Comparison of LH-RH analogue 1-month depot and 3-month depot by their hormone levels and pharmacokinetic profile in patients with advanced prostate cancer.
In an open, randomized phase II pharmacokinetic study conducted in Germany and Italy, a total of 42 patients with advanced or metastatic prostate cancer (PCa) were treated for 9 months with the luteinizing hormone-releasing hormone analogue (LH-RH-a) leuprorelin acetate depot in two different formulations. Fifteen patients received the 1-month depot and 27 patients received the newly developed 3-month depot, containing 3.75 mg and 11.25 mg, respectively. In both groups, subcutaneous injections of leuprorelin acetate injected monthly or at 3-month intervals produced a complete down-regulation of the pituitary and led to persistent suppression of testosterone and dihydrotestosterone to the castrate range (< or = 50 ng/dl for testosterone) within the first month of treatment, which thereafter could be maintained over the entire observation period of 9 months. In 10 patients, pretreatment with an antiandrogen for the prevention of clinical flare-up resulted in a slightly more profound and earlier drop in serum testosterone. The 3-month depot showed a higher median peak serum concentration (Cmax) of leuprorelin at 20.8 ng/ml than the 1-month depot at 10.7 ng/ml but, conversely, this did not influence the rise in serum testosterone levels. Cmax occurred at 3 h for the 3-month and at 1 h for the 1-month depot formulation. During the steady state, constant release could be detected, starting on day 3 and day 7 for the 1-month and 3-month depot, respectively. A marked decrease in median prostate-specific antigen levels of 97.8% (1-month depot) and 96.6% (3-month depot) compared with baseline was observed, indicating an objective clinical response for more than 80% of all patients in both arms. Based on European Organization for Research and Treatment of Cancer criteria, the best response in terms of complete/partial remissions and stabilization was comparable in the two arms at 86.7% (1-month depot) and 85.2% (3-month depot). 6.7% in the 1-month group and 3% in the 3-month depot group showed progression of the disease. The most common side effects in both treatment groups were related to hormone deprivation. Both formulations of the potent LH-RH-a leuprorelin acetate were highly effective in the treatment of advanced PCa and led to comparable endocrine and clinical effects.


Stem cell-based therapies for tumors in the brain: are we there yet?
Advances in understanding adult stem cell biology have facilitated the development of novel cell-based therapies for cancer. Recent developments in conventional therapies (eg, tumor resection techniques, chemotherapy strategies, and radiation therapy) for treating both metastatic and primary tumors in the brain, particularly glioblastoma have not resulted in a marked increase in patient survival. Preclinical studies have shown that multiple stem cell types exhibit inherent tropism and migrate to the sites of malignancy. Recent studies have validated the feasibility potential of using engineered stem cells as therapeutic agents to target and eliminate malignant tumor cells in the brain. This review will discuss the recent progress in the therapeutic potential of stem cells for tumors in the brain and also provide perspectives for future preclinical studies and clinical translation.


A histochemical study of the distribution of dextran 500 in human corneas during organ culture.
The aim of this histochemical study was to demonstrate the absorption of dextran 500 and its distribution in the cornea after storage under standard eye bank conditions. Furthermore, an attempt was made to distinguish between the soluble and insoluble parts of dextran 500 absorbed by the cornea, in order to see how much dextran remains in the cornea after transplantation. Forty-nine fresh and 65 organ-cultured human corneas were investigated. The corneas were cultured for 28 days in a dextran-free medium, followed by a period of 1-14 days in a medium containing 5% dextran 500. Cryosections were stained by aqueous PAS and a modified alcoholic PAS to determine the amount of dextran. Dextran was not found in the epithelium, stroma or endothelium of fresh human corneas. By contrast, extra- and intracellular positive staining reactions were detected in corneas following storage in a medium containing dextran. Dextran 500 absorption was relatively diffuse in the epithelium after storage in a dextran medium. Initial accumulations were found in the stroma near Bowman's and Descemet's membranes and also in the central part of the cornea, as the period of culture in the medium containing dextran lengthened. We also observed interaction between the stroma and endothelium: decreasing amounts in the endothelium were followed by an increase of same in the stroma. Intracellular deposits of dextran were detected after only one day. A much greater part of the extracellular dextran than previously described was found to be insoluble. As the amount of dextran in the cornea increases over a longer storage time, we conclude that the period of storage in a medium containing dextran should be limited to four days. The fact that the cornea is saturated with dextran after seven days has been shown in further studies to interfere with mitochondrial function and may also cause severe post-operative swelling of the transplant, hence leading to a longer recovery period for the patient.


Adenosine release: a potential explanation for the benefits of ticagrelor in the PLATelet inhibition and clinical outcomes trial?
the objective of the study was to hypothesize on the potential mechanism explaining the surprising mortality benefit of ticagrelor in the PLATO trial. in PLATO, the mortality reduction (107 deaths) numerically exceeds the myocardial infarction prevention benefit (89 events), making it a hitherto unmatchable achievement of ticagrelor over active comparator. If confirmed, such an impressive mortality advantage will be critical for the further success of ticagrelor to compensate for its otherwise unfavorable safety profile. In fact, such an impressive survival represents an entirely unexpected benefit, which will serve as a key point in the drug approval process and subsequent use in clinical practice. The potential association of ticagrelor as a promoter of blood adenosine serving as adenosine agonist is assessed. multiple properties of adenosine, which can be closely matched with both clinical benefits and adverse events after ticagrelor, suggest that this novel pyrimidine is not a pure antiplatelet agent. Unquestionably, ticagrelor potently inhibits platelet activity via established mechanism of P2Y12 receptor blockade, probably chronically increasing blood adenosine levels and ultimately contributing to the vascular outcome benefit observed in PLATO. future randomized trials of ticagrelor in acute heart failure, sudden death prevention, and treatment of atrial fibrillation are warranted and will expand our understanding of the potential role of adenosine in the outcome benefit after pyrimidines.


Target SNP selection in complex disease association studies.
The massive amount of SNP data stored at public internet sites provides unprecedented access to human genetic variation. Selecting target SNP for disease-gene association studies is currently done more or less randomly as decision rules for the selection of functional relevant SNPs are not available. We implemented a computational pipeline that retrieves the genomic sequence of target genes, collects information about sequence variation and selects functional motifs containing SNPs. Motifs being considered are gene promoter, exon-intron structure, AU-rich mRNA elements, transcription factor binding motifs, cryptic and enhancer splice sites together with expression in target tissue. As a case study, 396 genes on chromosome 6p21 in the extended HLA region were selected that contributed nearly 20,000 SNPs. By computer annotation ~2,500 SNPs in functional motifs could be identified. Most of these SNPs are disrupting transcription factor binding sites but only those introducing new sites had a significant depressing effect on SNP allele frequency. Other decision rules concern position within motifs, the validity of SNP database entries, the unique occurrence in the genome and conserved sequence context in other mammalian genomes. Only 10% of all gene-based SNPs have sequence-predicted functional relevance making them a primary target for genotyping in association studies.


Contemporary Correction of Dentofacial Anomalies: A Clinical Assessment.
Contemporary computer-assisted technologies can support the surgical team in the treatment of patients affected by dentofacial deformities. Based on own experiences of 350 patients that received orthognathic surgery by the same team from 2007 to 2015, this clinical review is intended to give an overview of the results and risks related to the surgical correction of dentofacial anomalies. Different clinical and technological innovations that can contribute to improve the planning and transfer of corrective dentofacial surgery are discussed as well. However, despite the presence of modern technologies, a patient-specific approach and solid craftsmanship remain the key factors in this elective surgery.


Family caregiving: measurement of emotional well-being and various aspects of the caregiving role.
Past research and instrument development in caregiving have focused on specific aspects of caregiving or specific disability groups. This paper reports the scale characteristics of a new generic instrument developed to assess the experience of caregiving, and the social and emotional well-being of caregivers and a comparison group of 'non-caregivers'. Using computer-assisted telephone technology, a random survey of 26000 households was conducted in Victoria, Australia to identify and interview 976 caregivers of people who were aged or had a long-term illness or disability of any kind, and 219 non-caregivers. Both groups were re-interviewed after 15 months. Scales administered on each occasion to caregivers and non-caregivers included life satisfaction, positive and negative affect, social support and overload; and to caregivers, caring role satisfaction, resentment and anger, and, in relation to the care recipient, measures of help provided and needed, severity of disability and behaviour problems. On each occasion and with each sample all scales demonstrated a satisfactory reliability. With a subsample of caregiver-care-recipient dyads (N = 67), caregiver reports of severity of disability, level of helped needed and provided were validated externally by clinician assessments. A comprehensive instrument to assess the experience of caregiving was developed. It is relevant to a broad range of ages, levels and types of disability and care provided; and, in assessing health and well-being, to both caregivers and non-caregivers. Scales, including both positive and negative dimensions, have demonstrated good internal consistency on two occasions. The instrument is potentially useful in a range of research and practical settings.


Early stages of functional diversification in the Rab GTPase gene family revealed by genomic and localization studies in Paramecium species.
New gene functions arise within existing gene families as a result of gene duplication and subsequent diversification. To gain insight into the steps that led to the functional diversification of paralogues, we tracked duplicate retention patterns, expression-level divergence, and subcellular markers of functional diversification in the Rab GTPase gene family in three Paramecium aurelia species. After whole-genome duplication, Rab GTPase duplicates are more highly retained than other genes in the genome but appear to be diverging more rapidly in expression levels, consistent with early steps in functional diversification. However, by localizing specific Rab proteins in Paramecium cells, we found that paralogues from the two most recent whole-genome duplications had virtually identical localization patterns, and that less closely related paralogues showed evidence of both conservation and diversification. The functionally conserved paralogues appear to target to compartments associated with both endocytic and phagocytic recycling functions, confirming evolutionary and functional links between the two pathways in a divergent eukaryotic lineage. Because the functionally diversifying paralogues are still closely related to and derived from a clade of functionally conserved Rab11 genes, we were able to pinpoint three specific amino acid residues that may be driving the change in the localization and thus the function in these proteins.


Adaptation of Group B Coxsackie virus to adult mouse pancreas.
An alteration of tissue tropism of a Coxsackie virus has been observed following different methods of propagation of the virus in animals. Tropism for the adult mouse pancreas, as described by Pappenheimer, appeared to be irrevocably lost following prolonged brain-to-brain transfer. It was present in the same strain on reisolation from human feces, was intensified following pancreas transfers, and suppressed by brain transfers. Pancreatotropism may be correlated with the titer of virus in the pancreas.


