effects of BA on some glucose homeostasis parameters in high-fat high-carbohydrate (HFHC) diet-induced PD rats. Thirty-six (36) male rats (150-180 g) were divided into two groups, the normal diet (ND) non-prediabetic, NPD (n = 6) and the HFHC diet PD groups (n = 30). The PD animals were further sub-divided into five groups (n = 6) where they were treated with BA for 12 weeks while monitoring changes in blood glucose, caloric intake, and body weight. Diet-induced prediabetes resulted in increased body weight, caloric intake, glycated haemoglobin, and glucose tolerance. BA treatment ameliorated glucose tolerance, lowered plasma insulin and increased expression of glucose transporter 4 (GLUT 4) in rats. BA administration restored glucose homeostasis in diet-induced prediabetes regardless of diet intervention.


Serum endocan levels in patients with habitual abortion.
The aim of this study was to investigate whether there is a new factor in the etiology of recurrent loss of pregnancy. For this purpose, serum malondialdehyde (MDA) and nitric oxide (NO) levels as indicators of oxidative stress, and endocan levels, a marker of vascular dysfunction, were investigated in patients diagnosed with habitual abortion. The research was conducted as a prospective case-control study. Patients aged 18-40 years with two or more consecutive pregnancy losses revealed by ultrasonographic or histopathological examination, and with no pathology capable of causing habitual abortion were included in the study group. Patients with no history of abortion, with at least one healthy pregnancy, who were planning pregnancies, and who presented to the outpatient clinic for routine prepregnancy tests were selected as the control group. Two groups were established-habitual abortion (n = 30) and control (n = 29). At the end of the menstrual cycle, blood samples were collected and centrifuged. Serum NO, MDA, and endocan levels were studied. Serum endocan, NO, and MDA levels were higher in women with habitual abortion compared to healthy controls. Pearson's correlation analysis revealed a positive correlation between serum endocan levels and NO and MDA levels. A positive correlation was also observed between serum MDA and NO levels. Multiple regression was run to predict serum endocan levels from MDA and NO levels. These variables emerged as statistically significant predictors of endocan. These findings suggest the presence of vascular endothelial dysfunction in patients with habitual abortion.


Conformational transitions of alpha-elastin.
The alpha-elastin, the soluble product obtained from elastin by oxalic acid hydrolysis, has been studied from a conformational point of view in different conditions using circular dichroism spectroscopy. The spectral variations of the alpha-elastin dissolved in water and in different organic solvents/water mixtures have been examined in order to establish the effect of the solvents on the structural properties of the protein. The effect of calcium ions has also been studied on alpha-elastin dissolved either in water or in organic solvents. Finally, the effect of pH and temperature on the conformational properties of the alpha-elastin has been investigated.


Detection of Circulating Tumor DNA in the Blood of Cancer Patients: An Important Tool in Cancer Chemoprevention.
Liquid biopsies represent novel promising tools to determine the impact of clonal heterogeneity on clinical outcomes with the potential to identify novel therapeutic targets in cancer patients. We developed a low-coverage whole-genome sequencing approach in order to noninvasively establish copy number aberrations in plasma DNA from metastasized cancer patients. Using plasma-Seq we were able to monitor genetic evolution including the acquirement of novel copy number changes, such as focal amplifications and chromosomal polysomies. The big advantage of our approach is that it can be performed on a benchtop sequencer, speed, and cost-effectiveness. Therefore, plasma-Seq represents an easy, fast, and affordable tool to provide the urgently needed genetic follow-up data. Here we describe our method including plasma DNA extraction, library preparation, and bioinformatic analyses.


Coordinating fingerprint determination of solid-phase microextraction/gas chromatography-mass spectrometry and chemometric methods for quality control of oxidized tallow.
Based on optimized solid-phase microextraction/gas chromatography-mass spectrometry (SPME/GC-MS) and chemometric methods, simple, reliable and reproducible methods were described for the first time for developing a chromatographic fingerprint of oxidized tallow. Eight optimal oxidized tallow samples were used to establish the chromatographic fingerprint. Spectral correlative chromatogram was adopted to identify 33 "common components". The validation of fingerprint analysis was performed based on the relative retention time, the relative peak area of common peaks, sample stability and similarity analysis. The correlation coefficient of similarity of eight optimal oxidized tallow samples was more than 0.962, which showed that samples from different batches were consistent to some extent in spite of slightly different chemical indexes. Through principal component analysis (PCA), 14 constituents were further screened out to be the main chemical markers, which could be applied to more accurate quantitative discrimination and quality control of oxidized tallow.


Analysis in vivo of the bacteriophage P22 headful nuclease.
Bacteriophage P22 packages its double-stranded DNA chromosomes from concatemeric replicating DNA in a processive, sequential fashion. According to this model, during the initial packaging event in such a series the packaging apparatus recognizes a nucleotide sequence, called pac, on the DNA, and then condenses DNA within the coat protein shell unidirectionally (rightward) from that point. DNA ends are generated near the pac site before or during the condensation reaction. The right end of the mature chromosome is created by a cut made in the DNA by the "headful nuclease" after a complete chromosome is condensed within the phage head. Subsequent packaging events on that concatemeric DNA begin at the end generated by the headful cut of the previous event and proceed in the same direction as the previous event. We report here accurate measurements of the P22 chromosome length (43,400( +/- 750) base-pairs, where the uncertainty is the range in observed lengths), genome length (41,830( +/- 315) base-pairs, where the uncertainty represents the accuracy with which the length is known), the terminal redundancy (1600( +/- 750) base-pairs or 3.8( +/- 1.8)%, where the uncertainty is the observed range) and the imprecision in the headful measuring device ( +/- 750 base-pairs or +/- 1.7%). In addition, we present evidence for a weak nucleotide sequence specificity in the headful nuclease. These findings lend further support to, and extend our understanding of, the sequential series model of P22 DNA packaging.


Audit of the radiotherapy in the DBCG 82 b&c trials--a validation study of the 1,538 patients randomised to postmastectomy radiotherapy.
In the DBCG 82 b&c trials 3083 patients with stages II and III breast cancer were randomised to receive postmastectomy radiotherapy (RT) versus no RT in addition to systemic therapy. The study showed a decrease in loco-regional recurrences and an improved survival in patients receiving RT. The aim of the present study was to describe the delivered RT for the 1538 patients who were randomised to RT, and to evaluate the compliance with the RT guidelines. Basic information about the given RT was recorded in the DBCG data centre. For the current study, missing and additional information was collected from individual RT treatment charts. We defined some criteria for complying with the DBCG RT guidelines regarding target coverage and dose and fractionation and based on that we also defined some criteria for having clinically acceptable RT treatments. Of the 1538 patients, 87% received megavoltage RT, 8% had orthovoltage RT and 5% never began or completed RT. Of the 1341 megavoltage irradiated patients, the guideline compliance regarding target coverage of the axillary/periclaviculary region, internal mammary nodes and chest wall was 88, 79 and 85%, respectively. Only 0, 0.2 and 0.4% did not have clinically acceptable target coverage. The dose and fractionation was according to the guidelines in 96% and none had clinically unacceptable dose and fractionation schedules. The guideline compliance for megavoltage RT was high with 88, 79 and 85% complying with the guidelines regarding target coverage of the axillary/periclaviculary region, internal mammary nodes and chest wall, respectively, and with 96% complying with the guidelines regarding dose and fractionation schedules. Less than 1% had clinically unacceptable target coverage and none had unacceptable dose and fractionation schedules.


Outbreak of a South West Pacific clone Panton-Valentine leucocidin-positive meticillin-resistant Staphylococcus aureus infection in a UK neonatal intensive care unit.
Panton-Valentine leucocidin-positive meticillin-resistant Staphylococcus aureus (PVL-MRSA) has become a globally common cause of community-acquired infections. We report an outbreak of PVL-MRSA in a regional neonatal unit in the UK involving three babies and three staff members. Quinolone susceptibility was helpful in identifying potential PVL-MRSA but toxin gene profiling and sequence-based typing were required to distinguish between two PVL-MRSA strains present in the unit. All three symptomatic babies and two staff carriers, one of whom was symptomatic, were found to be carrying the South West Pacific (SWP) clone of PVL-MRSA (ST30). One of the staff carriers had recently visited the Philippines and was thought to be the source of the outbreak. Control was established using standard infection control procedures but one baby with relapsing MRSA colonization has required more than 100 days in isolation. This is the first reported neonatal outbreak associated with the SWP clone in the UK. Our study highlights the potential risk of further introductions of this organism by healthcare staff or patients epidemiologically linked with the Philippines.


Reliability and validity of active, passive and dynamic range of motion tests.
The purposes of this project were to determine (a) the reliability of ROM and POM assessment methods for tests where an ankle joint brace was used and (b) the relationship between active and passive ROM and POM inversion measurements. The range of motion of the ankle joint complex for inversion was quantified using a range of motion apparatus. The inversion path of motion for the foot and the shoe was quantified using a high speed video system. The results of this study indicated: (a) Comprehensive functional tests of ankle joint braces using ROM and POM measurements showed maximal group differences of less than 1 degree between days for ROM (rAROM = 0.96 and rPROM = 0.93) and less than 1.5 degrees for POM measurements (rPOM = 0.88). (b) PROM measurements showed a consistent "creep" effect of about 2 degrees with increasing trial number during the first ten trials which must be taken into consideration for the design of the appropriate test protocol. (c) The correlation coefficient between AROM and POM was 0.37 and 0.44 between PROM and POM, suggesting that AROM and PROM measurements do not predict inversion during actual movement.


