Spatial quantification and classification of skin response following perturbation using organotypic skin cultures.
For a mechanistic understanding of skin and its response to an induced perturbation, systems biology is gaining increasing attention. Unfortunately, quantitative and spatial expression data for skin, like for most other tissues, are almost not available. Integrating organotypic skin cultures, whole-slide scanning and subsequent image processing provides bioinformatics with a novel source of spatial expression data. We here used this approach to quantitatively describe the effect of treating organotypic skin cultures with sodium dodecyl sulphate in a non-corrosive concentration. We first measured the differentiation-related spatial expression gradient of Heat-Shock-Protein 27 in a time series of up to 24 h. Secondly, a multi-dimensional tissue classifier for predicting skin irritation was developed based on abstract features of these profiles. We obtained a high specificity of 0.94 and a sensitivity of 0.92 compared with manual classification. Our results demonstrate that the integration of tissue cultures, whole-slide scanning and image processing is well suited for both the standardized data acquisition for systems biological tissue models and a highly robust classification of tissue responses.


Targeted and systemic insights into the crosstalk between DNA-dependent protein kinase catalytic subunit and receptors of estrogen, progesterone and epidermal growth factor in the context of cancer.
DNA-dependent protein kinase catalytic subunit (DNA-PKcs) has emerged as a regulator of carcinogenesis. Increased expression of DNA-PKcs correlates with metastatic cancers. Here we review recently reported crosstalk of DNA-PKcs with estrogen (ER), progesterone (PR) and epidermal growth factor (EGFR) receptors. The reports show an extensive network of functional and direct interactions. Targeted studies focused on specific molecular mechanisms, and a systems biology network analysis shows unbiasedly engagement of various cellular functions. Feedforward regulation between expression and activities of DNA-PKcs and ER, DNA-PKcs-dependent phosphorylation of PR and an impact on PR-dependent transcription, and DNA-PKcs-promoted EGFR-dependent aggressiveness and metastases are examples of the results of targeted studies. Systems biology approach extracted many more genes and proteins engaged by DNA-PKcs in interaction with ER, PR, and EGFR. Examples are such regulators and predictors of breast tumorigenesis as BRCA1, TP53, and 18 genes of the MammaPrint signature. Reviewed here data suggest that the diagnostic value of DNA-PKcs in the context of ER, PR and EGFR signaling is defined by a network signature rather than by single markers. This review summarizes mechanisms of DNA-PKcs interaction with ER, PR, and EGFR, highlights tumor suppressors and oncogenes engaged by DNA-PKcs, and emphasizes the importance of diagnostic network-based signatures.


Population variability in CD38 activity: correlation with age and significant effect of TNF-α -308G>A and CD38 184C>G SNPs.
CD38 (EC 184.108.40.206, NAD(+)-glycohydrolase) is a multifunctional enzyme catalyzing the synthesis and hydrolysis of cyclic ADP-ribose from NAD(+) to ADP-ribose. The loss of CD38 function is associated with impaired immune responses, metabolic disturbances, and behavioral modifications. Notably, it has been linked to HIV infection, leukemias, myelomas, solid tumors, Type II Diabetes mellitus, bone metabolism, as well as Autism Spectrum Disorder. Taking into account the crucial role played by CD38 in many diseases and in clinical practice, here we assessed the distribution of CD38 NADase activity in a healthy population (104 sex-matched unrelated individuals, 12-98 years) and determined its main predictors among genetic and physiological factors (age and sex). The mean value of CD38 NADase activity was 0.051±0.023 mU/mg (0.010-0.099 mU/mg), following a normal distribution in the study population (Kolmogorov-Smirnov test P=0.200). The TNF-α -308G>A (rs1800629) resulted the main predictor (β=0.364, P=0.00008), followed by Age (β=0.280, P=0.002) and the CD38 184C>G (rs6449182) (β=0.193, P=0.033). Our study contributes to understanding CD38 enzyme physiological functions, by reporting, for the first time, its activity distribution in healthy individuals and demonstrating a significant positive correlation with age. Moreover, the possible use of TNF-α -308G>A (rs1800629) and the CD38 184C>G (rs6449182) SNPs as predictive genetic markers of CD38 activity, clearly point toward possible pharmacogenomic applications and to a more refined use of CD38 in clinical settings.