The Co-N-C Catalyst Synthesized With a Hard-Template and Etching Method to Achieve Well-Dispersed Active Sites for Ethylbenzene Oxidation.
Biomass obtained from organic residues gradually becomes one of the optimal renewable feedstock of value added chemicals. Herein, the Co-N-C catalyst was prepared via a hard-template and etching method using the casein as C and N sources, magnesium oxide as the template, and cobalt porphyrin as the metal precursor. The obtained Co-N-C catalyst exhibited excellent catalytic performance for selective oxidation of ethylbenzene with a conversion rate of 96.5% under mild conditions. Moreover, the catalysts were investigated by techniques such as BET, XRD, Raman, transmission electron microscopic (TEM), and X-ray photoelectron spectroscopy (XPS). The results showed that the etching progress could improve the dispersion of Co and the exposure of active sites. Herein, the efficient oxidation of ethylbenzene was attributed to the well-dispersed Co-N species and the increased specific surface area.


Diffusing diffusivity: Rotational diffusion in two and three dimensions.
We consider the problem of calculating the probability distribution function (pdf) of angular displacement for rotational diffusion in a crowded, rearranging medium. We use the diffusing diffusivity model and following our previous work on translational diffusion [R. Jain and K. L. Sebastian, J. Phys. Chem. B 120, 3988 (2016)], we show that the problem can be reduced to that of calculating the survival probability of a particle undergoing Brownian motion, in the presence of a sink. We use the approach to calculate the pdf for the rotational motion in two and three dimensions. We also propose new dimensionless, time dependent parameters, αrot,2D and αrot,3D, which can be used to analyze the experimental/simulation data to find the extent of deviation from the normal behavior, i.e., constant diffusivity, and obtain explicit analytical expressions for them, within our model.


Interventions for improving mealtime experiences in long-term care.
Poor food intake in residents living in long-term care (LTC) homes is a common problem. The mealtime experience is known to be important in the multifactorial causes of food intake. Diverse interventions have been developed, implemented, and/or evaluated to improve the mealtime experience in LTC; it is possible that multicomponent interventions will have a greater benefit than single activities. To identify the range of feasible and potentially useful interventions for including in a multicomponent intervention, this scoping review identified and summarized 58 studies that described and/or evaluated mealtime experience interventions. There were several randomized controlled trials, although most studies used less rigorous methods. Interventions that are multicomponent (e.g., food service, dining environment, staff education) and target multilevel factors (e.g., residents, staff) in LTC appear to be feasible, with a variety of outcomes measured. Further research is still needed with more rigorously designed studies, confirming effectiveness, feasible implementation, and scaling up of efficacious interventions.


Dynamics of continuous stirred-tank biochemical reactor utilizing inhibitory substrate.
The model of a continuous-stirred tank biochemical reactor was developed in which the instant uptake rate of substrate was used. The solutions of the model found for the oxidation of phenol by Pseudomonas putida fitted the experimental data better than the results obtained from the models cited in the literature. The model enables control of the culture parameters so that the unwanted washout of the biomass from the bioreactor can be avoided. A review of the models cited in the literature is also presented.


Transcranial stimulation parameters to elicit motor evoked potentials.
We studied effectiveness of single, paired, and repetitive transcranial electrical stimulation to activate motor cortex in patients during spine surgery. In ten consented patients, the latency and amplitude of the muscle action potential from abductor pollicis brevis muscle after cortical stimulation was measured. The number of responses evoked by double (pair) pulse stimulation was significantly higher than that evoked by single pulse (p = 0.0191). A similar finding was obtained between the repetitive and single pulse stimulation (p = 0.0001). The repetitive stimulation was more effective than the double pulse stimulation (p = 0.0253). An increase of interstimulus interval (ISI), between pulses, from 1-3 msec did not significantly alter latency (p > 0.05) or amplitude (p > 0.05) with the double pulse or repetitive stimulations. The latency or amplitude did not significantly change with varying number of electrical pulses from 3-9. This study shows that the intraoperative repetitive transcranial stimulation is the most effective method to activate descending motor tracts under anesthesia.


Pulmonary Artery Sarcoma Detected on 18F-FDG PET/CT With Unusual Findings.
A 32-year-old woman, who presented with "sharp pain" in the right chest for more than 1 month and worsening dyspnea and fever for 10 days, was initially thought to have a pulmonary embolism. Cardiac ultrasound showed an ill-defined echogenic mass within the pulmonary trunk. F-FDG PET/CT was performed for further evaluation. PET/CT showed an intense hypermetabolism in the main, bilateral proximal, and the right main pulmonary arteries, suggesting the presence of a malignant lesion. Biopsy confirmed the lesion as a primary pulmonary artery sarcoma.


[Meta-analysis of association between pentachlorophenol exposure and cancer risk].
The epidemiological data based on the exposure of pentachlorophenol (PCP) and cancer incidence and mortality were analyzed to study the relationship between PCP exposure and cancer risk. According to the online search of relevant literatures, Poisson regression was used to analyze mortality rates for major cancer sites and fixed-effect model was employed to assess cancer SMR. The dose-response relationship between PCP exposure and cancer risk was also analyzed. Major cancer mortality rates of exposure populations researched in American and Canadian studies were approximate to or lower than national male cancer mortality rates respectively. The incidence rate of colorectal cancer in occupational exposure population was over 16.4 times in comparison with the population exposed from to drinking water and food. The pooled SMR value of kidney cancer was 1.34 (95% CI 1.02-1.77). The pooled RR for major cancer mortality increased with the rise of PCP exposure level. A potential dose-response relationship between PCP exposure and cancer risk could exist. In comparison with to the population to exposed from the drinking water and food, the risk of colorectal cancer in occupational exposure population was higher. PCP may be one of the risk factors of the kidney cancer in occupational exposure population.


An extended model for chirality selection in single-walled carbon nanotubes.
The chirality selective production of single-walled carbon nanotubes (SWCNTs) continues to represent one of the most important technological challenges. In this study, an extended model which considers all steps of the SWCNT growth process, including adsorption, decomposition, diffusion, and incorporation, is applied, for the first time, to obtain chirality selection in the SWCNT populations. We show that the dependence of the population distribution on chirality, defined as a product of the nucleation probability and the growth rate, has a volcano-shape. The model is in good agreement with the reported experimental studies and supports the results which show the surplus of near armchair or near zigzag SWCNTs. The present work emphasizes the role of the catalyst in chirality selection via optimization of chemisorption strength between the carbon species and the catalyst surface needed to achieve stable nucleation and fast growth rates. The obtained results can be used in catalyst designs to define the pathways towards the growth of SWCNTs with specific chiralities exhibiting distinguished electronic properties.


The coupling of metabolic to secretory events in pancreatic islets: does hexose transport affect cationic fluxes?
Poorly metabolized hexoses, such as 3-O-methyl-D-glucose, 2-deoxy-D-glucose and D-galactose failed to reproduce the inhibition of 86Rb outflow, the early inhibition and secondary rise in 45Ca efflux and the stimulation of insulin release evoked by D-glucose in perifused rat islets. Insulin release induced by either D-glucose or 2-ketoisocaproate was also unaffected by 3-O-methyl-D-glucose. It is concluded that hexose transport in islet cells does not represent in itself a significant determinant of the cationic and secretory response to D-glucose.


Improving heart rate estimation in preterm infants with bivariate point process analysis of heart rate and respiration.
Accurate estimation of heart rate dynamics in preterm infants is important for predicting recurrent episodes of severe bradycardia. We hypothesize that estimation of heart rate can be improved by including respiration as a state variable, based on mechanisms that underlie cardio-respiratory coherence. For ten preterm infants, we demonstrate that including respiration as a covariate improves estimation accuracy by an average of 11% across bradycardia severity, and reduces the maximum error by 8%. We also find that cardio-respiratory coherence increases in low frequency content just prior to severe bradycardia. Thus, incorporating respiratory information may improve models of heart rate dynamics and narrow potential features for bradycardia prediction.


Genome-scale mutational signatures of aflatoxin in cells, mice, and human tumors.
Aflatoxin B1 (AFB1) is a mutagen and IARC (International Agency for Research on Cancer) Group 1 carcinogen that causes hepatocellular carcinoma (HCC). Here, we present the first whole-genome data on the mutational signatures of AFB1 exposure from a total of >40,000 mutations in four experimental systems: two different human cell lines, in liver tumors in wild-type mice, and in mice that carried a hepatitis B surface antigen transgene-this to model the multiplicative effects of aflatoxin exposure and hepatitis B in causing HCC. AFB1 mutational signatures from all four experimental systems were remarkably similar. We integrated the experimental mutational signatures with data from newly sequenced HCCs from Qidong County, China, a region of well-studied aflatoxin exposure. This indicated that COSMIC mutational signature 24, previously hypothesized to stem from aflatoxin exposure, indeed likely represents AFB1 exposure, possibly combined with other exposures. Among published somatic mutation data, we found evidence of AFB1 exposure in 0.7% of HCCs treated in North America, 1% of HCCs from Japan, but 16% of HCCs from Hong Kong. Thus, aflatoxin exposure apparently remains a substantial public health issue in some areas. This aspect of our study exemplifies the promise of future widespread resequencing of tumor genomes in providing new insights into the contribution of mutagenic exposures to cancer incidence.


NMDA receptor blockade with memantine attenuates white matter injury in a rat model of periventricular leukomalacia.
Hypoxia-ischemia (H/I) in the premature infant leads to white matter injury termed periventricular leukomalacia (PVL), the leading cause of subsequent neurological deficits. Glutamatergic excitotoxicity in white matter oligodendrocytes (OLs) mediated by cell surface glutamate receptors (GluRs) of the AMPA subtype has been demonstrated as one factor in this injury. Recently, it has been shown that rodent OLs also express functional NMDA GluRs (NMDARs), and overactivation of these receptors can mediate excitotoxic OL injury. Here we show that preterm human developing OLs express NMDARs during the PVL period of susceptibility, presenting a potential therapeutic target. The expression pattern mirrors that seen in the immature rat. Furthermore, the uncompetitive NMDAR antagonist memantine attenuates NMDA-evoked currents in developing OLs in situ in cerebral white matter of immature rats. Using an H/I rat model of white matter injury, we show in vivo that post-H/I treatment with memantine attenuates acute loss of the developing OL cell surface marker O1 and the mature OL marker MBP (myelin basic protein), and also prevents the long-term reduction in cerebral mantle thickness seen at postnatal day 21 in this model. These protective doses of memantine do not affect normal myelination or cortical growth. Together, these data suggest that NMDAR blockade with memantine may provide an effective pharmacological prevention of PVL in the premature infant.