Left ventricular function during sepsis.
The prevalence and prognostic significance of left ventricular involvement in septic patients without shock was investigated. Systolic time intervals (STI) and preejection period/left ventricular ejection time ratio (PEP/LVET) were used to assess left ventricular function. Forty-nine patients, 22 of whom ultimately died, were studied. The group as a whole showed abnormal PEP/LVET ratio (0.40 +/- 0.02) that differed significantly (p less than .01) from reported normal values (0.345 +/- 0.002), demonstrating widespread left ventricular dysfunction in this population. In order to establish the prognostic significance of left ventricular impairment, the population was divided into two groups according to the PEP/LVET ratio. Group 1 (PEP/LVET less than or equal to 0.42) showed a mortality rate of 10/33 (30%), while group 2 (PEP/LVET greater than 0.42) had a significantly greater mortality (12/16 [75%], p less than .001). The test that has a sensitivity of 55%, a specificity of 85%, and a positive predictive value of 75% identifies a subset of septic patients with severe impairment of left ventricular function and high risk of dying.


The Spear Horizon: First spatial analysis of the Schöningen site 13 II-4.
The Spear Horizon (Schöningen 13 II-4) from Schöningen, Lower Saxony, Germany, is one of the most important archeological sites dating to the Middle Pleistocene. Until today, the numerous finds have only been published individually, often outside of their context. Here we present for the first time the distribution map of the Spear Horizon together with a spatial analysis of the different categories of remains (flint, bones, and woods). The finds are situated in a 10 m wide belt, which runs parallel to a former lakeshore. The distribution of faunal remains correlates closely with the distribution of flint artifacts and wooden objects. We have been able to distinguish five different sectors that can be aligned with different events or activities. The greatest density of finds was evident within an area of 11 × 15 m, where most of the horse skulls were recovered. Some of the square meters contain more than 150 finds. During the excavation the profiles were continually documented and these data help us to reconstruct the shoreline of the paleo-lake with considerable accuracy. Over a distance of 60 m, the thickness and density of the organic mud and peat layers could be reconstructed in high resolution. The distribution of finds shows no preferred orientation or selection through size. The analyses only indicate small-scale dislocations and limited taphonomic alterations. The fraction of lithic artifacts with size ranges less than 2 cm are preserved, while some smaller bone fragments are missing. Most of the wooden artifacts are in-situ, but were deformed by the ice load during the Saalian ice age. While some small charcoal remains as well as a burnt artifact have been observed, there is no evidence of burnt bones. Our results allow a first insight into the formation history of the site.


Subtemporal Approach for Gross Total Resection of Retrochiasmatic Craniopharyngiomas: Our Experience on 30 Cases.
Surgical treatment of retrochiasmatic craniopharyngiomas is associated with higher rates of complications, mortality, failure of complete removal, and recurrence compared with craniopharyngiomas located elsewhere. These tumors lie behind the optic chiasm and when large can extend upward into the third ventricle and downward along the brain stem, making their adequate exposure challenging. Most of the proposed techniques either use a translamina terminalis route or require wide bony exposures. In this study, we assessed the feasibility of a subtemporal approach for achieving gross total resection of retrochiasmatic craniopharyngiomas. Thirty patients with retrochiasmatic craniopharyngioma underwent surgery via a subtemporal approach. The technique and surgical and preoperative and postoperative endocrinologic outcomes are described in detail. Gross total resection was achieved in all cases. The average tumor volume was 7.59 mL. The average postsurgical observation time was 73.8 months. During this time, 3 recurrences were observed (10.7%). The perioperative mortality was 6.6%. The pituitary stalk was preserved in 13 cases. Partial preservation of the pituitary stalk did not offer any advantage in terms of pituitary function. No postoperative vision worsening or new fixed neurologic deficits were observed. Among the 22 patients with preoperative vision impairment, 18 reported a significant improvement. The most common abnormalities within the temporal lobe on the side of the exposure seen on control magnetic resonance imaging were mild temporal horn enlargement (13 cases) and T2 hyperintensity (7 cases). A subtemporal approach can be an attractive alternative approach to accessing retrochiasmatic craniopharyngiomas. Outcomes are comparable to those associated with other widely used and time-consuming exposures.


Consistency of Bayesian inference of resolved phylogenetic trees.
Bayesian inference is now a leading technique for reconstructing phylogenetic trees from aligned sequence data. In this short note, we formally show that the maximum posterior tree topology provides a statistically consistent estimate of a fully resolved evolutionary tree under a wide variety of conditions. This includes the inference of gene trees from aligned sequence data across the entire parameter range of branch lengths, and under general conditions on priors in models where the usual 'identifiability' conditions hold. We extend this to the inference of species trees from sequence data, where the gene trees constitute 'nuisance parameters', as in the program (*)BEAST. This note also addresses earlier concerns raised in the literature questioning the extent to which statistical consistency for Bayesian methods might hold in general.


Hematopoietic growth factors and acute leukemia.
Over the past decade, with the advent of hematopoietic growth factors, major strides have been made and multiple studies have attempted to define the use of these cytokines in acute leukemia. It is perhaps disappointing that, after so many studies, so many questions remain. Nevertheless, the role of cytokines in induction therapy seems to be established, although questions remain around the issue of priming therapy. Intriguing data regarding the potential for enhancing antimicrobial function should hopefully be resolved over the next few years. What is perhaps most reassuring is that the issue of safety, which for a considerable period of time precluded the development of clinical trials in acute leukemia, has been firmly laid to rest. The use of growth factors to protect normal stem cells during treatment of leukemia and to induce leukemic cell differentiation has not yet been the subject of many clinical trials. Also, growth factors are likely targets for the interruption of autocrine leukemic blast or progenitor cell growth, but again, few clinical observations are published. With the ongoing cloning of new growth factors active both in normal hematopoiesis and in leukemogenesis, the role of growth factor use in the treatment of AML will likely be the basis for much future preclinical and clinical activity.


Validation of a single-channel airflow monitor for screening of sleep-disordered breathing.
A simple screening method for sleep-disordered breathing (SDB) is desirable for primary care practices. In the present study, a simple monitor, which utilises a new type of flow sensor and a novel algorithm, was prospectively validated. Home recording for 2 nights with the monitor only, followed by in-laboratory recording with the monitor together with polysomnography, were carried out in consecutive patients (n = 100) suspected of SDB. A subjective sleep log was also recorded. The signal was analysed using power spectral analysis, which yielded the flow respiratory disturbance index (flow-RDI). There was no recording failure at home. The reproducibility of the flow-RDI between the 2 nights at home was high (intraclass correlation coefficient = 0.92). The sensitivity and specificity of the in-laboratory flow-RDI to diagnose SDB were 0.96 and 0.82, 0.91 and 0.82, and 0.89 and 0.96, for apnoea/hypopnoea index (AHI) > or =5, > or =15 and > or =30 events x h(-1), respectively. The diagnostic ability in low-severity subgroups (female, normal weight, AHI <15 events x h(-1)) was almost comparable to that in the entire group. Excluding subjective waking time on the sleep log from the recording time had no significant effect on the flow-RDI. The single-channel monitor is considered feasible for ambulatory sleep disordered breathing monitoring because of its easy applicability, high reproducibility and relatively high agreement with polysomnography results.


The increase in hexokinase activity in hereditary avian muscular dystrophy.
Hexokinase activity was found to be increased in both the more severely affected red (thigh) muscle of dystrophic chickens. The increase in activity was largely associated with the particulate fraction. These findings may indicate early events in the pathogenesis of avian muscular dystrophy.


Actions of platelet-derived growth factor isoforms in mesangial cells.
Platelet-derived growth factor (PDGF) occurs as homodimers or heterodimers of related polypeptide chains PDGF-BB, -AA, and -AB. There are two receptors that bind PDGF, termed alpha and beta. The beta receptor recognizes PDGF B chain and is dimerized in response to PDGF BB. The alpha receptor recognizes PDGF B as well as A chains and can be dimerized by the three dimeric forms of PDGF AA, AB, and BB. To characterize PDGF receptor signaling mechanisms and biologic activities in human mesangial cells (MC), we explored the effects of the three PDGF isoforms on DNA synthesis, phospholipase C activation, and PDGF protooncogene induction. PDGF-BB homodimer and AB heterodimer induced a marked increase in DNA synthesis, activation of phospholipase C, and autoinduction of PDGF A and B chain mRNAs, whereas PDGF-AA homodimer was without effect. The lack of response to PDGF AA could be accounted for by down-regulation of the PDGF-alpha receptor since preincubation of MC with suramin restored PDGF AA-induced DNA synthesis. Ligand binding studies demonstrate specific binding of labeled PDGF BB and AB and to a lower extent PDGF AA isoforms to mesangial cells. These results are consistent with predominant expression of PDGF beta receptor in MC, which is linked to phospholipase-C activation. The potent biologic effects of PDGF-AB heterodimer in cells that express very few alpha receptors and do not respond to PDGF AA are somewhat inconsistent with the currently accepted model of PDGF receptor interaction and suggest the presence of additional mechanisms for PDGF isoform binding and activation.


Evolution of extracellular enzyme activities during manure composting.
The objectives of this work were to determine the extracellular enzyme profiles during composting, relate the activities of these enzymes to the changes in microbial population and compare the enzyme profiles between two manures. API ZYM assay was used to monitor the activities of 19 extracellular enzymes during poultry and pig manure composting. Results showed an overall increase in diversity and relative abundance of enzymes present. The relative abundance and activities of enzymes were higher in poultry manure than in pig manure. Among the 19 enzymes tested, esterase, valine amino-peptidase and alpha-galactosidase were the most abundant enzymes in poultry manure, whereas it was N-acetyl-beta-glucosaminidase for the pig manure. A number of these enzymes correlated with change in numbers of different microbial groups during composting. The composting process represented a combined activity of a wide succession of environments, as one enzyme/microbial group overlapped the other and each emerged gradually due to the continual change in temperature and progressive breakdown of complex compounds to simpler ones. The results presented here show the applicability of the API ZYM test not only in monitoring the quantitative and qualitative fluctuation of the available substrate during composting, but also in revealing differences in composts and compost maturity.