Evaluating hormone therapy-associated increases in breast density comparison between reported and simultaneous assignment of BI-RADS categories, visual assessment, and quantitative analysis.
Changes in breast density, which are commonly associated with hormone replacement therapy (HRT) use, may imply changes in breast cancer risk. This study explores the ability of different methods to detect hormone replacement therapy (HRT)-associated increases in breast density. Between 1997 and 2001, 51 postmenopausal women were reported to have HRT-associated increases in breast density at our institution. Twenty postmenopausal women not reported to have an increase in density during the same period were selected as controls. Mammograms from date of report and earlier comparison were used. Breast Imaging Reporting and Data System (BI-RADS) density categories from both dates were obtained from the mammography report. Mammograms were reviewed at separate time points and density changes evaluated by assigning BI-RADS density categories, visual assessment, and computer-assisted quantitative analysis. Mammogram reports were not available for two patients. The remaining 49 women with reported HRT increases in density were included. Reported BI-RADS categories resulted in detection of 57%, simultaneous BI-RADS assignment in 61%, visual assessment in 100%, and quantitative assessment in 94% of women with HRT-associated increases in density. Reported BI-RADS category change was the only method that resulted in false-positive increases in density for control patients. Minimal HRT associated increases in density were the most difficult to detect, with 90% of these 21 cases not detected by simultaneous BI-RADS category assignment and 3 cases not detected by quantitative methods when defined as an increase of at least 5%. Visual and quantitative assessment best identified women with HRT-associated increases in density, including those with minimal increases. Simultaneous assignment of BI-RADS categories was considerably better than use of reported BI-RADS categories. This information may be helpful in guiding research design of studies evaluating changes in density from the HRT use.


Expression and regulation of the chemokine CXCL16 in Crohn's disease and models of intestinal inflammation.
CXCL16 mediates adhesion and phagocytosis of both Gram-negative and Gram-positive bacteria and is a strong chemoattractant for CXCR6+ T cells. In this study, we determined the so far unknown expression and signal transduction of the novel CXCL16-CXCR6 chemokine-ligand receptor system in intestinal inflammation in vivo and in vitro. CXCL16 mRNA was measured by quantitative PCR in human colonic biopsies of patients with Crohn's disease (CD) as well as in the TNFΔARE mouse model of ileitis and in murine cytomegalovirus (MCMV)-induced colitis. CXCL16 serum levels were analyzed by ELISA. CXCL16-induced signal transduction was analyzed in intestinal epithelial cells with phospho-specific antibodies for mitogen-activated protein (MAP) kinases and Akt. We found an inverse expression pattern of CXCL16 and CXCR6, with highest CXCL16 mRNA expression in the proximal murine small intestine and the highest CXCR6 mRNA expression in the distal colon. CXCL16 and CXCR6 mRNA were expressed in colorectal cancer (CRC)-derived intestinal epithelial cell (IEC) lines. CRC-expressed CXCR6 was functional, as demonstrated by CXCL16-induced MAP kinase and Akt activation. Intestinal CXCL16 expression was elevated in the TNFΔARE mouse model of ileitis and in MCMV-induced colitis (P < 0.05) and in the sera and colons of patients with CD (P < 0.05), where its expression correlated highly with CXCR6 and IL-8 levels (r = 0.85 and 0.89, respectively). CRC-derived IECs express the functional CXCL16 receptor CXCR6. CXCL16 mRNA and protein expression is up-regulated in intestinal inflammation in vitro and in CD patients, suggesting an important role for this chemokine in intestinal inflammation.