Attenuation of Mycoplasma hyopneumoniae Strain ES-2 and Comparative Genomic Analysis of ES-2 and Its Attenuated Form ES-2L.
Mycoplasma hyopneumoniae causes swine respiratory disease worldwide. Due to the difficulty of isolating and cultivating M. hyopneumoniae, very few attenuated strains have been successfully isolated, which hampers the development of attenuated vaccines. In order to produce an attenuated M. hyopneumoniae strain, we used the highly virulent M. hyopneumoniae strain ES-2, which was serially passaged in vitro 200 times to produce the attenuated strain ES-2L, and its virulence was evidenced to be low in an animal experiment. In order to elucidate the mechanisms underlying virulence attenuation, we performed whole-genome sequencing of both strains and conducted comparative genomic analyses of strain ES-2 and its attenuated form ES-2L. Strain ES-2L showed three large fragment deletion regions including a total of 18 deleted genes, compared with strain ES-2. Analysis of single-nucleotide polymorphisms (SNPs) and indels indicated that 22 dels were located in 19 predicted coding sequences. In addition to these indels, 348 single-nucleotide variations (SNVs) were identified between strains ES-2L and ES-2. These SNVs mapped to 99 genes where they appeared to induce amino acid substitutions and translation stops. The deleted genes and SNVs may be associated with decreased virulence of strain ES-2L. Our work provides a foundation for further examining virulence factors of M. hyopneumoniae and for the development of attenuated vaccines.


HLA-I Evolutionary Divergence Confers Response to PD-1 Blockade plus Chemotherapy in Untreated Advanced Non-Small Cell Lung Cancer.
PD-1 blockade plus chemotherapy has become the new standard of care in patients with untreated advanced non-small cell lung cancer (NSCLC), whereas predictive biomarkers remain undetermined. We integrated clinical, genomic, and survival data of 427 NSCLC patients treated with first-line PD-1 blockade plus chemotherapy or chemotherapy from two phase III trials (CameL and CameL-sq) and investigated the predictive and prognostic value of HLA class I evolutionary divergence (HED). High HED could predict significantly improved objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) in those who received PD-1 blockade plus chemotherapy [in the CameL trial, ORR: 81.8% vs. 53.2%; P = 0.032; PFS: hazard ratio (HR), 0.47; P = 0.012; OS: HR, 0.40; P = 0.014; in the CameL-sq trial, ORR: 89.2% vs. 62.3%; P = 0.007; PFS: HR, 0.49; P = 0.005; OS: HR, 0.38; P = 0.002], but not chemotherapy. In multivariate analysis adjusted for PD-L1 expression and tumor mutation burden, high HED was independently associated with markedly better ORR, PFS, and OS in both trials. Moreover, the joint utility of HED and PD-L1 expression showed better performance than either alone in predicting treatment benefit from PD-1 blockade plus chemotherapy. Single-cell RNA sequencing of 58,977 cells collected from 11 patients revealed that tumors with high HED had improved antigen presentation and T cell-mediated antitumor immunity, indicating an inflamed tumor microenvironment phenotype. These findings suggest that high HED could portend survival benefit in advanced NSCLC treated with first-line PD-1 blockade plus chemotherapy. See related commentary by Dimou, p. 4706.


Structural insight into mitochondrial β-barrel outer membrane protein biogenesis.
In mitochondria, β-barrel outer membrane proteins mediate protein import, metabolite transport, lipid transport, and biogenesis. The Sorting and Assembly Machinery (SAM) complex consists of three proteins that assemble as a 1:1:1 complex to fold β-barrel proteins and insert them into the mitochondrial outer membrane. We report cryoEM structures of the SAM complex from Myceliophthora thermophila, which show that Sam50 forms a 16-stranded transmembrane β-barrel with a single polypeptide-transport-associated (POTRA) domain extending into the intermembrane space. Sam35 and Sam37 are located on the cytosolic side of the outer membrane, with Sam35 capping Sam50, and Sam37 interacting extensively with Sam35. Sam35 and Sam37 each adopt a GST-like fold, with no functional, structural, or sequence similarity to their bacterial counterparts. Structural analysis shows how the Sam50 β-barrel opens a lateral gate to accommodate its substrates.


Pollen morphological variation of Berberis L. from Pakistan and its systematic importance.
Due to overlapping and diverse morphological characters, Berberis is among the most taxonomically complex genera. Palynology is one of the taxonomic tools for delimitation and identification of complex species. In this study, pollens of 10 Berberis species were analyzed through light and scanning electron microscopy. Qualitative as well as quantitative features (pollen shape, size, presence or absence of colpi, colpi length and width, exine thickness, ornamentation, pollen class, aperture, and polar-equatorial ratio) were measured. Five species were observed to have colpate (pantocolpate) with elongated ends, radially symmetrical, isopolar, monads, and psilate-regulate pollens. In polar view, six pollen were spheroidal, two were ovoid, one spherical, and one oblate. Similarly, variation in pollen length was prominent and the largest pollen on polar view was recorded for B. psodoumbellata 60-65 μm (62.4 ± 0.9), while the smallest one was observed for B. lycium 29-35 μm (32.2 ± 1). The observed variation in both quantitative and qualitative features were important in taxonomic identification. This shows that palynological characters are helpful in identification of Berberis genus at the species level.


Angioinvasion in breast carcinoma. An immunohistochemical study of factor VIII-related antigen.
Histologic sections from 63 patients with infiltrating duct carcinoma of the breast were selected for study by immunohistochemical staining with antibody against human Factor VIII-related antigen. Of these 63, 30 had no lymph node metastases at the time of surgery, while 33 had axillary lymph node metastases. A positive correlation exists between the presence of vascular invasion and lymph node metastases. Sixty-nine percent of patients with lymph node metastases had vascular invasion while only 26% of patients without lymph node metastases showed evidence of invasion of blood vessels. The finding of vascular invasion by tumor in patients without axillary lymph node metastases at the time of mastectomy may explain the occurrence of disseminated disease years after treatment.


Reversible Change between Excimer and Monomer Forms of Perylene Induced by Water Absorption and Dehydration of Poly-N-isopropylacrylamide Gel.
Several fluorescence patterns derived from the excimer states of perylene have been reported, but most of these have been obtained from rigid forms such as crystals or for perylene embedded in hard polymers. We observed perylene excimer emission on absorption of water by a poly-N-isopropylacrylamide gel containing perylene molecules, which were not fixed to the gel framework by chemical bonding. We propose that this emission arises because the hydrophobic perylene molecules cannot dissolve in water and form aggregates. The perylene aggregation was quickly lost on dehydration of the gel, and the luminescence reverted to that of the monomer. In a dehydrated environment, perylene was rapidly dispersed in the gel network. In other words, solid-liquid phase separation of perylene was induced by uptake of water into the gel, and perylene dissolved in the gel on dehydration. Because the outside of the gel is always in an aqueous environment, perylene will remain semipermanently in the gel. Therefore, monomer emission and excimer emission can be switched reversibly and repeatedly.


Epithelial cells in tissue culture.
In this review the characteristics of established renal and intestinal epithelial cell lines are described by summarizing the accumulated literature about specific properties retained by the cells in tissue culture. Furthermore, brief examples are given for the use of cultured epithelia as model systems to study epithelial transport and metabolic functions, epithelial cell polarity, and aspects of the differentiation and maturation of epithelia by physiological, biochemical and genetic, or cell and molecular biological approaches.


Evaluation of the distance from the anterior cervicovaginal junction to the anterior peritoneal reflection for anterior colpotomy during vaginal hysterectomy in Korean women.
This study aimed to know the distance of the cervicovaginal junction (CVJ) to the anterior peritoneal reflection (APR) as measured in surgical specimens, and assess the distance between the CVJ and APR to ensure safe anterior colpotomy for vaginal hysterectomy among Korean women.Patients who underwent vaginal hysterectomy were included in the analysis. According to the presence of pelvic organ prolapse or menopausal status, the distance from the CVJ to the APR was assessed preoperatively through transvaginal ultrasonography (TV-US), as well as intraoperatively using surgical specimens. The intraclass correlation coefficient was used to determine the reliability between 2 measurements.In total, 171 patients were included. The median distance from the CVJ to the APR measured on TV-US was 19.8 (3.3-41.3) mm. Meanwhile, the median distance from the CVJ to the APR measured using the surgical specimen was 26.0 (12.0-55.0) mm. The intraclass correlation coefficient for the absolute agreement between 2 measurements was 0.353 (95% confidence interval: 0.002-0.570; P < .001), which is indicative of poor reliability. The median distance from the CVJ to the APR measured using the surgical specimen did not differ significantly between the 2 groups according to pelvic organ prolapse (26.0 [12.0-55.0] vs 27.5 [17.0-55.0] mm, P = .076] and menopausal status (27.0 [15.0-55.0] vs 26.0 [12.0-55.0] mm, P = .237).TV-US does not an accurately measure the dissection plane length from the CVJ to the APR during anterior colpotomy. During vaginal hysterectomy, the median distance from the CVJ to the APR measured using the surgical specimen was 26 (12.0-55.0) mm, which can help decrease surgical complications.


Irregular word reading as a marker of cognitive and semantic decline in Alzheimer's disease rather than an estimate of premorbid intellectual abilities.
Irregular word reading has been used to estimate premorbid intelligence in Alzheimer's disease (AD) dementia. However, reading models highlight the core influence of semantic abilities on irregular word reading, which shows early decline in AD. The general aim of this study is to determine whether irregular word reading is a valid estimate of premorbid intelligence, or a marker of cognitive and semantic decline in AD. 681 healthy controls (HC), 104 subjective cognitive decline, 290 early and 589 late mild cognitive impairment (EMCI, LMCI) and 348 AD participants from the Alzheimer's Disease Neuroimaging Initiative were included. Irregular word reading was assessed with the American National Adult Reading Test (AmNART). Multiple linear regressions were conducted predicting AmNART score using diagnostic category, general cognitive impairment and semantic tests. A generalized logistic mixed-effects model predicted correct reading using extracted psycholinguistic characteristics of each AmNART words. Deformation-based morphometry was used to assess the relationship between AmNART scores and voxel-wise brain volumes, as well as with the volume of a region of interest placed in the left anterior temporal lobe (ATL). EMCI, LMCI and AD patients made significantly more errors in reading irregular words compared to HC, and AD patients made more errors than all other groups. Across the AD continuum, as well as within each diagnostic group, irregular word reading was significantly correlated to measures of general cognitive impairment / dementia severity. Neuropsychological tests of lexicosemantics were moderately correlated to irregular word reading whilst executive functioning and episodic memory were respectively weakly and not correlated. Age of acquisition, a primarily semantic variable, had a strong effect on irregular word reading accuracy whilst none of the phonological variables significantly contributed. Neuroimaging analyses pointed to bilateral hippocampal and left ATL volume loss as the main contributors to decreased irregular word reading performances. Irregular word reading performances decline throughout the AD continuum, and therefore, premorbid intelligence estimates based on the AmNART should not be considered accurate in MCI or AD. Results are consistent with the theory of irregular word reading impairments as an indicator of disease severity and semantic decline.