Effect of Intramyocardial Grafting Collagen Scaffold With Mesenchymal Stromal Cells in Patients With Chronic Ischemic Heart Disease: A Randomized Clinical Trial.
Cell therapy may be helpful for cardiac disease but has been fraught with poor cell retention and survival after transplantation. To determine whether cell-laden hydrogel treatment is safe and feasible for patients with chronic ischemic heart disease (CIHD). This randomized, double-blind clinical trial was conducted between March 1, 2016, and August 31, 2019, at a single hospital in Nanjing, China. Among 115 eligible patients with CIHD, 50 patients with left ventricular ejection fraction of 45% or less were selected to receive elective coronary artery bypass grafting (CABG) and additionally randomized to cell-plus-collagen treatment (collagen/cell group), cell treatment alone (cell group), or a control group. Sixty-five patients were excluded because of severe comorbidities or unwillingness to participate. Forty-four participants (88%) completed the study. The last patient completed 12 months of follow-up in August 2019. Analyses were prespecified and included all patients with available data. During CABG, patients in the collagen/cell group were treated with human umbilical cord-derived mesenchymal stromal cell (hUC-MSC)-laden collagen hydrogel intramyocardial injection, and the cell group was treated with hUC-MSCs alone. Patients in the control group underwent CABG alone. The primary outcome was safety of the cell-laden collagen hydrogel assessed by the incidence of serious adverse events. The secondary end point was the efficacy of treatment, according to cardiovascular magnetic resonance imaging-based left ventricular ejection fraction and infarct size. Fifty patients (mean [SD] age, 62.6 [8.3] years; 38 men [76%]) were enrolled, of whom 18 were randomized to the collagen/cell group, 17 to the cell group, and 15 to the control group. Patient characteristics did not differ among groups at baseline. For the primary end point, no significant differences in serious adverse events, myocardial damage markers, and renal or liver function were observed among all groups after treatment; the collagen/cell and cell groups each had 1 case of hospitalization because of heart failure, and no serious adverse events were seen in the control group. At 12 months after treatment, the mean infarct size percentage change was -3.1% (95% CI, -6.20% to -0.02%; P = .05) in the collagen/cell group, 5.19% (-1.85% to 12.22%, P = .35) in the cell group, and 8.59% (-3.06% to 20.25%, P = .21) in the control group. This study provides, to our knowledge, the first clinical evidence that the use of collagen hydrogel is safe and feasible for cell delivery. These findings provide a basis for larger clinical studies. ClinicalTrials.gov Identifier: NCT02635464.


Comparison of a ray-tracing refractometer, autorefractor, and computerized videokeratography in measuring pseudophakic eyes.
To test the accuracy and reliability of the first-generation prototype of Tracey-1, a ray-tracing refractometer. Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, USA. The refractive spherical equivalent (SE) and astigmatism measured by Tracey-1, subjective manifest refraction (MR), and autorefraction (AR) (Nidek AR-3300) were compared in 58 pseudophakic eyes of 44 patients with a mean age of 69.95 years +/- 8.6 (SD). The astigmatic values obtained from Tracey-1 and computerized videokeratography were also compared. Astigmatism values were compared using power vector analysis. The mean SEs measured by MR, Tracey, and AR were -0.76 diopter (D) +/- 0.96 (SD) (range 1.00 to -3.00 D), 0.37 +/- 0.64 D (range 1.68 to -1.49 D), and -0.44 +/- 1.13 D (range 1.63 to -3.50 D), respectively. The Pearson correlation coefficients between MR and Tracey values and between MR and AR values were high (r = 0.895 and r = 0.875, respectively; both P < .0001). However, the mean difference between the Tracey and MR values was 1.13 +/- 0.48 D (range 2.45 to -0.06 D) (P < .001). The mean cylindrical differences between MR and Tracey and between MR and AR were 0.03 +/- 0.51 D (range 1.22 to -1.07 D) (P = .709) and -0.30 +/- 0.62 D (range 0.50 to -2.25 D) (P = .003), respectively. Power vector analysis revealed difference vectors of -0.16 x 60 between Tracey and MR and -0.22 x 87 between AR and MR. Spherical and cylindrical refractive data obtained with the Tracey system correlated well with those derived from MR; however, there was a mean spherical error of approximately 1.10 D. Further work is required to refine the accuracy and range of this device.


ETV6 (TEL)-AML1 pre-B acute lymphoblastic leukaemia cells are associated with a distinct antigen-presenting phenotype.
The recently recognized translocation t(12;21)(p13;q22), which results in the ETV6-AML1 fusion product, is the most common genetic rearrangement found in childhood pre-B acute lymphoblastic leukaemia (ALL). It has been associated with a more favourable prognosis and a distinct immunophenotype in terms of myeloid and B cell-associated antigen expression. Using flow cytometry, we investigated whether the unique ETV6-AML1 phenotype extended to molecules associated with antigen presentation by analysing 50 diagnostic bone marrow samples from paediatric pre-B ALL patients. Reverse transcription polymerase chain reaction for the ETV6-AML1 fusion transcript was positive in 14 patients. ETV6-AML1-positive samples were characterized by a significantly higher expression of the co-stimulatory molecule CD40 (P < 0.0001), as well as a significantly higher class II HLA-DR mean channel fluorescence (P = 0.001). In contrast, CD86 expression was significantly lower on fusion-positive samples (P = 0.010) while there was no difference in expression of CD80 or major histocompatibility complex class I between ETV6-AML1-positive and -negative samples. This is the first observation in acute leukaemia that the distinct immunophenotype associated with specific translocations includes the expression of molecules associated with antigen presentation. In the case of ETV6-AML1 pre-B ALL, this characteristic immunophenotype may have implications for the immunogenicity of the leukaemic cells.


The effects of stenosis severity on the hemodynamic parameters-assessment of the correlation between stress phase angle and wall shear stress.
To study the effects of increase in the degree of stenosis severity and subsequent complexity of hemodynamic patterns on hemodynamic parameters, experimental investigations and numerical simulations were performed. The correlations between the large negative Stress Phase Angle (SPA), the low mean Wall Shear Stress (WSS) and high Oscillatory Shear Index (OSI) were investigated at the distal shoulder and post-stenotic regions as the outcomes of elevated stenosis severity. Models included non-Newtonian fluid flow in stenotic arteries with 30-80% symmetrical stenoses. To study the interactions between pulsatile WSS and pulsatile wall circumferential stress (WCS) acting on endothelial cells, SPA as the phase difference between WSS and WCS waves was used. Moreover, the distribution of SPA on the lumen axis was compared to the distributions of the mean WSS and OSI that have been regarded until now as the determinants of atherosclerosis-prone regions. Results indicate that an increase in stenosis severity, not only affects the mean WSS, mean WCS and pulse amplitudes, but also influences the phase difference between them. The SPA is large negative on the distal shoulder and post-stenotic areas where atherosclerotic plaque develops. The increasing stenosis severity and the subsequent increasing complexity of hemodynamic patterns affect the correlation between any of the low mean WSS and high OSI with large negative SPA, such that it not only leads to create and develop some regions where the correlation between any of the low mean WSS and high OSI with large negative SPA is well but also leads to create and develop other regions where such correlations fail.


[Geographic distribution of hematologic elements in Central African countries: distribution of the ABO blood group system].
1,559 people of various ethnical and geographical origin from the Central African Republic (CAR) have been tested for A, B, O group determination. Genic repartition is analysed, historic implications in human migrations are discussed.


Pharmacokinetics, mass balance, and induction potential of a novel GABA uptake inhibitor, CI-966 HCl, in laboratory animals.
CI-966 exhibits anticonvulsant properties in various animal models. The drug acts by inhibiting synaptic uptake of gamma-aminobutyric acid (GABA). Oral absorption of CI-966 in dogs given 1.39 mg/kg is rapid with a tmax of 0.7 hr. In rats given 5 mg/kg oral, a mean tmax of 4.0 hr was observed. Following iv administration of the same respective doses, elimination t1/2 in dogs and rats averaged 1.2 and 4.5 hr. Absolute oral bioavailability of CI-966 was 100% in both species. Following oral dosing of [14C]CI-966 HCl to dogs, fecal, and urinary excretion accounted for 89% and 2.3% of the 14C dose, respectively. In bile-duct cannulated rats, biliary excretion is the major elimination pathway of radioactivity (75%). Urinary and fecal excretion accounted for 4.1 and 12%, respectively. CI-966 does not induce or inhibit mouse hepatic mixed function oxidases, as determined by hexobarbital sleeping time.


Phosphoinositide-dependent protein kinase 1, a sensor of protein conformation.
Phosphoinositide-dependent protein kinase 1 (PDK1) is a protein kinase that phosphorylates and activates several other protein kinases from the AGC group (which includes PKA, PKG and PKC), to which PDK1 also belongs. Recent data suggests that PDK1 specificity is achieved by regulation of its interaction with substrates and supports a rather simple model explaining how PDK1 interacts with different substrates. The data further suggests that PDK1 interacts with its substrates when they are in a particular conformation (inactive). PDK1 has the ability to recognize, interact with and phosphorylate specific substrate conformations and thus sets PDK1 at the centre of a protein conformation sensor mechanism. The PDK1-substrate interaction model describes, at a molecular level, the mechanism used by PDK1 to sense the conformation of its substrates.