Nursing student and faculty perceptions of reciprocity during international clinical learning experiences: A qualitative descriptive study.
Exposure of nursing students to global health care systems and cultures that are vastly different from which they are accustomed allow them to gain a unique perspective of our global village. A plethora of research has studied the lived experiences of visiting students during international clinical placements. Many studies have noted a multitude of benefits for visiting students. However, very little research examined the perspectives of host participants. This study explores both visiting and host students and faculty's perceptions of reciprocity during international learning experiences. A qualitative descriptive design was utilised. Intercultural collaboration between visiting and host participants occurred over a two week clinical learning experience in a regional hospital in Jamaica. Ten third year undergraduate Bachelor of Nursing students and two faculty from Canada engaged in clinical learning experiences with twelve fourth year host nursing students and three faculty from Jamaica. Visiting students submitted reflective papers, participated in interviews, and a focus group two months later. Two separate focus groups were held to gather data from the hosting students and faculty. All data was analysed using thematic analysis for recurring themes. The findings of this study show that both host and visiting students and faculty mutually gain benefits from intercultural exchange and collaboration. Reciprocity was noted in experiential knowledge acquisition, cultural awareness from educational and professional perspectives, and personal and professional transformative learning. Although notable differences from contrasting health care worlds were identified, the recognition of similarities and opportunities for transformative learning greatly outweighed the differences. There are reciprocal benefits to be gained in nursing education for visiting and host participants through the development of collaborative international partnerships. More research is required to further explore mutuality for students and faculty from different countries.


HER2 mediates clinical resistance to the KRASG12C inhibitor sotorasib, which is overcome by co-targeting SHP2.
Mutant RAS guanosine triphosphate hydrolases (GTPases) are key oncogenic drivers in many cancers. The KRASG12C variant has recently become targetable by a new drug class specifically locking KRASG12C in its inactive guanosine diphosphate (GDP)-bound state. Clinical activity was demonstrated in patients with advanced lung cancers harbouring KRASG12C mutations but was limited by the development of resistance. A biopsy from progressing lung cancer of a patient treated with the KRASG12C inhibitor sotorasib was obtained, and the underlying resistance factors were analysed. Mechanistic studies were performed in vitro and in vivo to uncover strategies to overcome resistance to KRASG12C inhibition. We demonstrated acquisition of HER2 copy number gain and KRASG12C mutation retention in the post-progression biopsy. To explore HER2 gain as the relevant resistance mechanism, we generated KRASG12C lung cancer models overexpressing HER2. MAPK pathway signalling remained active despite KRASG12C inhibitor treatment. Combined pharmacological inhibition of KRASG12C and SHP2 synergistically overcame HER2-mediated resistance in vitro and in vivo. These findings establish HER2 copy number gain as a clinically relevant mechanism of resistance to pharmacological KRASG12C inhibition that can be overcome by co-targeting SHP2.


Visual evaluation of cattle cleanliness and correlation to carcass microbial contamination during slaughtering.
The aim of the study was to establish whether the visual cleanliness of cattle slaughtered was correlated to hide and carcass contamination as indicated by aerobic colony count (ACC), Enterobacteriaceae count (EC) and Escherichia coli count (ECC). Cattle in a slaughterhouse were visually inspected and assigned to a category from 1 (very clean) to 5 (very dirty) based on cleanliness. Fifteen animals for each category were randomly selected, hide and carcass sampled and analyzed for ACC, EC and ECC. Results showed that increasing dirt on cattle was associated with higher ACC, EC and ECC on hide and carcasses. Carcass ACC and ECC belonging to animals classified in cleanliness categories 3, 4 or 5 have a higher probability of exceeding the limits set by the Reg. EU 2073/2005. The study supports the conclusion that the pre-slaughter visual evaluation of animal cleanliness and application of corrective actions can be an effective aid to reduce carcass contamination.


Seeds in droppings of tropical fruit-eating birds: importance of considering seed composition.
The probability of interspecific seedling competition from bird droppings is high because fruit-eating birds, on average, deposit more than two species in a single dropping. Moreover, birds vary both in the number of plant species they deposit in a given dropping and in the seed composition of those droppings. In a preliminary experiment, I examined effects of interspecific seedling competition from seeds found in bird droppings. Certain plant species were competitively superior in pairwise growth experiments using six common second-growth species. The survival of certain shrubs depended on which species it was disseminated with in bird droppings. Rapid germination time may promote competitive superiority in some cases. Birds affect plant fitness not only because of their behavior following dispersal, but also because they deposit seeds in different densities and combinations.