Phasing and imputation of single nucleotide polymorphism data of missing parents of biparental plant populations.
This paper presents an extension to a heuristic method for phasing and imputation of genotypes of descendants in biparental populations so that it can phase and impute genotypes of parents that are ungenotyped or partially genotyped. The imputed genotypes of the parent are used to impute low-density (Ld) genotyped descendants to high density (Hd). The extension was implemented as part of the AlphaPlantImpute software and works in three steps. First, it identifies whether a parent has no or Ld genotypes and identifies its relatives that have Hd genotypes. Second, using the Hd genotypes of relatives, it determines whether the parent is homozygous or heterozygous for a given locus. Third, it phases heterozygous positions of the parent by matching haplotypes to its relatives. We measured the accuracy (correlation between true and imputed genotypes) of imputing parent genotypes in simulated biparental populations from different scenarios. We tested the imputation accuracy of the missing parent's descendants using the true genotype of the parent and compared this with using the imputed genotypes of the parent. Across all scenarios, the imputation accuracy of a parent was >0.98 and did not drop below ∼0.96. The imputation accuracy of a parent was always higher when it was inbred than outbred. Including ancestors of the parent at Hd, increasing the number of crosses and the number of Hd descendants increased the imputation accuracy. The high imputation accuracy achieved for the parent translated to little or no impact on the imputation accuracy of its descendants.


Nutrition and the older adult.
The importance of ensuring adequate nutrition in older people is often acknowledged but, the evidence suggests, theory is not always matched by practice. This article describes causes of malnutrition in older adults and discusses nursing strategies to prevent it occurring.


Nosocomial methicillin resistant Staphylococcus aureus pneumonia - epidemiology and trends based on data of a network of 586 German ICUs (2005-2009).
The epidemiology of MRSA pneumonia varies across countries. One of the most import risk factors for the development of nosocomial MRSA pneumonia is mechanical ventilation. Methicillin resistance in S. aureus ventilator associated pneumonia (VAP) ranged between 37 % in German, 54 % in the US American and 78 % in Asian and Latin American ICUs. In 2009, the incidence density of nosocomial VAP caused by MRSA was 0.28 per 1000 ventilation days in a network of 586 German ICUs. Incidences peaked in neurological and neurosurgical ICUs. Crude hospital mortality in studies performed after 2005 lay between 27 % and 59 % and attributable MRSA pneumonia mortality at 40 %. Since 2005, US American and German data indicate decreasing trends for MRSA pneumonia. Measures to reduce MRSA pneumonia or to control the spread of MRSA include hand hygiene, standard and contact precautions, oral contamination with chlorhexidine, skin decontamination with antiseptics, screening, and (possibly) patient isolation in a single room.


A clinical evaluation of the Maquet Quadrox-i Neonatal oxygenator with integrated arterial filter.
High-performance, low-prime-volume oxygenators for the pediatric patient population have become a growing market among manufacturers. In the summer of 2011, our institution clinically evaluated the performance of the newly released Maquet Quadrox-i Neonatal oxygenator with integrated arterial filter. The static priming volume, including the integrated arterial filter, is 40 ml and the maximum rated blood flow is 1.5 liters per minute (LPM). The device was used on seven pediatric patients, ranging from 3.2 to 14 kg, undergoing various congenital heart defect repairs. Data were collected to calculate gas transfer, trans-oxygenator pressure drop, and heat exchange performance. The mean cardiopulmonary bypass time was 85 minutes and the mean cross-clamp time was 56 minutes. The average oxygen transfer was 34.3 ± 22.8 ml/O2/min and increased with both blood flow and FiO2. The average carbon dioxide transfer was 22.3 ± 17.8 ml/min and increased with both blood flow and gas sweep to blood flow ratio. The average trans-oxygenator pressure drop per blood flow was 53.3 ± 15.5 mmHg/L/min and increased with flow. The average heat exchanger performance factor was 47.6 ± 11.6% and decreased with flow. The heat exchange performance factor at maximum observed clinical flow, 1.42 LPM, was 36.4%. During this evaluation, the Maquet Quadrox-i Neonatal oxygenator adequately performed within its operational flow in the clinical setting.


Genetic variation of temperature-regulated curd induction in cauliflower: elucidation of floral transition by genome-wide association mapping and gene expression analysis.
Cauliflower (Brassica oleracea var. botrytis) is a vernalization-responsive crop. High ambient temperatures delay harvest time. The elucidation of the genetic regulation of floral transition is highly interesting for a precise harvest scheduling and to ensure stable market supply. This study aims at genetic dissection of temperature-dependent curd induction in cauliflower by genome-wide association studies and gene expression analysis. To assess temperature-dependent curd induction, two greenhouse trials under distinct temperature regimes were conducted on a diversity panel consisting of 111 cauliflower commercial parent lines, genotyped with 14,385 SNPs. Broad phenotypic variation and high heritability (0.93) were observed for temperature-related curd induction within the cauliflower population. GWA mapping identified a total of 18 QTL localized on chromosomes O1, O2, O3, O4, O6, O8, and O9 for curding time under two distinct temperature regimes. Among those, several QTL are localized within regions of promising candidate flowering genes. Inferring population structure and genetic relatedness among the diversity set assigned three main genetic clusters. Linkage disequilibrium (LD) patterns estimated global LD extent of r(2) = 0.06 and a maximum physical distance of 400 kb for genetic linkage. Transcriptional profiling of flowering genes FLOWERING LOCUS C (BoFLC) and VERNALIZATION 2 (BoVRN2) was performed, showing increased expression levels of BoVRN2 in genotypes with faster curding. However, functional relevance of BoVRN2 and BoFLC2 could not consistently be supported, which probably suggests to act facultative and/or might evidence for BoVRN2/BoFLC-independent mechanisms in temperature-regulated floral transition in cauliflower. Genetic insights in temperature-regulated curd induction can underpin genetically informed phenology models and benefit molecular breeding strategies toward the development of thermo-tolerant cultivars.


Comparison of Postoperative Safety, Efficacy, and Visual Quality after SMILE for Myopic Patients with Different Corneal Thicknesses.
To investigate the safety, efficacy, and visual quality of small incision lenticule extraction (SMILE) in different corneal thickness patients with myopia or myopic astigmatism. This prospective cohort study included 191 right eyes of 191 patients. Eyes were divided into three groups according to preoperative central corneal thickness (CCT) (Preoperative central corneal thickness (CCT) was the group indicator.) There were 31 eyes in the thin cornea group (CCT ≤500 um (μm), TC), 94 eyes in the moderate corneal thickness group (CCT ≥501 um (μm) and ≤550 um (μm), MD) and 66 eyes in the thick cornea group (CCT ≥550 um (μm), TK). Comparisons in uncorrected (UDVA) and best-corrected distance visual acuity (BDVA), manifest refractive spherical equivalent (SE), preoperative mesopic/photopic contrast sensitivity (CS), ocular higher-order aberrations (HOAs) at a 6mm analytical pupil diameter, and visual quality questionnaires were made (performed) among the three groups during the postoperative six months. Subgroup analyses were made based on preoperative SE. The safety indices at six months were 1.15 ± 0.18, 1.14 ± 0.17, and 1.18 ± 0.17, respectively (p = 0.374), and the efficacy indices at six months were 1.07 ± 0.25, 1.12 ± 0.22, and 1.11 ± 0.21, respectively (p = 0.599). The postoperative SE was -0.07 ± 0.52D, -0.14 ± 0.38D, and -0.05 ± 0.46D after SMILE in the three groups, respectively (p = 0.376). No significant difference was found in mesopic/photopic CS, HOAs, and visual quality among different corneal thickness groups and SE groups. Postoperative SE and efficacy indices were the lowest in thin cornea eyes with ultra-high myopia (over -9.00 D). SMILE provides comparable safety, efficacy, and visual quality results in different corneal thickness patients. Those with myopia higher than -9.00 D had less efficacy after surgery, especially in thin cornea patients.


Lyme Disease Presenting as a Spontaneous Knee Effusion.
Musculoskeletal complaints, which are frequently associated with Lyme disease, often prompt patients to see a physician. In particular, transient episodes of spontaneous knee effusion are common early in the progression of Lyme disease, and, if left untreated, 60% of patients diagnosed with the disease develop Lyme arthritis. This disease is easily treated with antibiotics; therefore, inclusion of Lyme disease in the differential diagnosis as a potential cause of a spontaneous knee effusion can prevent the development of more severe symptoms associated with the disease. However, the time required to receive test results and the inconsistencies between serum and synovial tests can complicate diagnosis of the disease.


Cockarde nevus: a case report and review of the literature.
Benign acquired melanocytic nevi usually display an even and uniform architecture and coloration easily recognized by the dermatologist. The cockarde nevus, a variant of the melanocytic nevus, is an exception. It displays a targetlike morphology with histologic characteristics of a compound nevus. We believe because the lesion has been rarely reported in the American literature, it is often mistaken in this country for a dysplastic nevus.


Virtual screening on natural products for discovering active compounds and target information.
Natural products, containing inherently large-scale structural diversity than synthetic compounds, have been the major resources of bioactive agents and will continually play as protagonists for discovering new drugs. However, how to access this diverse chemical space efficiently and effectively is an exciting challenge for medicinal chemists and pharmacologists. While virtual screening, which has shown a great promise in drug discovery, will play an important role in digging out lead (active) compounds from natural products. This review focuses on the strategy of virtual screening based on molecular docking and, with successful examples from our laboratory, illustrates the efficiency of virtual screening in discovering active compounds from natural products. On the other hand, the sequencing of the human genome and numerous pathogen genomes has resulted in an unprecedented opportunity for discovering potential new drug targets. Chemogenomics has appeared as a new technology to initiate target discovery by using active compounds as probes to characterize proteome functions. Natural products are the ideal probes for such research. Binding affinity fingerprint is a powerful chemogenomic descriptor to characterize both small molecules and pharmacologically relevant proteins. Therefore, this review also discusses binding affinity fingerprint strategy for identifying target information from the genomic data by using natural products as the probes.