Pulmonary metastasectomy: analysis of survival and prognostic factors in 243 patients.
Pulmonary metastases are a sign of advanced malignant disease. Interdisciplinary management of metastatic cancer mandates the consideration of all treatment options, and in selected patients pulmonary metastasectomy can be performed with curative intent. This study aims to analyze the prognostic factors associated with survival and optimize the selection of surgical candidates. The sarcoma subset analysis aims to examine the role of multiple repeat resections for pulmonary metastatic recurrence. A total of 243 patients were analyzed in this retrospective cohort study. Overall survival was estimated using Kaplan-Meier analysis. Univariate analyses with log-rank tests and multivariate analysis with Cox proportional hazards model were undertaken to determine the independent prognostic factors for survival. Multivariate analyses identified germ cell cancer (P = 0.01) and a disease-free interval of >36 months (P = 0.006) as significant independent prognostic factors for improved survival, whilst synchronous metastases (P = 0.04), multiple metastases (P = 0.005) and incomplete resection (P < 0.001) were identified as significantly poor prognostic factors. Subset analyses identified that ≥2 repeat resections within the sarcoma cohort was associated with an increased median survival of 63.5 months (P = 0.04). In selected patients, pulmonary metastasectomy can be performed with curative intent and have associated long-term survival benefits. Patients presenting with recurrent sarcoma pulmonary metastases should be considered for repeat metastasectomy.


Impact of Discards for Living Donor Kidney Transplantation in a Transplant Program.
Living donor kidney transplantation (LDKT) is the best treatment for end-stage renal disease. In this setting, a significant percentage of transplants are not undertaken because of medical and nonmedical reasons of both donors and recipients. However, the impact of these discards in a transplant program has not been identified thoroughly so far. Our objective was to clarify key reasons for exclusion of LDKTs and the consequences for the discarded transplant candidates in the following 5 years. Analysis of donors' and recipients' characteristics of 781 couples evaluated in our hospital from January 2005 to December 2013. The consequences of discards in transplant candidates were analyzed in the cohort 2012 to 2013 (n = 106) and followed up until October 2018. In our study group, 402 (51.5%) LDKT couples were successfully donated, and 379 (48.5%) were excluded. Donor and transplant recipient candidates discarded were older at the evaluation (55.07 ± 12.14 years vs 51.73 ± 10.93 years, P < .001; 48.81 ± 14.05 years vs 44.62 ± 13.91 years, P < .001, respectively). The most frequent reason for kidney discard was medical contraindication found in the potential donor (47.5%; low eGFR, diabetes mellitus, impaired glucose tolerance, high blood pressure, cardiovascular pathology casually found during evaluation, and proteinuria). Of the discarded candidates from 2012 to 2013, 36.8% received a deceased donor kidney transplant, 17% a LDKT with another donor, 7.5% stayed on the waiting list, 18.9% died, 3.8% were excluded from the waiting list, and 14.2% were lost to follow-up. In most cases, transplantation was not undertaken because of donor pathology. Fifty-three percent of the discarded patients were eventually transplanted, with a 31.4% probability to receive an organ from another living donor.


Severe acute pancreatitis with abscess after extracorporeal shock wave lithotripsy: a rare complication.
Extracorporeal shock wave lithotripsy (ESWL) is a widely accepted procedure for urolithiasis. However, the shock waves do not pass through the body without damage. Here, we reported a 57-year-old man who underwent ESWL four times before, and immediately developed acute pancreatitis and peritoneal abscess after ESWL for a right renal stone. Although the possibility of post-ESWL acute pancreatitis is extremely low, urologists must be aware of this vital complication.


Frequency, tidal volume, and mean airway pressure combinations that provide adequate gas exchange and low alveolar pressure during high frequency oscillatory ventilation in rabbits.
We studied healthy and saline lavaged rabbits during high frequency oscillatory ventilation to determine what combination of frequency (f), tidal volume (Vt), and mean airway pressure (Paw) produced the lowest peak-to-peak alveolar pressure amplitude (Palv) and physiologic blood gas tensions. Sinusoidal volume changes were delivered through a tracheostomy by a piston pump driven by a linear motor. Tracheal pressure amplitude (Ptr) was measured through a tracheal catheter and alveolar pressure amplitude was measured in a capsule glued to the right lower lobe. PaO2, PaCO2, Ptr, and Palv were measured at the following settings: FiO2 = 0.5, frequency 2-28 Hz, Vt 1-3 mL/kg (50 150% dead space) and Paw 5-15 cm H2O. Many combinations of frequency and Vt resulted in the same PaO2 and PaCO2. Paw had a large effect on Palv and minimal effect on blood gas tensions. In lavaged rabbits, the composite variable f x Vt2 described the trends in Palv and blood gas tensions. As the product of f x Vt2 increased, PaO2 initially increased and then decreased, whereas PaCO2 decreased and Palv increased. No single combination of frequency, Vt and Paw simultaneously provided the lowest Palv and physiologic blood gas tensions. Adequate blood gas tensions and low Palv were obtained at frequencies less than 12 Hz, a Vt of 2 mL/kg and a Paw of 10 cm H2O. In healthy and lavaged rabbits PaO2 increased and PaCO2 decreased as frequency increased at lower Vt.PaO2 decreased as frequency increased at higher Vt in lavaged rabbits only. Palv tended to be greater in lavaged rabbits.


Localization of Rho GTPase in sea urchin eggs.
We isolated the urho1 (urchin rho in English or uni rho in Japanese) gene from the sea urchin cDNA library which encodes a Rho GTPase. Anti-URho1 antibodies specifically recognized a 22 kDa protein in the extracts of echinoderm eggs. URho1 was concentrated in the cortices from both unfertilized and fertilized eggs as judged by immunoblot analysis. URho1 may bind directly to the cell membrane but not be a component of the cortical layer. Immunofluorescence microscopy revealed that URho1 is localized to the cleavage furrow and the midbody during cytokinesis.


Waiting list for kidney transplants.
Medical and technological progress have made kidney transplants an effective, alternative therapy to dialysis for patients suffering from chronic kidney failure. Transplantation improves the quality of life of these patients significantly; however, waiting lists are long and this is because of the attitude of the general public to organ donation, not a lack of medical expertise. In fact, the only limiting factor in kidney transplant is the opposition to donation expressed by the deceased or family members. Herein we outline the distribution of patients on the kidney transplant waiting list in the Regional Transplant Centre for Abruzzo and Molise in L'Aquila, Italy, and highlight the reasons why patients are withdrawn from the list, the main reason being a deterioration in patient condition after long periods of dialysis.


Dependence of CO2 gas exchange and acid metabolism of the alpine CAM plant Sempervivum montanum on temperature and light.
The influence of light intensity and temperature on the diurnal course and magnitude of CO2 gas exchange and on acid metabolism was studied in the laboratory with rooted rosettes of Sempervivum montanum collected at 2,200 m above sea level in the Central Alps. Under a temperature regime having a cool dark period and warm light period, S. montanum exhibited the time course of CO2 gas exchange typical of a CAM plant; the response was very distinct even when the plants were well-watered. At day temperatures of less than 10° C and at night temperatures greater than 35° C, S. montanum behaved like a C3 plant. Characteristic for S. montanum are a broad temperature optimum and a wide range of temperatures in which CO2 uptake in light is possible (-2° to 45° C). Dark fixation of CO2 is evident between-2° and 35° C, an apparent uptake of external CO2, on the other hand, only as high as 20° C. Light saturation of CO2 uptake is reached at 60-80 W m-2 while the rate of deacidification is nearly maximal at 40 W m-2. These results show that, due to their specific metabolism, CAM plants can be favored not only in xeric habitats, but also in heat stressed mountain habitats where the daily variation in temperature may be extreme.


Cystic Adenoid Carcinoma: A Rare Bronchial Tumor.
Although very rare, cystic adenoid carcinoma (CAC) should be considered as a differential diagnosis for any lung tumor arising from the bronchial glands. The diagnosis is typically confirmed through histological examination, and treatment is primarily based on surgical intervention. In this report, we present the case of an 82-year-old male with primary CAC of the lung.


Regulation of cytokine-stimulated vascular cell adhesion molecule-1 expression in renal tubular epithelial cells.
Vascular cell adhesion molecule-1 (VCAM-1) is expressed not only by cytokine-activated endothelium in the kidney, but also by nonvascular cells such as renal tubular epithelial cells (TEC) and mesangial cells (MC). VCAM-1 is upregulated in these cells by the cytokines TNF-alpha, IL-1, and IFN-gamma. We have examined herein the regulation of VCAM-1 expression in TEC and the role played by protein kinase C (PKC). Activation of PKC with phorbol myristate acetate (PMA) or mezerein upregulates VCAM-1 expression by TEC dose-dependently. Maximal stimulation occurs after 6 hr, and declines thereafter. Activation of the protein kinase A pathway with forskolin does not upregulate VCAM-1. The TNF-alpha- and PMA-stimulated VCAM-1 expression is inhibited by the PKC and PKA inhibitor staurosporine (STS). The TNF-alpha-stimulated VCAM-1 expression is also inhibited by the PKC-specific inhibitor calphostin C. Protein synthesis inhibition with cycloheximide (CHX) and blocking of transcription with actinomycin D (ACT D) also inhibits the TNF-alpha and PMA-stimulated upregulation of VCAM-1. The TNF-alpha induced increase in VCAM-1 mRNA levels is blocked with STS and ACT D, but is superinduced with CHX. Thus, the TNF-alpha stimulated renal tubular VCAM-1 expression may involve activation of PKC and is transcriptionally regulated.