Suitability for psychoanalytic psychotherapy: a review.
To review empirical studies on outpatients' pretherapy suitability for psychoanalytic psychotherapy. A literature search for studies in English was made in the databases MEDLINE, PsychInfo and EM-base. Forty-one studies spanning 20 years were selected for a thorough evaluation. Seventy-five per cent of the studies concerned brief dynamic psychotherapy. In general, application of single measures of suitability had a modest predictive value with correlations in the range of 0.17-0.73. There was no consistent difference between various formats of therapies. Most promising variables with the highest correlations with good outcome were: 'good quality of object relations', 'psychological mindedness' and 'motivation for change'. Some clinical guidelines can be drawn from quantitative research to provide the therapist with best method and format. The importance of psychological variables known from the development of the brief dynamic therapies and earlier research was confirmed. Most correlations were modest and single factors could not be identified. Multivariate designs that combine different methods and formats with patient characteristics seem most promising in future predictor-outcome research.


Pertussis toxin sensitivity of drug-induced potentials on the rat superior cervical ganglion.
We have investigated the action of pertussis toxin on a range of receptor-mediated responses of the rat superior cervical ganglion in vitro. The ganglia were treated with pertussis toxin for 24 h at 37 degrees C using an in vitro method. Appropriate controls were also carried out. Pertussis toxin (1 microgram/ml) reduced ganglionic hyperpolarisations mediated by adenosine, alpha 2, 5-HT1A, M2 and GABAB receptors. The GABAB-mediated hyperpolarisation of this preparation, evoked by baclofen and GABA in a bicuculline-resistant manner, has not previously been reported. Pertussis toxin did not reduce ganglionic depolarisations evoked by potassium chloride and 5-HT3, GABAA and nicotinic receptors. Depolarisations to muscarine and noradrenaline, probably mediated by M1 and beta-receptors, also appeared to be resistant to pertussis toxin. The similar sensitivity of the various ganglionic hyperpolarisations to pertussis toxin indicates that they may all be mediated by similar G-proteins.


MicroRNA-101 suppresses motility of bladder cancer cells by targeting c-Met.
MicroRNAs (miRNAs) are small non-coding RNAs that play regulatory roles by repressing translation or cleaving RNA transcripts. Here, we report that the expression of microRNA-101 (miR-101) is down-regulated in human bladder cancer tissue versus normal adjacent tissue. To better characterize the role of miR-101 in bladder cancer, we conducted a gain-of-function analysis by transfecting the bladder cancer cell line T24 with chemically synthesized miR-101 mimics. We found that miR-101 directly targets c-Met via its 3'-UTR. Specifically, forced expression of miR-101 decreased c-Met expression at both mRNA and protein levels, consequently inhibiting T24 cell migration and invasion in a c-Met-dependent manner. In conclusion, we have shown miR-101 to be a novel suppressor of T24 cell migration and invasion through its negative regulation of c-Met.


Intraoperative flap complications in laser in situ keratomileusis with two types of microkeratomes.
To determine the incidence and types of intraoperative flap complications in laser in situ keratomileusis (LASIK) encountered with the Hansatome microkeratome and the Moria microkeratome. In this retrospective case series, all patients with intraoperative flap complications who were treated between June 1999 and July 2008 at the Eye Consultants Center in Riyadh, Saudi Arabia, were identified and reviewed. Of the 4352 subjects who underwent bilateral primary LASIK procedure, intraoperative microkeratome complications were detected in 89 eyes of 83 patients. The overall incidence of flap complications was 89/8704 (1.00%): incomplete flaps occurred in 53 eyes (0.60%), followed by buttonhole flaps in 17 eyes (0.19%), free complete flaps in 10 eyes (0.11%), free partial flaps in 6 eyes (0.07%), sluffed epithelium in 2 eyes (0.023%), and a splitted flap (vertical flap cut) in 1 eye (0.01%). The incidence rates of intraoperative flap complications with the Hansatome microkeratome and the Moria microkeratome were 1.21% (41/3378) and 0.90% (48/5326), respectively (P = 0.19). There was a statistically significant difference between the two microkeratomes with regard to the incidence of buttonhole flaps: 0.33% (11/3378) for the Hansatome microkeratome versus 0.11% (6/5326) for the Moria microkeratome (P = 0.04). Generally, the incidence rates of intraoperative flap complications with the Hansatome microkeratome and the Moria microkeratome were similar. However, buttonhole flaps occurred more often with the Hansatome microkeratome (a type of microkeratome that produces larger flaps). The commonest complication encountered was the incomplete flap, followed by the buttonhole flap and free flap.