Novel microbial transformations of sclareolide.
Fungal catalysis of sclareolide (1) using Mucor plumbeus (ATCC 4740), Cunninghamella blakesleeana (ATCC 9245), Cunninghamella echinulata (ATCC 9244), Curvularia lunata (ATCC 12017) and Aspergillus niger (ATCC 1004), was performed. Cunninghamella blakesleeana (ATCC 9245) metabolized compound 1 to afford O(6)-sclareolide (2), 3beta,6alpha-dihydroxysclareolide (3), 9-hydroxysclareolide (4), along with three known metabolites, 1beta,3beta-dihydroxysclareolide (5), 3-oxosclareolide (6) and 3beta-hydroxysclareolide (7). Biotransformation experiments of compound 1 with Cunninghamella echinulata (ATCC 9244) also yielded two new compounds, 5-hydroxysclareolide (8), and 7beta-hydroxysclareolide (9) along with two known compounds 5 and 7. Spectroscopic methods were used to establish the structures of compounds 2-9. Compounds 2-9 exhibited modest acetylcholinesterase inhibitory activity.


Sex differences in a virtual water maze: an eye tracking and pupillometry study.
Sex differences in human spatial navigation are well known. However, the exact strategies that males and females employ in order to navigate successfully around the environment are unclear. While some researchers propose that males prefer environment-centred (allocentric) and females prefer self-centred (egocentric) navigation, these findings have proved difficult to replicate. In the present study we examined eye movements and physiological measures of memory (pupillometry) in order to compare visual scanning of spatial orientation using a human virtual analogue of the Morris Water Maze task. Twelve women and twelve men (average age=24 years) were trained on a visible platform and had to locate an invisible platform over a series of trials. On all but the first trial, participants' eye movements were recorded for 3s and they were asked to orient themselves in the environment. While the behavioural data replicated previous findings of improved spatial performance for males relative to females, distinct sex differences in eye movements were found. Males tended to explore consistently more space early on while females demonstrated initially longer fixation durations and increases in pupil diameter usually associated with memory processing. The eye movement data provides novel insight into differences in navigational strategies between the sexes.


Assessment of the role of an omega loop of cholesterol oxidase: a truncated loop mutant has altered substrate specificity.
The function of an active site loop (70-90) of cholesterol oxidase has been ascertained by deleting five contiguous residues (79-83) from the tip of the loop. From the crystal structure of the wild-type enzyme, it appears that this truncation will not significantly perturb the structure of the rest of the enzyme. The UV/vis and CD spectra of the mutant confirm that the enzyme is properly folded with FAD bound. The mutant enzyme still transfers 2H from the 4beta-carbon of the intermediate, cholest-5-en-3-one, to the 6beta-carbon of the product, cholest-4-en-3-one, during isomerization. The kcat/Km of the mutant is increased 6-fold with dehydroepiandrosterone as substrate. Thus, the enzyme is still catalytically active after deletion of the five loop-tip residues. With micellar cholesterol, the kcat/Km of the mutant is decreased 170-fold relative to wild type. This suggests that the tip of the loop is necessary for packing with the "tail" of cholesterol and is responsible for substrate specificity at C17. Increased release of intermediate cholest-5-en-3-one in the mutant-catalyzed reaction is not observed. Truncation of the loop, therefore, does not affect the grip of the enzyme on the intermediate. With lipid vesicle substrates (egg phosphatidylcholine/cholesterol, 1:1), the initial velocity of the mutant is reduced 3000-fold. The binding affinity for the vesicles, however, is only reduced 2-fold. Consequently, the loop is not the primary determinant of binding affinity for vesicles. It is concluded that the loop is important for movement of cholesterol from the lipid bilayer. The tip residues form a hydrophobic pathway between lipid membrane and active site to facilitate movement of substrate and product in to and out of the active site.


Treatment of Parkinson's disease with magnetic fields reduces the requirement for antiparkinsonian medications.
Recently, I reported that extracranial treatment with picoTesla range magnetic fields (MF) is an effective, safe, and revolutionary modality in the management of Parkinsonism including those patients manifesting levodopa-induced motor complications. This treatment, which has emerged as a potentially more advantageous modality than pharmacologic therapy, also produces improvements in nonmotor aspects of the disease including mood, cognitive functions, sleep, pain, appetite, autonomic functions, and sexual behavior, which are usually minimally, if at all, ameliorated by long term therapy with levodopa or anticholinergic agents. The present communication concerns a 69 year old Parkinsonian patient who, following a series of two treatments with extracranial picoTesla range MF on two separate days, improved to the point where he was able to discontinue most of his antiparkinsonian medications for a period of two weeks without experiencing deterioration in symptoms. On the third week he began to develop recurrence of symptoms and resumed taking his regular medications. At the end of the fourth week the patient received a series of four magnetic treatments on four successive days after he completely discontinued his antiparkinsonian medications. During this period he experienced a remarkable improvement in motor disability as well as in cognitive functions (i.e., visuospatial performance), mood, sleep, appetite, bowel functions and resolution of pain in the lower extremity. This report attests to the antiparkinsonian efficacy of picoTesla range MF and suggests that this treatment, when applied on a regular basis, may reduce the requirement for antiparkinsonian medications. This observation, when confirmed in a larger cohort of patients, may carry important implications for the therapy of Parkinsonism as it may offer an alternative treatment for patients who develop levodopa failure or experience intolerable side effects from dopaminergic medication. The observation that magnetic treatment improved the patient's symptoms while being off dopaminergic therapy supports the role of nondopaminergic mechanisms in the pathophysiology of Parkinsonism.


An anoxic-aerobic system for simultaneous biodegradation of phenol and ammonia in a sequencing batch reactor.
A laboratory-scale sequencing batch reactor (SBR) was investigated to treat artificial pretreated coal gasification wastewater that was mainly contained of ammonia and phenol. The efficiency of SBR fed with increasing phenol concentrations (from 150 to 300 mg l-1) and the relationship among phenol, nitrogen removal, and the microbial community structure were evaluated. When the phenol feeding concentration was increased to about 300 mg l-1, the removal efficiency was above 99.0%, demonstrating the robustness of phenol removal capacity. The study showed that most phenol was degraded in anoxic stage. The average removal efficiencies of ammonia and total nitrogen were 98.4 and 81.9%, respectively, with average NH4+-N concentration of 107.5 mg l-1 and COD/N 7.5. Low temperature caused sludge loss that led to the decreased performance. Increasing the temperature could not recover the performance effectively. The data from bacterial analysis revealed that Delftia, Hydrogenophaga, and unclassified Xanthomonadaceae played a significant role in phenol degradation before the temperature increase, while uncultured Syntrophococcus sp. and unclassified Rhodocyclaceae were responsible for phenol degradation after the temperature increase. These results imply that the SBR holds potential for the simultaneous removal of phenolic compounds and nitrogen through aerobic ammonia oxidation and anoxic denitrification with phenol as the co-organic carbon source.


In Situ Generated HypoIodite Activator for the C2 Sulfonylation of Heteroaromatic N-oxides.
A mild approach for direct C2 sulfonylation of heteroaromatic N-oxides with sulfonyl hydrazides affording 2-sulfonyl quinolines/pyridines has been developed. A variety of heteroaromatic N-oxides and sulfonyl hydrazides participate effectively in this transformation which uses hypoiodites (generated in situ from NaI and TBHP) as a means of substrate activators. In this reaction, the N-oxide plays a dual role, acting as a traceless directing group as well as a source of oxygen atom.


Legal prison tattooing centers: viable health policy initiative?
Tattooing exemplifies several important links between criminal justice systems, public health, custodial management, and the social organization and behavior of prisoners. This commentary examines the efficiency of setting up legal, prison-financed tattooing centers as a way of discouraging illicit tattooing and minimizing bloodborne disease transmission risks in prison settings. The author posits that the impact of legal prison tattooing centers is unlikely to be significant since less than 5 percent of bloodborne infectious diseases have been reliably attributable to tattooing, either in prison or in community settings. Behavioral studies indicate that prisoners at the highest risk of contracting bloodborne infections would probably not utilize legal prison tattooing services. Furthermore, such a service is likely to be very expensive relative to potential health benefits. Strategies focussed on reducing injecting drug use among prisoners will yield greater benefits for reducing bloodborne disease transmission per dollar spent compared with setting up legal prison tattooing parlors. Social marketing of temporary tattooing alternatives (eg, henna tattoos) to traditional illicit tattooing techniques in prison settings is potentially valuable, as temporary tattoos pose no infection risk and may also facilitate reduction in occupational and social stigma associated with many illicit prison tattoos.