18F-5-Fluorouridine, a new probe for measuring the proliferation of tissue in vivo.
(1) Increased metabolic trapping of labeled fluorouridine reflects the interaction of three parameters in rapidly proliferating tissues: increased rates of intracellular phosphorylation, increased rates of transport, and increased rates of synthesis of RNA. (2) We have taken advantage of these metabolic phenomena, demonstrating in this paper that the uptake of 18F-5-fluorouridine, a positron-emitting radiopharmaceutical, can provide a very practical means for measuring changes in proliferative states of tissues in vivo. (3) Two major changes in proliferative states have been examined: one involves changes in growth of normal mouse tissues induced by pharmacological agents; the other involves tumor growth and neoplastic infiltration in mice and rabbits. (4) We describe tracer experiments with 18F-5-fluorouridylate, prepared by enzymatic means, and with 18F-5-fluorouridine, prepared by both enzymatic means and direct radiochemical procedures. (5) Uptakes of 18F after a pulse of 18F-5-fluorouridine were increased in mouse spleen following phenylhydrazine treatment to induce increased splenic erythropoiesis. (6) Uptakes of 18F in various mouse tissues were decreased following pretreatment with actinomycin D. This finding is consistent with the known inhibitory action of actinomycin on RNA synthesis. (7) Intracerebral Zimmerman ependymoblastoma tumors showed extraordinarily high uptakes of fluorine-18 in mice injected intravenously with 18F-5-fluorouridylate or with 18F-5-fluorouridine in contrast to very low uptakes by normal brain tissue. (8) After intracerebral injection of mice with suspensions of L1210 leukemia cells, distant organs such as lung, liver, and spleen became involved. These tissues showed significant increases of radioactivity after pulse labeling with 18F-5-fluorouridylate consistent with histological evidence for infiltration of these tissues by neoplastic cells. (9) Intramuscular VX2 carcinoma tumors in rabbits showed localized uptakes of 18F significantly higher than surrounding normal muscle tissue. (10) The most important clinical implication of the present work is the promise that 18F-5-fluorouridine uptakes can be followed in humans by positron emission tomography. This would provide a direct means of measuring different rates of in vivo proliferation in neoplasms, hematologic tissues and other organs undergoing rapid growth changes.


Repeat or single-dose lentiviral vector administration to mouse lungs? It's all about the timing.
Lentiviral vectors are attractive delivery vehicles for cystic fibrosis gene therapy owing to their low immunogenicity and ability to integrate into the host cell genome, thereby producing long-term, stable gene expression. Nonetheless, repeat dosing may be required to increase initial expression levels, and/or boost levels when they wane. The primary aim of this study was to determine if repeat dosing of a VSV-G pseudotyped LV vector delivered into mouse lungs is more effective than a single dose. C57Bl/6 mouse lungs were conditioned with lysophosphatidylcholine, followed one-hour later by a LV vector carrying the luciferase reporter gene, using six different short-term (≤1 wk) and long-term (>1 wk) dosing schedules. Luciferase expression was quantified using bioluminescence imaging over 12 months. Most dosing schedules produced detectable bioluminescence over the 12-month period, but the shorter intervals (≤1 wk) produced higher levels of flux than the longest interval (five doses at least 1-month apart). Ex vivo lung analysis at 12 months showed that the estimated mean flux for the group that received two doses 1-week apart was significantly greater than the single dose group and the two groups that received doses over a period greater than 1-week. These results suggest that early consecutive multiple doses are more effective at improving gene expression in mouse lungs at 12 months, than longer repeat dosing intervals.


Probiotic Lactobacillus reuteri promotes TNF-induced apoptosis in human myeloid leukemia-derived cells by modulation of NF-kappaB and MAPK signalling.
The molecular mechanisms of pro-apoptotic effects of human-derived Lactobacillus reuteri ATCC PTA 6475 were investigated in this study. L. reuteri secretes factors that potentiate apoptosis in myeloid leukemia-derived cells induced by tumour necrosis factor (TNF), as indicated by intracellular esterase activity, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling assays and poly (ADP-ribose) polymerase cleavage. L. reuteri downregulated nuclear factor-kappaB (NF-kappaB)-dependent gene products that mediate cell proliferation (Cox-2, cyclin D1) and cell survival (Bcl-2, Bcl-xL). L. reuteri suppressed TNF-induced NF-kappaB activation, including NF-kappaB-dependent reporter gene expression in a dose-and time-dependent manner. L. reuteri stabilized degradation of IkappaBalpha and inhibited nuclear translocation of p65 (RelA). Although phosphorylation of IkappaBalpha was not affected, subsequent polyubiquitination necessary for regulated IkappaBalpha degradation was abrogated by L. reuteri. In addition, L. reuteri promoted apoptosis by enhancing mitogen-activated protein kinase (MAPK) activities including c-Jun N-terminal kinase and p38 MAPK. In contrast, L. reuteri suppressed extracellular signal-regulated kinases 1/2 in TNF-activated myeloid cells. L. reuteri may regulate cell proliferation by promoting apoptosis of activated immune cells via inhibition of IkappaBalpha ubiquitination and enhancing pro-apoptotic MAPK signalling. An improved understanding of L. reuteri-mediated effects on apoptotic signalling pathways may facilitate development of future probiotics-based regimens for prevention of colorectal cancer and inflammatory bowel disease.


First-derivative UV spectrophotometric and high-performance liquid chromatographic analysis of some thiazide diuretics in the presence of their photodecomposition products.
Ethanolic solutions of three thiazide diuretics, chlorothiazide, hydrochlorothiazide and trichlormethiazide, were irradiated with a high-pressure mercury lamp. The products were isolated and their first-derivative UV spectra in ethanol were recorded and compared to those of the parent compounds. The determination of the parent compounds in the presence of the decomposition products was carried out at wavelengths near 220 nm using the zero-crossing technique. Three reversed-phase HPLC methods were also developed for the analysis of the parent compounds. In parallel analyses of the reaction mixtures a good correlation was achieved between these two methods in the determination of hydrochlorothiazide and trichlormethiazide while there was greater variation in the results of chlorothiazide.


Assessment of Lung Eosinophils In Situ Using Immunohistological Staining.
Eosinophils are rare white blood cells that are recruited from circulation to accumulate in the lung in mouse models of allergic respiratory inflammation. In hematoxylin-eosin (HE) stained lungs, eosinophils may be difficult to detect despite their bright eosin staining in the secondary granules. For this reason, antibody-mediated detection of eosinophils is preferable for specific and clearer identification of these cells. Moreover, eosinophils may degranulate, releasing their granule proteins into surrounding tissue, and remnants of cytolysed cells cannot be detected by HE staining. The methods here demonstrate the use of eosinophil-specific anti-mouse antibodies to detect eosinophil granule proteins in formalin-fixed cells both in situ in paraffin-embedded lungs, as well as in cytospin preparations from the lung. These antibody staining techniques enable either colorimetric or fluorescence imaging of eosinophils or their granule proteins with the potential for additional antibodies to be added for detection of multiple molecules.


Relation between the location of elements in the periodic table and various organ-uptake rates.
Fifty four elements and 65 radioactive compounds were examined to determine the organ uptake rates for rats 3, 24 and 48 h after i.v. injection of these compounds. They were prepared as carrier free nuclides, or containing a small amount of stable nuclide. Generally speaking, behaviors of K, Rb, Cs and Tl in all the organs were very similar to one another, but they differed from that of Na. Bivalent hard acids were avidly taken up into bone; therefore, uptake rates in soft tissues were very small. Hard acids of tri-, quadri- and pentavalence which were taken up into the soft tissue organs decreased more slowly from these organs than other ions. Soft acids such as Hg2+ were bound very firmly to the component in the kidney. Anions (with few exceptions), GeCl4 and SbCl3 were rapidly excreted in urine, so that the uptake rates in organs were low.


Gynecomastia demonstrated on the bone scan.
Bone scans with 99mtechnetium diphosphonate were performed on 2 patients with gynecomastia induced by diethylstilbestrol therapy for adenocarcinoma of the prostate. Neither patient had evidence of bone metastases but both scans revealed increased isotope concentration over the anterior rib cage at the lateral margin of the chest wall, corresponding in location to the hypertrophic breasts. This observation may be related to similar radionuclide uptake in normal and abnormal female breasts. One should not mistake the finding of gynecomastia for metastases of the ribs.


1-Hy-droxy-4-methyl-pyridinium chloride.
The title salt, C6H8NO+·Cl-, contains two cations and two anions in the asymmetric unit. The components are linked by O-H⋯Cl and C-H⋯Cl hydrogen bonds, leading to tetra- (square-planar) or penta-coordinated (square-pyramidal) chloride ions. The title salt is isostructural with its bromide analogue.


Ultraviolet metasurface-assisted photoacoustic microscopy with great enhancement in DOF for fast histology imaging.
Pathology interpretations of tissue rely on the gold standard of histology imaging, potentially hampering timely access to critical information for diagnosis and management of neoplasms because of tedious sample preparations. Slide-free capture of cell nuclei in unprocessed specimens without staining is preferable; however, inevitable irregular surfaces in fresh tissues results in limitations. An ultraviolet metasurface with the ability to generate an ultraviolet optical focus maintaining < 1.1-µm in lateral resolution and ∼290 µm in depth of field (DOF) is proposed for fast, high resolution, label-free photoacoustic histological imaging of unprocessed tissues with uneven surfaces. Microanatomical characteristics of the cell nuclei can be observed, as demonstrated by the mouse brain samples that were cut by hand and a ∼3 × 3-mm2 field of view was imaged in ∼27 min. Therefore, ultraviolet metasurface-assisted photoacoustic microscopy is anticipated to benefit intraoperative pathological assessments and basic scientific research by alleviating laborious tissue preparations.