Translocation D/D involving two homologous chromosomes of the pair 15.
A translocation between two homologues of chromosomes 15 was identified in a phenotypically normal female with the R-banding technique. The C-banding technique demonstrated an abnormally large band on the translocation chromosome. This finding suggests a possibility that the translocation might be due to breaks in the short arms or to fusion at telomeric ends. The patient had four spontaneous abortions and no normal pregnancy.


Size matters, so does shape: Inhibition of transcription of T7 RNA polymerase by iron(II) clathrochelates.
Coordination and organoelement compounds are rarely proposed as the drug candidates despite their vast potential in the area owing to their strictly controlled geometry and rather extensive surface. This is the first example of the inhibition of transcription in the system of T7 RNA polymerase by cage metal complexes. Their IC50 values reach as low as the nanomolar range, placing them among the most potent metal-based transcription inhibitors.


Repair of the sublethal and mutational damage induced by x-rays in Chinese hamster HAI cells in vitro.
The ability of Chinese hamster hai cells to repair damage related to cell death and mutational change induced by X-rays were examined by using a sensitive forward mutation system from prototrophic CH-hai Cl 23 cells to auxotrophs. The results obtained from the split dose experiments seem to suggest that Chinese hamster hai cells have the repair mechanisms for the sublethal and mutational damage induced by X-rays and that the repair mechanisms act in common for the repair of both cases of damage.


Gamete formation via meiotic nuclear restitution generates fertile amphiploid F1 (oat×maize) plants.
Hybrid (oat×maize) zygotes developed into euhaploid plants with complete oat chromosome complements without maize chromosomes and into aneuhaploid plants with complete oat chromosome complements and different numbers of retained individual maize chromosomes. The elimination of maize chromosomes in the hybrid embryo is caused by uniparental genome loss during early steps of embryogenesis. Some of these haploid plants set seed in up to 50% of their self-pollinated spikelets. The high fertility was found to be mainly caused by formation of numerically unreduced female and male gametes (nunreduced=3x+0…3=21…24 chromosomes). Gamete formation involves meiotic nuclear restitution. The restitution process is caused by an alternative type of meiosis. It follows the model of levigatum-type semi-heterotypic divisions, but with a formation of the nuclear membrane at the transition from telophase I to interkinesis, which resembles the model of pygaera-type pseudo-homotypic divisions. We propose the name haploid meiotic restitution for this particular process combination. We discuss the use and implications of the specific process of gamete formation in F1 (oat×maize) plants.