Effects of colony-stimulating factors on leukemia progenitor cells and oncogene expression.
Realising the therapeutic potential of colony-stimulating factors (CSFs) depends upon understanding the biological responses elicited by these regulators in target hemopoietic cells, and determining the biochemical nature of signals transduced through their receptors. These signals can lead to growth, differentiation or the activation of an effector function. CSF-dependent cells maintained in culture resemble pre-leukemic cells and releasing cells from a factor-dependent growth state must be a final step in leukemogenesis. The measurement of metabolic changes in cells following ligand-receptor interactions has thus far failed to reveal the biochemical identity of growth signal transducing events. The patterns of growth responses observed in various CSF-dependent cell lines provide some idea of the relationship of these events for different CSF species. A number of IL-3-dependent cell lines can be switched to an IL-2- or a GM-CSF-dependent growth state. This implies the intracellular pathways activated by signal transduction through their different receptors must be related. The expression of the v-src oncogene in IL-3- and GM-CSF-dependent cells leads to CSF-independent growth, whereas in an IL-2-dependent growth state the expression of v-src in these same cells does not lead to a loss of the requirement for IL-2 for growth. It might be argued that signal transduction through IL-3- or GM-CSF-specific receptors involves a protein tyrosine kinase. However, the addition of IL-3 or GM-CSF to cells expressing v-src results in a decrease in tyrosine kinase activity, suggesting that the effect of IL-3- or GM-CSF-specific signal transduction is to inhibit the expression of tyrosine kinase. It is unlikely that G-CSF signal transduction involves a receptor-associated tyrosine kinase. 32Dcl-23 cells respond to G-CSF by cell division and terminal differentiation, but when these cells are transformed to factor-independent growth following v-src infection, they remain responsive to G-CSF but lose the capacity to terminally differentiate. We have investigated the growth and differentiative responses of a range of human myeloid leukemias to G-CSF, IL-3 and GM-CSF. There is heterogeneity in the responses of different leukemic cells to these growth factors.(ABSTRACT TRUNCATED AT 400 WORDS)


Childhood sexual abuse and its association with adult physical and mental health: results from a national cohort of young Australian women.
Childhood sexual abuse (CSA) occurs across the world, with a prevalence of 20% internationally. Our aim was to investigate the associations between CSA, CSA plus adult violence experiences, and selected self-reported physical and mental health in a community sample of women. Data from 7,700 women aged 28-33 years from the 1973-1978 cohort who completed Survey 4 of the Australian Longitudinal Study on Women's Health (ALSWH) were analyzed. Questions about prior abuse experience such as child sexual abuse, IPV, adult physical and sexual assaults, andphysical and mental health. Women who experienced CSA were 1.4 times more likely to experience bodily pain (adjusted odds ratio [AOR] = 1.37, confidence interval [CI] = [1.19, 1.58]), 1.3 times more likely to have poorer general health (AOR = 1.33, CI = [1.15, 1.54]), and 1.4 times more likely to be depressed in the past 3 years (AOR = 1.44, CI = [1.22, 1.71]) compared with those without abuse.. Women who experienced both CSA and adult violence were 2.4 to 3.1 times more likely to experience poor general (AOR = 2.35, CI = [1.76, 3.14]) and mental health (AOR = 2.69, CI = [1.98, 3.64]), and suffer from depression (AOR = 2.84, CI = [2.13, 3.78]) and anxiety (AOR = 3.10, CI = [2.12, 4.53]) compared with women with no abuse. This study demonstrates the importance of CSA in pain and poorer long-term mental and physical health.. It emphasizes how prior CSA may amplify pain and poorer long-term mental and physical health among women who are again exposed to violence in adulthood.


Performance of clear vacuum-formed thermoplastic retainers depending on retention protocol: a systematic review.
We aimed at comparing the performance of vacuum-formed thermoplastic retainers (VFR) worn either full-time or part-time, in maintaining orthodontic treatment results in terms of tooth alignment, arch form and occlusion. We reviewed randomized and prospective controlled clinical trials comparing VFR wearing protocols and searched databases, without restrictions, for published and unpublished literature. The risk of bias was assessed using the Cochrane Risk of Bias tool and the overall level of certainty in the evidence following ADA methodology. 184 studies were initially identified and reduced to the 3 randomized controlled trials included in the systematic review by means of specific criteria. One study followed patients 1 year into retention, and the other two for 6 months. Little's Irregularity Index, intermolar and intercanine width, arch length, overjet and PAR score did not differ significantly between the patients wearing their retainers part time or full time. We observed a slight increase in the overbite in the part-time group in only one trial. With a moderate level of certainty, we found that during the observation period, full-time VFR wear is not superior to part-time, bearing in mind the potential implications for health burden, retainer longevity and cost-effectiveness, as well as patient satisfaction and compliance.


Frequency Responses to Visual Tracking Stimuli May Be Affected by Concussion.
Human visual tracking performance is known to be reduced with an increase of the target's speed and oscillation frequency, but changes in brain states following a concussion may alter these frequency responses. The goal of this study was to characterize and compare frequency-dependent smooth pursuit velocity degradation in normal subjects and patients who had chronic postconcussion symptoms, and also examine cases of acutely concussed patients. Eye movements were recorded while subjects tracked a target that moved along a circular trajectory of 10° radius at 0.33, 0.40, or 0.67 Hz. Performance was characterized by the gain of smooth pursuit velocity, with reduced gain indicating reduced performance. The difference between normal and chronic patient groups in the pattern of decrease in the gain of horizontal smooth pursuit velocity as a function of the stimulus frequency reflected patients performing more poorly than normal subjects at 0.4 Hz while both groups performing similarly at 0.33 or 0.67 Hz. The performance of acute patients may represent yet another type of frequency response. The findings suggest that there may be ranges of stimulus frequencies that differentiate the effects of concussion from normal individuals.


Potential shortage of supplemental test kits for detecting HIV-1 antibodies.
The Public Health Service has become aware of a potential shortage of supplemental test kits used for confirmatory testing of human immunodeficiency virus (HIV) antibodies in specimens obtained from either patients or blood and plasma donors. On April 17, 2002, Calypte Biomedical Corporation (Alameda, California) announced the company might stop manufacturing the Cambridge Biotech HIV-1 Western blot kit. The distributor, bioMérieux, Inc. (Durham, North Carolina), immediately notified customers that it no longer would be able to distribute the Cambridge Biotech HIV-1 Western blot kit.


Color-Encoded Assays for the Simultaneous Quantification of Dual Cancer Biomarkers.
For the first time, the scattering light of noble nanoparticles was applied for the simultaneous detection of dual cancer biomarkers. Two nanoprobes with dual scattering light colors were used for the simultaneous imaging of alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) based on the sandwich-type immunoassay. Since AFP can combine anti-AFP-modified gold nanoparticles, which have green scattering light under the dark-field microscopic imaging (iDFM) technique, while CEA can conjugate anti-CEA-immobilized silver nanoparticles, which have blue scattering light, the simultaneous determination of AFP and CEA can be achieved by separately counting the number of green and blue light spots in iDFM. The mutual interference between the detection processes of AFP and CEA in the dual detection was investigated, and a negligible interference was found when the concentration of the antigen was in the range of 0.5-10 ng/mL, indicating the practicability of the simultaneous sensitive detection of dual targets. Furthermore, AFP and CEA in serum samples were also quantified directly without additional sample pretreatment, demonstrating the potential applications of the developed method in clinical diagnosis.


Rotational analysis of CO2 bands near 4 microm.
The rotational constants of bands of (16)O(12)C(17)O and (16)O(12)C(18)O near 2600 cm(-1) have been estimated by spectral curve fitting. These constants predict the positions of all but the weakest lines with an estimated accuracy of 0.003 cm-(1). They are in reasonable agreement with other published values, although some of these do not predict the observed line positions satisfactorily. The causes of these disagreements are discussed.


Hsc66 substrate specificity is directed toward a discrete region of the iron-sulfur cluster template protein IscU.
Hsc66 and Hsc20 comprise a specialized chaperone system important for the assembly of iron-sulfur clusters in Escherchia coli. Only a single substrate, the Fe/S template protein IscU, has been identified for the Hsc66/Hsc20 system, but the mechanism by which Hsc66 selectively binds IscU is unknown. We have investigated Hsc66 substrate specificity using phage display and a peptide array of IscU. Screening of a heptameric peptide phage display library revealed that Hsc66 prefers peptides with a centrally located Pro-Pro motif. Using a cellulose-bound peptide array of IscU we determined that Hsc66 interacts specifically with a region (residues 99-103, LPPVK) that is invariant among all IscU family members. A synthetic peptide (ELPPVKIHC) corresponding to IscU residues 98-106 behaves in a similar manner to native IscU, stimulating the ATPase activity of Hsc66 with similar affinity as IscU, preventing Hsc66 suppression of bovine rhodanese aggregation, and interacting with the peptide-binding domain of Hsc66. Unlike native IscU, however, the synthetic peptide is not bound by Hsc20 and does not synergistically stimulate Hsc66 ATPase activity with Hsc20. Our results indicate that Hsc66 and Hsc20 recognize distinct regions of IscU and further suggest that Hsc66 will not bind LPPVK motifs with high affinity in vivo unless they are in the context of native IscU and can be directed to Hsc66 by Hsc20.


[Clinicopathological Features and Outcomes of Treatment for HER2 Positive Gastric Cancer].
In March 2011, trastuzumab was approved for treating human epidermal growth factor receptor 2 (HER2) positive advanced gastric cancer (AGC) in Japan. Therefore, all patients with AGC should be evaluated for HER2 status. In this study, we analyzed the clinicopathological features and current status of treatment in HER2 positive gastric cancer. One hundred 6 gastric cancer patients were examined for HER2 expression in our hospital between March 2011 and August 2014. Sixteen patients (15.1%) were HER2 positive. There was no correlation between HER2 status and age, sex, and location of tumor; however, HER2 positivity was significantly more frequent in patients with intestinal type tumors and had a tendency towards being more frequent in patients with macroscopic types 0, 1 or 2. Trastuzumab was administered to 10 patients with HER2 positive AGC. The total number of doses of trastuzumab was 1 to 44 (median 7.5), and the therapeutic effect of trastuzumab combination chemotherapy was 1 patient with a complete response and 4 with a partial response. Adverse events due to trastuzumab were not observed. The incidence of HER2 over-expression was 15.1%, and trastuzumab combination chemotherapy was relatively safe and effective.


A distinct population of tubular cells in the distal S3 segment contributes to S3 segment regeneration in rats following acute renal failure induced by uranyl acetate.
We previously reported that early regenerating cells found at the distal area of the S3 segment of the nephron (designated as target cells) were label-retaining cells in uranyl acetate (UA)-induced acute renal failure (ARF) in rats. In this study, we examined the contribution of these target cells to S3 segment repair after UA treatment. We also discriminated target cells from bromodeoxyuridine (BrdU)-label-retaining cells labeled under normal conditions and examined their capacity to proliferate following a second insult and their resistance to 5-fluorouracil (5-FU). Target cells were labeled and tracked using a (3)H-thymidine pulse/chase approach after UA (4 mg/kg) injection to rats. Normal rats were labeled with BrdU, and cells positive for BrdU and Ki67 were analyzed after UA treatment. The kinetics of target cells was examined after a second dose of UA and treatment with 5-FU. The target cells were strongly labeled by (3)H-thymidine and were predominantly found in the distal quarter of the S3 segment until 40 weeks after generating 'label-diluted' cells throughout the S3 segment. Cells labeled with BrdU under normal conditions did not express Ki67 after UA treatment but target cells were Ki67-positive. The target cells underwent further proliferation following the second treatment with UA and were transiently arrested by 5-FU treatment at G0/G1 after UA. The target cells are slow-cycling cells, resistant to 5-FU treatment and have the capacity to undergo further proliferation following a second insult with UA. These data suggest the presence of a distinct population of cells that can regenerate the S3 segment in UA-induced ARF.