Genome-wide methylation sequencing identifies progression-related epigenetic drivers in myelodysplastic syndromes.
The potential mechanism of myelodysplastic syndromes (MDS) progressing to acute myeloid leukemia (AML) remains poorly elucidated. It has been proved that epigenetic alterations play crucial roles in the pathogenesis of cancer progression including MDS. However, fewer studies explored the whole-genome methylation alterations during MDS progression. Reduced representation bisulfite sequencing was conducted in four paired MDS/secondary AML (MDS/sAML) patients and intended to explore the underlying methylation-associated epigenetic drivers in MDS progression. In four paired MDS/sAML patients, cases at sAML stage exhibited significantly increased methylation level as compared with the matched MDS stage. A total of 1090 differentially methylated fragments (DMFs) (441 hypermethylated and 649 hypomethylated) were identified involving in MDS pathogenesis, whereas 103 DMFs (96 hypermethylated and 7 hypomethylated) were involved in MDS progression. Targeted bisulfite sequencing further identified that aberrant GFRA1, IRX1, NPY, and ZNF300 methylation were frequent events in an additional group of de novo MDS and AML patients, of which only ZNF300 methylation was associated with ZNF300 expression. Subsequently, ZNF300 hypermethylation in larger cohorts of de novo MDS and AML patients was confirmed by real-time quantitative methylation-specific PCR. It was illustrated that ZNF300 methylation could act as a potential biomarker for the diagnosis and prognosis in MDS and AML patients. Functional experiments demonstrated the anti-proliferative and pro-apoptotic role of ZNF300 overexpression in MDS-derived AML cell-line SKM-1. Collectively, genome-wide DNA hypermethylation were frequent events during MDS progression. Among these changes, ZNF300 methylation, a regulator of ZNF300 expression, acted as an epigenetic driver in MDS progression. These findings provided a theoretical basis for the usage of demethylation drugs in MDS patients against disease progression.


Application of near-infrared hyperspectral (NIR) images combined with multivariate image analysis in the differentiation of two mycotoxicogenic Fusarium species associated with maize.
Maize (Zea mays L.) is one of the most versatile crops worldwide with high socioeconomic relevance. However, mycotoxins produced by pathogenic fungi are of constant concern in maize production, as they pose serious risks to human and animal health. Thus, the search for rapid detection and/or identification methods for mycotoxins and mycotoxin-producing fungi for application in food safety remain important. In this work, we implemented use of near infrared hyperspectral images (HSI-NIR) combined with pattern recognition analysis, partial-least-squares discriminant analysis (PLS-DA) of images, to develop a rapid method for identification of Fusarium verticillioides and F. graminearum. Validation of the HSI-NIR method and subsequent analysis was realized using 15 Fusarium spp. isolates. The method was efficient as a rapid, non-invasive, and non-destructive assessment was achieved with 100% accuracy, sensitivity, and specificity for both fungi.


Negative findings on fine-needle aspiration biopsy of solid breast masses: patient management.
A series of 245 fine-needle aspirations of solid breast masses has been reviewed. Seven aspirations were reported as unsatisfactory, 178 revealed benign masses, 7 were indeterminate, and 53 revealed malignancy. Fifty-two of 53 masses diagnosed on aspiration as malignant were confirmed by surgical biopsy (98 percent sensitivity). Open biopsy was carried out on 50 of 178 masses reported as negative on needle biopsy and benign masses were revealed in 46 cases (92 percent specificity). The remaining 128 masses with negative findings were observed and follow-up of 101 patients obtained. Cancer did not develop in any of these patients. Careful physical examination and mammography can predict if a breast mass is malignant or benign in 85 to 90 percent of patients. If fine-needle aspiration biopsy is added and performed by physicians and cytopathologists experienced in the technique, additional information is obtained which allows greater diagnostic accuracy and may eliminate many breast biopsies.


Characterization and antioxidant properties of chitosan film incorporated with modified silica nanoparticles as an active food packaging.
In this study, two modified silica nanoparticles (SiO2-GA NPs) were successfully obtained by covalently grafting gallic acid onto silica nanoparticles. The mean particle diameters of their were 112.7 ± 0.55 nm (1-SiO2-GA NPs) and 408.7 ± 3.20 nm (4-SiO2-GA NPs), respectively. Novel antioxidant active packaging composite films were prepared by incorporation of 1-SiO2-GA NPs or 4-SiO2-GA NPs into chitosan. The structure analysis of the composite films showed that intermolecular hydrogen bonds were formed between the two modified silica nanoparticles and chitosan. Compared with the chitosan film, the mechanical properties, water vapor barrier property and UV light barrier ability of the composite films were significantly improved. Moreover, the incorporated of the two modified silica nanoparticles significantly increased antioxidant activity of the composite films. This study indicates that composite films incorporated with modified silica nanoparticles, especially the incorporation of 1-SiO2-GA NPs can be used as novel antioxidant food packaging composite films.


Effect of wavelength on cutaneous pigment using pulsed irradiation.
Several reports have been published over the last two decades describing the successful removal of benign cutaneous pigmented lesions such as lentigines, café au lait macules' nevi, nevus of Ota, and lentigo maligna by a variety of lasers such as the excimer (351 nm), argon (488,514 nm), ruby (694 nm), Nd:YAG (1060 nm), and CO2 (10,600 nm). Laser treatment has been applied to lesions with a range of pigment depths from superficial lentigines in the epidermis to the nevus of Ota in the reticular dermis. Widely divergent laser parameters of wavelength, pulse duration, energy density, and spotsizes have been used, but the laser parameters used to treat this range of lesions have been arbitrary, with little effort focused on defining optimal laser parameters for removal of each type. In this study, miniature black pig skin was exposed to five wavelengths (504, 590, 694, 720, and 750 nm) covering the absorption spectrum of melanin. At each wavelength, a range of energy densities was examined. Skin biopsies taken from laser-exposed sites were examined histologically in an attempt to establish whether optimal laser parameters exist for destroying pigment cells in skin. Of the five wavelengths examined, 504 nm produced the most pigment specific injury; this specificity being maintained even at the highest energy density of 7.0 J/cm2. Thus, for the destruction of melanin-containing cells in the epidermal compartment, 504 nm wavelength appears optimal.


Development of an innovative decentralized treatment system for the reclamation and reuse of strong wastewater from rural community: Effects of elevated CO2 concentrations.
In a previous study, a soil-plant-based natural treatment system was successfully developed for post-treatment of anaerobically digested strong wastewater full of potential nutrients (nitrogen, phosphorus, and potassium). For upgraded performance, an innovative decentralized treatment system was further developed, in which an anaerobic digestion stage and a natural treatment system stage are placed within a greenhouse. This allows the CO2 generated by the processing of wastewater and biogas consumption to be sequestrated within the greenhouse for elevating its concentration level and potentially enhance nutrient removal and recovery from the applied wastewater. To investigate the feasibility of the system, a bench-scale experiment was conducted using CO2 chambers. Valuable Kentucky bluegrass was planted in two soil types (red ball earth and black soil) at three CO2 concentrations (340 ppm, 900 ppm, and 1400 ppm). The results confirmed the positive effects of elevated CO2 concentration on the biomass production and turf quality of Kentucky bluegrass as well as the resulting higher nutrient recovery efficiencies. More importantly, it was demonstrated that the elevated CO2 concentration significantly stimulated the soil nitrifying microorganisms and thus improved the nitrogen removal efficiency (a critical issue in ecological wastewater treatment). A CO2 concentration of 1400 ppm is therefore recommended for use in the system. The mechanism underlying this phenomenon was shown to be an indirect effect, in which the higher CO2 concentration first positively influenced growing plants, which then stimulated the soil nitrifier communities. The effects of soil type (a design parameter) and hydraulic and nutrient loading rates (an operational parameter) on system performance were also examined. The results favored black soil for system establishment. Based on the findings of this study, our proposed system is thought to have the potential to be scaled up and adopted by rural communities worldwide for the reclamation and reuse of strong wastewater, addressing the agricultural non-point source pollution, and achieving the sustainable development.


Hydrostatic reduction of ileocolic intussusception: a second attempt in the operating room with general anesthesia.
Over a 3-year-period, standard treatment with hydrostatic pressure from a contrast enema failed to reduce ileocolic intussusception in 31 of 62 children. With the child anesthetized in the operating room, a second contrast enema was given before laparotomy. Of the 31 intussusceptions, 21 (68%) were reduced without complication, thereby avoiding the discomfort, longer hospitalization, complications, and expense of surgery. Nine of the remaining 10 intussusceptions were difficult to reduce manually during surgery or required resection. The overall nonoperative reduction rate for the 3-year period was 84%; for the last 2 years it was 90%. Success with the second enema may be related to the effects of general anesthesia. In addition, partial reduction with the first enema may improve blood flow from the intussusceptum so that it becomes smaller and easier to reduce with the second enema. Because it can easily be added to standard management protocols without increased risk, routine use of this second enema with anesthesia is recommended.


Epithelial cell proliferation and apoptosis in the developing murine palatal rugae.
Epithelial cell proliferation and apoptosis during morphogenesis of the murine palatal rugae (PR) were examined histochemically by using anti-bromodeoxyuridine (BrdU) and the terminal deoxynucleotidyl transferase-mediated UTP nick-end-labelling (TUNEL) technique. Formation of the PR rudiment was observed as an epithelial placode in fetuses at 12.5 days post-coitus (dpc). During the PR formation, BrdU-positive cells were detected mainly in the epithelium of the interplacode and interprotruding areas in fetuses administered BrdU maternally at 2 h before killing. TUNEL-positive cells were detected only at the epithelial placode area in 12.5-14.5 dpc. At 16.5-18.5 dpc, the BrdU-positive cells were decreased in number in the epithelial cells at the interprotruding area of the PR. Only a few TUNEL-positive cells were observed in the protruding area of the PR at 16.5 dpc. These results suggest that cell proliferation and apoptosis in the palatal epithelium are involved spatiotemporally in the murine PR morphogenesis.


[Changes in brain memory functions as affected by a constant magnetic field].
Effects of CMF on memory processes in adult volunteers (non-sleep us hypnotic condition) has been studied at laboratory and clinical conditions. The results point out that CMF changes the interhemispheric relations and result in memory malfunction. The malfunction of memory activity in volunteers after action of CMF was influenced by two factors: magnetic field position under different brain areas and functional status of volunteers: awake or hypnotic.


Treatment of life-threatening ventricular arrhythmias by a combination of antiarrhythmic drugs and right ventricular pacing.
Thirteen patients with intractable ventricular arrhythmias were studied; they underwent long-term treatment by a combination of antiarrhythmic drugs and ventricular pacing. Eleven patients had a history of tachycardia and two had torsade de pointes; eleven of thirteen had had cardioversion and/or defibrillation. Prior to permanent pacemaker implantation, temporary pacing in the VVI mode was used in combination with one or more of the following drugs: amiodarone, aprindine, digitalis, metoprolol, mexiletine, procainamide, pindolol, propranolol, or quinidine. Various pacing rates were tried; when permanent pacing was instituted, a unipolar system which was at least rate-programmable was used. Right ventricular VVI pacing, combined with drug therapy, was successful in ten of thirteen patients. Five of the ten patients are alive and free of arrhythmias after 78, 72, 72, 54, and 11 months, respectively. Although five patients died (after 60, 48, 30, 24, and 9 months, respectively), none of the deaths were related to arrhythmias. We suggest that in patients with ventricular arrhythmias refractory to conventional treatment, a therapeutic trial of right ventricular VVI pacing in combination with a drug regimen be used.


Biobased and compostable trilayer thermoplastic films based on poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and thermoplastic starch (TPS).
Food preservation is crucial in safeguarding the global food supply and security. Current regulations do not encourage the use of chemical food preservatives. Therefore, creating a physical barrier in the form of packaging remains a necessary measure to prevent food contact with biological and physical contaminants. This work presents a novel biodegradable thin trilayer assembly of two sandwiching layers of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), and a core layer composed of thermoplastic starch (TPS), maleated TPS, or their blends with PHBV (80/20). Scanning electron microscope (SEM), and optical microscopy images showed the samples' consistent film formation. The tensile test revealed that the sample with a core layer of a blend of maleated TPS and PHBV was the strongest, with a modulus of 178 MPa. The water vapor transmission rates were as low as 20.2 g/(m2·d). The oxygen permeation rate was below the detection limit of the test. Most importantly, the samples pass the biodegradation (28 °C) disintegration test in less than six weeks. The study confirmed that a trilayer structure with two outer layers of PHBV, and a middle layer of TPS-PHBV blend provides excellent barrier properties in conjuncture with its biodegradability making it an appealing, sustainable food packaging material option.


Hly176B, a low-salt tolerant halolysin from the haloarchaeon Haloarchaeobius sp. FL176.
Extracellular proteases of haloarchaea can adapt to high concentrations of NaCl and can find useful applications in industrial or biotechnology processes where hypersaline conditions are desired. The diversity of extracellular proteases produced by haloarchaea is largely unknown though the genomes of many species have been sequenced and are publicly available. In this study, a gene encoding the extracellular protease Hly176B from the haloarchaeon Haloarchaeobius sp. FL176 was cloned and expressed in Escherichia coli. A related gene homolog to hly176B, hly176A, from the same strain was also expressed in E.coli, but did not show any proteinase activity after the same renaturation process. Therefore, we focus on the enzymatic properties of the Hly176B. The catalytic triad Asp-His-Ser was confirmed via site-directed mutagenesis, indicating that Hly176B belongs to the class of serine proteases (halolysin). Unlike previously reported extracellular proteases from haloarchaea, the Hly176B remained active for a relatively long time in an almost salt-free solution. In addition, the Hly176B displayed prominent tolerance to some metal ions, surfactants and organic solvents, and exerts its highest enzyme activity at 40 °C, pH 8.0 and 0.5 M NaCl. Therefore, this study enriches our knowledge of extracellular proteases and expands their applications for various industrial uses.


Alpha-conotoxin Vc1.1 alleviates neuropathic pain and accelerates functional recovery of injured neurones.
This paper demonstrates the capacity of the neuronal nicotinic acetylcholine receptor (nAChR) antagonist alpha-conotoxin Vc1.1 to inhibit pain responses in vivo. Vc1.1 suppressed pain behaviors when tested in two models of peripheral neuropathy of the rat sciatic nerve, the chronic constriction injury (CCI) and partial nerve ligation (PNL) models. Mechanical hyperalgesia was assessed using an Ugo Basile Analgesymeter. Vc1.1 was administered by intramuscular bolus injection near the site of injury at doses of 0.036 microg, 0.36 microg and 3.6 microg in CCI rats and at a dose of 0.36 microg in PNL rats. Vc1.1 was also administered contralaterally in CCI rats at doses of 0.36 microg and 3.6 microg. Treatment started after the development of hyperalgesia and continued for 7 days. Vc1.1 significantly attenuated mechanical hyperalgesia in both CCI and PNL rats for up to a week following cessation of treatment. Vc1.1 also accelerated functional recovery of injured neurones. A blister was raised over the footpad innervated by the peripheral terminals of the injured nerve. The ability of these terminals to mount an inflammatory vascular response upon perfusion of the blister base with substance P provided a measure of functional recovery. This study shows that alpha-conotoxin Vc1.1, a neuronal nAChR antagonist, suppressed mechanical pain responses associated with peripheral neuropathy in rats in vivo and accelerated functional recovery of the injured neurones. A role for neuronal nAChRs in the analgesic activity of Vc1.1 is proposed.


Reverse sphingomyelin-synthase in rat liver chromatin.
The chromatin phospholipid fraction is enriched in sphingomyelin content which changes during cell maturation and proliferation. Recently, we have demonstrated that the sphingomyelin variations can be due to chromatin neutral sphingomyelinase and sphingomyelin-synthase activities which differ in pH and K(m) optima from those present in nuclear membranes. The sphingomyelin can be used also as a source of phosphorylcholine for phosphatidylcholine synthesis by reverse sphingomyelin-synthase. In the present work we have studied the possible existence of reverse sphingomyelin-synthase activity in nuclear membrane and chromatin. A very low activity was detected in the homogenate, cytosol and nuclear membrane (0.93+/-0.14, 2.61+/-0.33 and 0.87+/-0.13 pmol/mg protein/min, respectively), whereas the activity present in chromatin was 37.09+/-2.05 pmol/mg protein/min. The reverse sphingomyelin-synthase decreases the intranuclear diacylglycerol pool and increases the intranuclear ceramide pool, whereas sphingomyelin-synthase has an opposite effect. The possible correlation between these enzymes is discussed.


Influence of linseed oil on cholesterol-induced atherosclerosis in rabbits.
Four groups of rabbits were studied to determine the effect of linseed oil on cholesterol-induced atherosclerosis. Group C received cholesterol alone; group CL received cholesterol and linseed oil, group L were given linseed oil alone, while group N were fed the normal stock diet for 18 weeks. Cholesterolemia was marked in groups C and CL but not in groups L or N. Cholesterolemia was significantly greater (P less than 0.001) in group CL (462 mg/dl) than in group C (318.6 mg/dl). Thus, the addition of linseed oil to cholesterol led to greater hypercholesterolemia than with the cholesterol diet alone. There was no significant change in the serum triglyceride level in either group. Atherosclerotic lesions (mostly fatty streaks but some fibrous plaques) were present only in groups C and CL and were absent in groups L and N. The percentage of atherosclerotic intimal involvement was significantly greater in group CL than C (P less than 0.001). The severity of atherosclerosis correlated with serum cholesterol levels (r = 0.79, P less than 0.001), but not with serum triglyceride levels.


Aspects of Cardiometabolic Risk in Women with Polycystic Ovary Syndrome.
Women with polycystic ovary syndrome (PCOS), the most common endocrine disorder among women of reproductive age, exhibit an adverse cardiovascular risk profile characteristic of the cardiometabolic syndrome. These women, compared with age- and body mass index-matched women without PCOS, appear to present a higher risk of insulin resistance, glucose intolerance, and dyslipidemia, and possibly a higher rate of type 2 diabetes mellitus and cardiovascular disease. However, despite the presence of cardiovascular risk factors and increased surrogate markers of cardiovascular disease, it is unclear whether they have accelerated atherosclerosis and greater mortality, the latter mainly because of a lack of endpoint studies. This article addresses, summarizes, and discusses salient data from the existing literature, including gaps and uncertainties, aspects, and mechanisms related to the spectrum of adverse cardiometabolic profile factors in women with PCOS.