Low dose and slow titration of topiramate as adjunctive therapy in refractory partial epilepsies: a multicentre open clinical trial.
A multicentre open clinical trial was conducted to evaluate the clinical usefulness of a slower titration of topiramate (TPM) to 300 mg /day as adjunctive therapy for medically intractable partial epilepsies. Nineteen centres participated in the trial. Study patients had to have had two or more seizures per 4 weeks whilst taking maximum tolerated doses of one but not more than two anti-epileptic drugs. The starting dose of TPM was 25 mg /day and the dose was increased weekly by 25 mg /day until 100 mg /day was reached. Thereafter TPM was increased by 50 mg /day weekly up to the target dose of 300 mg /day, which was followed by an 8 week maintenance phase. Seizure outcomes were measured by intention-to-treat analysis (ITTA). Two hundred and thirteen patients entered the study. Median seizure frequency reduction rate was 44.8%, responder rate was 47.6%, and seizure free rate was 9.0%. These results were comparable to that of TPM 600 mg /day in our previous controlled trial. In subgroup analysis, seizure free rate was higher in those patients with a lower baseline seizure frequency rate. Seventeen patients (8.0%) were prematurely withdrawn from the study due to adverse events (AE) or lack of effect. One or more AEs were reported in 22% of patients, with dizziness being the most frequent AE. Other AEs occurred in less than 5% of patients. TPM 300 mg /day was effective and in conjunction with a slower dose-titration, markedly reduced the incidence of AEs, compared with previous study.


[Retroperitoneal ganglioneurinoma].
We present a case of 20-years-old female with nonspecific symptoms (intermittent abdominal pains) and blood and urine tests showed the changes connected with infection of the urinal tract. The patient was sent to further diagnostic imaging methods, because the repeated attacks of uroinfection after the applied antibiotic therapy. After the US we performed CT and MRI that indicated the existence of retroperitoneal mass which dislocated the surrounding structures (left kidney and the urether) but was not infiltrated them. US were initial method and CT and MRI have done as complementary methods providing the exact picture of the mass. After surgical treatment, ganglioneurinoma was histological diagnosed.


Investigation of de novo totally random biosequences, Part II: On the folding frequency in a totally random library of de novo proteins obtained by phage display.
We present an investigation on theoretically possible protein structures which have not been selected by evolution and are, therefore, not present on our Earth ('Never Born Proteins' (NBP)). In particular, we attempt to assess whether and to what extent such polypeptides might be folded, thus acquiring a globular protein status. A library (ca. 10(9) clones) of totally random polypeptides, with a length of 50 amino acids, has been produced by phage display. The only structural bias in these sequences is a tripeptide substrate for thrombin: PRG, chosen according to the criteria described in the preceding Part I of this series. The presence of this substrate in an otherwise totally random sequence forms the basis for a qualitative experimental criterion which distinguishes unfolded from folded proteins, as folded proteins are more protected from protease digestion than unfolded ones. The investigation of 79 sequences, randomly selected from the initially large library, shows that over 20% of this population is thrombin-resistant, likely due to folding. Analysis of the amino acid sequences of these clones shows no significant homology to extant proteins, which indicates that they are indeed totally de novo. A few of these sequences have been expressed, and here we describe the structural properties of two thrombin-resistant randomly selected ones. These two de novo proteins have been characterized by spectroscopic methods and, in particular, by circular dichroism. The data show a stable three-dimensional folding, which is temperature-resistant and can be reversibly denatured by urea. The consequences of this finding within a library of 'Never Born Proteins' are discussed in terms of molecular evolution.


Synergetic role of integrating the departments of cancer registry and clinical research at an academic comprehensive cancer center.
Integration of the cancer registry and clinical research departments can have a significant impact on the accreditation process of a Commission on Cancer (CoC) Program. Here in we demonstrate that the integration of both departments will benefit as there is increased knowledge, manpower and crossover in job responsibilities in our CoC-accredited Academic Comprehensive Cancer Center. In our model this integration has led to a more successful cooperative interaction among departments, which has in turn created an enhanced combined effect on overall output and productivity. More manpower for the cancer registry has led to increased caseloads, decreased time from date of first contact to abstraction, quality of data submissions, and timely follow-up of all patients from our reference date for accurate survival analysis along with completeness of data. In 2016, our Annual Facility report showed an additional 163 cases over prediction by the state of Maryland Cancer Registry and a 39% increase in case completeness. As proof of the synergetic effectiveness of our model within one year of its implementation, the cancer center was able to apply for, and was awarded membership from Alliance for Clinical Trials in Oncology, Central IRB, and in turn led to increased clinical trial accrual from 2.8% in 2014 compared to 13.2% currently. Our cancer registry in year one submitted over 150 more cases than predicted, improved quality outcome measures displayed by our Cancer Program Practice Profile reports and had more timely and complete data submissions to national and state registries. This synergetic integration has led to a better understanding, utilization and analysis of data by an integrated team with Clinical Research expertise.


Nicotinic acetylcholine receptors in a songbird brain.
Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that mediate fast synaptic transmission and cell signaling, which contribute to learning, memory, and the execution of motor skills. Birdsong is a complex learned motor skill in songbirds. Although the existence of 15 nAChR subunits has been predicted in the avian genome, their expression patterns and potential contributions to song learning and production have not been comprehensively investigated. Here, we cloned all the 15 nAChR subunits (ChrnA1-10, B2-4, D, and G) from the zebra finch brain and investigated the mRNA expression patterns in the neural pathways responsible for the learning and production of birdsong during a critical period of song learning. Although there were no detectable hybridization signals for ChrnA1, A6, A9, and A10, the other 11 nAChR subunits were uniquely expressed in one or more major subdivisions in the song nuclei of the songbird brain. Of these 11 subunits, ChrnA3-5, A7, and B2 were differentially regulated in the song nuclei compared with the surrounding anatomically related regions. ChrnA5 was upregulated during the critical period of song learning in the lateral magnocellular nucleus of the anterior nidopallium. Furthermore, single-cell RNA sequencing revealed ChrnA7 and B2 to be the major subunits expressed in neurons of the vocal motor nuclei HVC and robust nucleus of the arcopallium, indicating the potential existence of ChrnA7-homomeric and ChrnB2-heteromeric nAChRs in limited cell populations. These results suggest that relatively limited types of nAChR subunits provide functional contributions to song learning and production in songbirds.


Comment on "Dynamic properties in a family of competitive growing models".
The article [Phys. Rev. E 73, 031111 (2006)] by Horowitz and Albano reports on simulations of competitive surface-growth models RD+X that combine random deposition (RD) with another deposition X that occurs with probability p . The claim is made that at saturation the surface width w(p) obeys a power-law scaling w(p) proportional, variant1/pdelta, where delta is only either delta=1/2 or delta=1 , which is illustrated by the models where X is ballistic deposition and where X is RD with surface relaxation. Another claim is that in the limit p-->0+, for any lattice size L, the time evolution of w(t) generally obeys the scaling w(p,t) proportional, variant(Lalpha/pdelta)F(p2deltat/Lz), where F is Family-Vicsek universal scaling function. We show that these claims are incorrect.


Cytomegalovirus infection of the alimentary canal: radiologic findings with pathologic correlation.
A spectrum of radiologic findings in cytomegalovirus (CMV) infection of the alimentary canal seen in 14 patients and correlated with pathologic examinations is described. Twelve patients had acquired immunodeficiency syndrome and two had no identified immunosuppression. Autopsies were performed on 12. Diffuse CMV colitis was present in eight patients, enteritis in seven, esophagitis in four, gastritis in two, cholangitis in one, and acute pancreatitis in one. Of 11 patients with enteritis and/or colitis seven had significant lower gastrointestinal bleeding and five died as a result of it. Radiologic findings in the gastrointestinal tract included superficial or deep mucosal ulcerations, perforation or fistula formation, luminal narrowing, rigidity and thickening of the intestinal wall, and inflammatory infiltration of the mesentery. These were seen on barium examinations and computed tomographic (CT) scans. Findings of pancreatitis were seen on CT scans in one patient. In another, a cholangiogram showed abnormal bile ducts caused by CMV cholangitis. The radiologist should be aware of the diverse manifestations of the disease and its likely occurrence in immunosuppressed individuals.


The essential nucleolar yeast protein Nop8p controls the exosome function during 60S ribosomal subunit maturation.
The yeast nucleolar protein Nop8p has previously been shown to interact with Nip7p and to be required for 60S ribosomal subunit formation. Although depletion of Nop8p in yeast cells leads to premature degradation of rRNAs, the biochemical mechanism responsible for this phenotype is still not known. In this work, we show that the Nop8p amino-terminal region mediates interaction with the 5.8S rRNA, while its carboxyl-terminal portion interacts with Nip7p and can partially complement the growth defect of the conditional mutant strain Δnop8/GAL::NOP8. Interestingly, Nop8p mediates association of Nip7p to pre-ribosomal particles. Nop8p also interacts with the exosome subunit Rrp6p and inhibits the complex activity in vitro, suggesting that the decrease in 60S ribosomal subunit levels detected upon depletion of Nop8p may result from degradation of pre-rRNAs by the exosome. These results strongly indicate that Nop8p may control the exosome function during pre-rRNA processing.


Persistent median artery in the hand: a report with a brief review of the literature.
We encountered a persistent median artery in the forearms and hands bilaterally in a 78-year-old Japanese male cadaver during dissection practice at Wakayama Medical University. The brachial arteries divided into the ulnar and radial arteries. The ulnar artery gave off the median and posterior interosseous arteries at the same point, although the anterior interosseous artery was not found. The median artery ran along the median nerve and bifurcated in the hand. In the superficial layer of the palm, one branch of the median artery ran to the ulnar side of the thumb, whereas the other passed to the second interdigital space. The ulnar artery reached the third and fourth interdigital spaces and the ulnar side of the little finger, and showed no anastomosis with the median artery in the superficial layer of the palm. The radial artery did not give off the superficial palmar branch. Therefore, the formation of the superficial palmar arch was incomplete. In the deep layer of the palm, the radial artery formed the deep palmar arch with the deep palmar branch of the ulnar artery and gave off the princeps pollicis artery. In the dorsum of hand, the radial artery passed over the first dorsal interosseous muscle to the index finger and communicated with the palmar pollical artery from the median artery in the first interosseous space. The present study reports an unusual variation of the persistent median artery in the hand and briefly reviews the literature about the median artery.