Fluctuating asymmetry and wing size of Argia tinctipennis Selys (Zygoptera: Coenagrionidae) in relation to riparian forest preservation status.
Effects of riparian vegetation removal on body size and wing fluctuating asymmetry (FA) of Argia tinctipennis Selys (Odonata: Coenagrionidae) were studied in the River Suiá-Miçú basin, which is part of the Xingu basin in Brazilian Amazonia. A total of 70 specimens (n = 33 from preserved and n = 37 from degraded areas) was measured. Five wing measures of each wing (totalizing ten measured characters) were taken. Preserved and degraded points presented non-overlapped variations of a Habitat Integrity Index, supporting the environmental differentiation between these two categories. FA increases in degraded areas approximately four times for the width between the nodus and proximal portion of the pterostigma of forewings (FW), two times for the width of the wing in the region of nodus of FW, and approximately 1.7 times for the number of postnodal cells of FW. The increase is almost five times for the width between the nodus and the proximal portion of the pterostigma of hind wings (HW), three times for the number of postnodal cells of HW, and approximately 1.6 times the width between quadrangle and nodus of HW. Individuals of preserved sites were nearly 3.3% larger than for degraded sites, based on mean hind wing length. Our results supports that the development of A. tinctipennis in degraded areas is affected by riparian vegetation removal and may reflect in wing FA variations. Consequently, these FA measures may be a useful tool for bioassessment using Odonata insects as a model.


Utility of intraoperative frozen section analysis of sentinel lymph nodes in breast cancer.
Intraoperative frozen section pathologic analysis of sentinel lymph node (SLN) may guide immediate (single-stage) completion axillary dissection for patients with nodal metastases. The results of 203 consecutive patients undergoing SLN biopsy who had intraoperative pathology consultation between January 1998 and September 2000 were reviewed. SLN were analyzed by standard frozen section procedures. Final pathologic analysis included hematoxylin and eosin (H&E) staining of serial sections at 2-mm intervals. Frozen section analysis correctly identified a positive or negative result in 185 of 203 cases (overall accuracy 91%). In 17 of 53 cases, the SLNs were negative for tumor by frozen section, but positive on permanent section analysis (sensitivity 68%). The mean size of the nodal metastases was 6.2 mm and 1.5 mm in patients found to have true positive and false negative results, respectively (P <0.003). A single false positive SLN is reported. Two thirds of the patients were spared the need for reoperative axillary lymphadenectomy.


Generation of RNA sequencing libraries for transcriptome analysis of globin-rich tissues of the domestic dog.
We have developed a protocol for barcoded cDNA libraries of 48 samples to study gene expression across tissues in the domestic dog, Canis familiaris, by modifying the Single-Cell Tagged Reverse Transcription (STRT) protocol (Islam et al., 2012, 2014). The cDNA reads represent mRNA 5' ends, enabling the study of transcription start sites (TSS). Our modifications include longer UMIs for molecular counting and Globin-Lock® to deplete globin mRNAs that are abundant in blood and blood-rich tissues dominating all reads.


Computational Studies in Drug Design Against Cancer.
The application of in silico tools in the development of anti cancer drugs. The summing of different computer aided drug design approaches that have been applied in the development of anti cancer drugs. Structure based, ligand based, hybrid protein-ligand pharmacophore methods, Homology modeling, molecular docking aids in different steps of drug discovery pipeline with considerable saving in time and expenditure. In silico tools also find applications in the domain of cancer drug development. Structure-based pharmacophore modeling aided in the identification of PUMA inhibitors, structure based approach with high throughput screening for the development of Bcl-2 inhibitors, to derive the most relevant protein-protein interactions, anti mitotic agents; I-Kappa-B Kinase β (IKK- β) inhibitor, screening of new class of aromatase inhibitors that can be important targets in cancer therapy. Application of computational methods in the design of anti cancer drugs was found to be effective.


The infant with possible biliary atresia: evaluation by ultrasound and nuclear medicine.
Twenty-eight infants with jaundice were evaluated with ultrasound and radionuclide scans. Comparison of these studies with pathologic, surgical and clinical examinations demonstrated good correlation between ultrasonic and radionuclide studies. Ultrasound is an important preliminary study in the workup of such patients. Combined imaging provides the most information in a patient with suspected biliary atresia.


Exploring behavioral adjustments of proportion congruency manipulations in an Eriksen flanker task with visual and auditory distractor modalities.
The present study investigated global behavioral adaptation effects to conflict arising from different distractor modalities. Three experiments were conducted using an Eriksen flanker paradigm with constant visual targets, but randomly varying auditory or visual distractors. In Experiment 1, the proportion of congruent to incongruent trials was varied for both distractor modalities, whereas in Experiments 2A and 2B, this proportion congruency (PC) manipulation was applied to trials with one distractor modality (inducer) to test potential behavioral transfer effects to trials with the other distractor modality (diagnostic). In all experiments, mean proportion congruency effects (PCEs) were present in trials with a PC manipulation, but there was no evidence of transfer to diagnostic trials in Experiments 2A and 2B. Distributional analyses (delta plots) provided further evidence for distractor modality-specific global behavioral adaptations by showing differences in the slope of delta plots with visual but not auditory distractors when increasing the ratio of congruent trials. Thus, it is suggested that distractor modalities constrain global behavioral adaptation effects due to the learning of modality-specific memory traces (e.g., distractor-target associations) and/or the modality-specific cognitive control processes (e.g., suppression of modality-specific distractor-based activation). Moreover, additional analyses revealed partial transfer of the congruency sequence effect across trials with different distractor modalities suggesting that distractor modality may differentially affect local and global behavioral adaptations.


Interface homogeneity of adhesively luted glass fiber posts.
The aim of this study was to light microscopically evaluate the homogeneity of the cement interface of an adhesively luted glass fiber post (GFP) by using a new cement application aid compared to a conventional post cementation method. Twenty artificial root canals (n = 5) received GFP under the following experimental conditions: I = RelyX Unicem applied with a new application aid, II = RelyX Unicem, III = Panavia F 2.0 and IV = Variolink II (groups II-IV with conventional post cementation). From all specimens standardized photographs were taken perpendicularly to the post surface under a light-optical microscope from two opposite sides. The depicted cement interfaces were analysed using surface-analyzing software and related to the complete three-dimensional surface of the cement interface. Non-parametric tests were used to compare median values of the observed inhomogeneities (alpha = 5%). The median values (%) of inhomogeneities within the cement interface for the cervical, middle, and apical level of analysis were: I = 2, 2, 7; II = 15, 19, 24; III = 8, 16, 39; IV = 11, 16, 29. For the complete post length, median values (%) of inhomogeneities were: I = 4; II = 19; III = 20; IV = 18. The conventional application technique for luting endodontic post results in a large number of voids and bubbles. The combination of a flexible root-canal-shaped application aid achieves a more homogenous cement interface for the self-adhesive luting material tested.


Fetal Anomalies Associated with Novel Pathogenic Variants in TMEM94.
Intellectual developmental disorder with cardiac defects and dysmorphic facies (IDDCDF, MIM 618316) is a newly described disorder. It is characterized by global developmental delay, intellectual disability and speech delay, congenital cardiac malformations, and dysmorphic facial features. Biallelic pathogenic variants of TMEM94 are associated with IDDCDF. In a prenatal setting, where fetal abnormalities were detected using antenatal sonography, we used trio-exome sequencing (trio-ES) in conjunction with chromosomal microarray analysis (CMA) to identify two novel homozygous loss of function variants in the TMEM94 gene (c.606dupG and c.2729-2A>G) in two unrelated Saudi Arabian families. This study provides confirmation that TMEM94 variants may cause IDDCDF. For the first time we describe the pathogenicity of TMEM94 defects detected during the prenatal period.


Changes in lipoprotein composition during the menstrual cycle.
Composition of major plasma lipoproteins was studied in 14 normal women during different phases of the menstrual cycle for three consecutive months. The results were compared to measurements in ten normal age-matched men for a comparable period, to delineate possible sex differences in lipoprotein metabolism in young adults. Blood samples were obtained every 3--5 days after a 14-hr overnight fast and processed for determinations of total plasma cholesterol, LDL- and HDL-cholesterol, and apoproteins B and A-1. In premenopausal women, a significant, 10%--25% cyclical suppression of total plasma cholesterol, LDL-Chol, and LDL-apoB occurred during the luteal phase, which was significantly lower than unchanging concentrations found in men at any time interval. HDL-Chol remained in a significantly higher fixed concentration range in the female subjects as compared to the men. These sex differences in lipoprotein metabolism may have relevance to the reduced susceptibility of premenopausal women to atherosclerosis.


Clinical usefulness of quantitative evaluation of visceral fat by ultrasonography.
The aim of this work was to evaluate the usefulness of a proposed method for visceral fat volume assessment by ultrasonography (US) in identifying those at risk of metabolic syndrome, and also to establish the most suitable cutoff level of waist circumference for the diagnosis of visceral adiposity. One hundred and fifty-two outpatients with metabolic diseases such as hypertension, diabetes, or dyslipidemia were studied. The total visceral fat volume (total-VFA) was measured by computed tomography (CT), the visceral fat area at the level of the umbilicus was measured by CT (CT-VFA), and the visceral fat area was also measured by US (US-VFA), as we recently proposed. Significant correlation coefficients were found between total-VFA and CT-VFA, US-VFA, and waist circumference in men but not in women. The correlation co-efficient between US-VFA and waist circumference was significantly positive in men and weakly positive in women. According to receiver-operator characteristic curves, the cutoff value of waist circumference yielding the maximal sensitivity plus specificity for predicting more than 100 cm(2) of US-VFA was 85 cm in men and 84 cm in women. The change in US-VFA was significantly larger than that in waist circumference after a 6-month interval. The US-measured visceral fat area is more useful than waist circumference in a clinical setting.