Data demonstrating distinct embryonic developmental defects induced by bisphenol a alternatives.
Embryos of Xenopus laevis (African clawed frog) were exposed to the widespread environmental plasticizers bisphenol AF (BPAF; 0.003-3 μM), bisphenol A (BPA; 1-50 μM), or 17β-estradiol (E2; 10 μM) from just after fertilization through 96 hours of development. The potencies and cellular and morphological effects were compared across chemical treatments and controls. The embryos were staged, counted and imaged, and time-lapse movies collected, on an inverted stereomicroscope and camera. The data show there were both shared and unique effects of BPAF, BPA, and E2, on early cleavage divisions and development of the spinal cord, head, and gut, with BPAF having the greatest potency and toxicity (1000 times more potent than BPA). Specifically, cleavage divisions, within 1-6 hours of exposure had severe irregularities including asymmetrical division, slowed mitosis and cytokinesis, cellular dissociation, and fewer numbers of cells per embryo. By 48 hours of exposure the embryos had curved body axis defects, neural tube defects including curved, incomplete, or two neural tubes, ventral and gut blisters, and overall extreme abnormalities. By 96 hours of exposure estradiol caused tail flexures/bent spines, severe pigmentation reduction, long loosely coiled gut, and a ventral blister in 100% of embryos. BPA caused truncated body axis defects, tail flexures, and head and eye malformations in over 60% of embryos. BPAF, at the lowest doses tested, caused craniofacial defects, shorter tails, ventral blisters, edema and peritoneal effusion in over 75% of the surviving embryos. For a complete description, interpretation of the data and a discussion refer to the article in press Arancio et al., 2018.


High DRC Levels Are Associated with Let-7b Overexpression in Women with Breast Cancer.
Nucleotide Excision Repair (NER) is a critical pathway involved in breast cancer (BC). We have previously published that a low DNA repair capacity (DRC) is associated with a higher risk of BC in Puerto Rican women. Let-7b belongs to a miRNA family with tumor suppressor activity that targets oncogenes. We isolated miRNAs from plasma of 153 Puerto Rican women with and without BC. DRC was measured in lymphocytes by means of a host cell reactivation assay. These women were divided into four groups according to their DRC level: High (>3.8%) and low (<3.8%). The four groups consisted of BC patients with high (n = 35) and low (n = 43) DRC and controls with high (n = 39) and low (n = 36) DRC. Epidemiologic data were collected at initial BC diagnosis and almost five years after diagnosis. A significant difference in Let-7b expression was found in BC patients with high DRC versus the remaining groups (p < 0.001). Thus, our data reveal a possible role of Let-7b on DRC during breast carcinogenesis. Our study is innovative because it provides the first evidence that Let-7b may play role in DRC regulation (through the NER repair pathway) in BC.


Neoadjuvant Chemotherapy Reduces the Treatment-free Interval After First-line Treatment in Patients With Advanced Ovarian Cancer.
The aim of the study was to compare platinum resistance and treatment-free interval (TFI) following treatment with neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) or primary debulking surgery (PDS) in women with advanced epithelial ovarian cancer (EOC). The study included patients diagnosed with primary EOC, stage IIIC or IV, between 2005 and 2013. Patients were grouped according to first-line treatment (PDS vs. NACT-IDS). Date of second-line treatment initiation was used to evaluate platinum sensitivity. The study population included 521 patients, of which 371 (71%) and 150 (29%) underwent PDS and NACT-IDS, respectively. We found no difference in platinum resistance between groups. Platinum-sensitive patients treated with NACT-IDS had a shorter median TFI (372 vs. 497 days, p=0.042). Similarly, patients with no residual tumor after IDS had a shorter median TFI (280 vs. 302 days, p=0.005). NACT-IDS may shorten the TFI after first-line platinum-based chemotherapy.


Population-level analyses indirectly reveal cryptic sex and life history traits of Pseudoperkinsus tapetis (Ichthyosporea, Opisthokonta): a unicellular relative of the animals.
We use population genetics to detect the molecular footprint of a sexual cycle, of a haploid vegetative state, and of lack of host specificity in Pseudoperkinsus tapetis, a marine unicellular relative of the animals. Prior to this study, complete life cycles were not known for any of the unicellular lineages sharing common ancestry with multicellular animals and fungi. We established the first collection of conspecific cultures of any member from the unicellular opisthokont lineage ichthyosporea, isolating 126 cultures of P. tapetis from guts of marine invertebrates ranging from clams to sea cucumbers. We sequenced fragments of the elongation factor alpha-like (EFL) and heat-shock protein 70 (HSP70) genes for a subset of our isolates. Absence of heterozygotes from the EFL locus in 52 isolates provided evidence for haploidy. Phylogenetic incongruence and a lack of support for linkage between two loci from 34 sequenced isolates signified a history of recombination consistent with a sexual cycle. Shared haplotypes in different invertebrate species showed that P. tapetis was not host specific. Based on estimates of the frequency of sex and on observations of cultures, we propose that P. tapetis is transmitted between hosts via asexual endospores. New protists are continually being discovered, and, as this study illustrates, analysis of culturable collections from natural habitats can transform a species from a near unknown to a model system for better understanding the evolution of life histories.


Lymphocyte homing receptor (CD44) expression is associated with poor prognosis in gastrointestinal lymphoma.
Lymphocyte homing receptor (CD44) is involved in lymphocyte adhesion to endothelial cells of high endothelial venules (HEVs) and lymphocyte exit from the blood circulation, and it may be involved also in hematogenous dissemination of malignant lymphoma. Prognostic significance of lymphocyte homing receptor expression defined by Hermes-3 antibody was studied among 27 gastrointestinal lymphomas followed up for 8 to 20 years after the diagnosis. Lymphomas lacking or with very weak homing receptor expression (n = 14, 52%) were associated with 57% 10-year survival rate as compared with only 15% among lymphomas that expressed CD44 more strongly (P = 0.02). We conclude that lack of lymphocyte homing receptor expression is common in gastrointestinal lymphoma, and that CD44 expression is associated with unfavourable prognosis.


High-level gentamicin-resistant and vancomycin-resistant Enterococcus faecium isolated from a wound in a dog.
This report describes the first clinical case, in Europe, of a high-level gentamicin-resistant and vancomycin-resistant Enterococcus faecium infection in a dog. The aim of this report is to alert the veterinary profession to high-level gentamicin-resistant and vancomycin-resistant Enterococcus faecium in companion animal patients. Multi-drug resistant strains of this pathogen are the cause of considerable problems in human hospitals and for community healthcare professionals worldwide. The potential for a similar impact within veterinary medicine is discussed.


Blast resistance in Indian rice landraces: Genetic dissection by gene specific markers.
Understanding of genetic diversity is important to explore existing gene in any crop breeding program. Most of the diversity preserved in the landraces which are well-known reservoirs of important traits for biotic and abiotic stresses. In the present study, the genetic diversity at twenty-four most significant blast resistance gene loci using twenty-eight gene specific markers were investigated in landraces originated from nine diverse rice ecologies of India. Based on phenotypic evaluation, landraces were classified into three distinct groups: highly resistant (21), moderately resistant (70) and susceptible (70). The landraces harbour a range of five to nineteen genes representing blast resistance allele with the frequency varied from 4.96% to 100%. The cluster analysis grouped entire 161 landraces into two major groups. Population structure along with other parameters was also analyzed to understand the evolution of blast resistance gene in rice. The population structure analysis and principal coordinate analysis classified the landraces into two sub-populations. Analysis of molecular variance showed maximum (93%) diversity within the population and least (7%) between populations. Five markers viz; K3957, Pikh, Pi2-i, RM212and RM302 were strongly associated with blast disease with the phenotypic variance of 1.4% to 7.6%. These resistant landraces will serve as a valuable genetic resource for future genomic studies, host-pathogen interaction, identification of novel R genes and rice improvement strategies.


Beyond Pneumonia: A Rare Case of Pericardial Empyema Caused by Streptococcus pneumoniae.
Purulent pericardial effusion is a rare but potentially deadly condition that demands immediate medical attention. When left untreated, it can have catastrophic consequences. While bacterial infection is the most common cause of this condition, it usually occurs in individuals with weakened immune systems or in those undergoing dialysis or thoracic surgery. This case report presented here is unique as it chronicles the uncommon experience of a 58-year-old male with a normally functioning immune system who suffered from purulent pericardial effusion, endocarditis, and pneumonia, all linked to septic arthritis of his knee caused by Streptococcus pneumoniae. The diagnosis and management of this condition require a swift and comprehensive approach, and any delay in treatment can have dire outcomes. This case highlights the significance of early detection and prompt treatment of purulent pericardial effusion to prevent severe complications and improve patient prognosis.


Ca2+ sensitivity of regulated cardiac thin filament sliding does not depend on myosin isoform.
Myosin heavy chain (MHC) isoforms in vertebrate striated muscles are distinguished functionally by differences in chemomechanical kinetics. These kinetic differences may influence the cross-bridge-dependent co-operativity of thin filament Ca(2+) activation. To determine whether Ca(2+) sensitivity of unloaded thin filament sliding depends upon MHC isoform kinetics, we performed in vitro motility assays with rabbit skeletal heavy meromyosin (rsHMM) or porcine cardiac myosin (pcMyosin). Regulated thin filaments were reconstituted with recombinant human cardiac troponin (rhcTn) and alpha-tropomyosin (rhcTm) expressed in Escherichia coli. All three subunits of rhcTn were coexpressed as a functional complex using a novel construct with a glutathione S-transferase (GST) affinity tag at the N-terminus of human cardiac troponin T (hcTnT) and an intervening tobacco etch virus (TEV) protease site that allows purification of rhcTn without denaturation, and removal of the GST tag without proteolysis of rhcTn subunits. Use of this highly purified rhcTn in our motility studies resulted in a clear definition of the regulated motility profile for both fast and slow MHC isoforms. Maximum sliding speed (pCa 5) of regulated thin filaments was roughly fivefold faster with rsHMM compared with pcMyosin, although speed was increased by 1.6- to 1.9-fold for regulated over unregulated actin with both MHC isoforms. The Ca(2+) sensitivity of regulated thin filament sliding speed was unaffected by MHC isoform. Our motility results suggest that the cellular changes in isoform expression that result in regulation of myosin kinetics can occur independently of changes that influence thin filament Ca(2+) sensitivity.