Development of the rat thalamus: VI. The posterior lobule of the thalamic neuroepithelium and the time and site of origin and settling pattern of neurons of the lateral geniculate and lateral posterior nuclei.
Short-survival, sequential, and long-survival thymidine radiograms of rat embryos, fetuses, and young pups were analyzed in order to determine the time of origin, site of origin, migratory route, and settling pattern of neurons of the dorsal lateral geniculate (LGD), ventral lateral geniculate (LGV), and lateral posterior (LP) nuclei of the thalamus. Quantitative examination of long-survival radiograms established that the neurons of the LGD are produced on days E14 and E15. Within the LGD there is an external-to-internal neurogenetic gradient; the majority (77%) of neurons of the external half are generated on day E14, while in the internal half the majority (64%) of neurons originate on day E15. The late-generated LGD neurons are located in the termination field of the uncrossed fibers of the optic tract. Examination of short-survival radiograms indicated that the neurons of the LGD originate in a discrete neuroepithelial eversion situated ventral to the pineal rudiment and dorsal to the putative neuroepithelium of the ventral nuclear complex. In sequential radiograms from rats injected with 3H-thymidine on day E15 and killed on days E16 and E17, the migration of young LGD neurons was followed in a posterolateral direction to the formative lateral geniculate body. By day E17, the day when the optic tract fibers begin to disperse over the lateral surface of the posterior diencephalon, the distribution of early and late-generated neurons of the LGD resembles that seen in young pups. As a whole, the neurons of the LGV are produced earlier than the neurons of the LGD. The bulk of LGV neurons are generated on days E14 and E15 in a caudal-to-rostral intranuclear neurogenetic gradient. Caudal LGV neurons are generated mainly on day E14 (82%), while a substantial proportion of rostral neurons (32%) are generated on day E15. Examination of short-survival and sequential radiograms suggest that the LGV neurons originate in an inverted sublobule situated beneath the putative neuroepithelium of the LGD. At anterior levels the putative inverted sublobule of the LGV merges imperceptibly with the neuroepithelium that produces the neurons of the lateral habenular nucleus. Like the neurons of the LGD and LGV, so also those of the LP are generated on days E14 and E15, but the neurogenetic gradients are different. There is a lateral-to-medial gradient within the LP as a whole. Peak production of neurons is on day E14 laterally (58%) and on day E15 medially (59%).(ABSTRACT TRUNCATED AT 400 WORDS)


Phosphorylation of solubilized sarcoplasmic reticulum by orthophosphate and its thermodynamic characteristics. The dominant role of entropy in the phosphorylation.
A large fraction of the Ca-2plus- and Mg-2plus-dependent ATPase (EC 188.8.131.52) in sarcoplasmic reticulum membranes solubilized with Triton X-100 was phosphorylated with Pi. The phosphorylation required Mg-2plus but was strongly inhibited by low concentrations of Ca-2plus. A Ca-2plus ion concentration of 30 muM caused half-maximum inhibition in the presence of 50 mM MgCl2. The phosphorylated enzyme showed a rapid turnover and was in dynamic equilibrium with Pi in the medium. At equilibrium the amount of the phosphorylated enzyme increased markedly with increased in the reaction temperature. The apparent standard free energy change, the apparent standard enthalpy change, and the apparent standard entropy change in the formation of the phosphorylated enzyme from the enzyme-phosphate complex in the presence of excess Mg-2plus at 37 degrees and pH 7.0 were, respectively, 0.35 Cal per mol, 15.9 Cal per mol, and 50.2 e.u. per mol. The susceptibility of the acid-denatured phosphorylated enzyme to hydroxylamine showed that the phosphorylated enzyme is of an acyl phosphate type. The present results are consistent with the probability that the phosphorylation results from reversal of late steps in the Ca-2plus transport process. The results clearly show that the phosphorylated enzyme is stabilized by a great increase in entropy upon its formation from the enzyme-phosphate complex.


Acute pyelonephritis as a cause of late transplant dysfunction.
In a renal transplant recipient, acute pyelonephritis of the allograft developed in association with acute deterioration of renal function. No other cause of renal dysfunction was delineated, and the serum creatinine level promptly returned to baseline with antimicrobial therapy. Acute pyelonephritis is an important cause of late transplant dysfunction, and prompt diagnosis and treatment result in complete recovery of renal function.


Rational construction of a robust nanoprobe for highly selective and sensitive nitrite and formaldehyde detection and imaging in real foods.
Nitrite (NO2-) and formaldehyde (FA) are practice common food hazards, seriously threatening human health. Herein, for the first time a de novo nanoprobe, named MTB, with a single response group exhibiting different optical signals for NO2-/FA was reported, which had the following characteristics: i) An adamantane-labeled small molecule NI-adH grafted with polycyclodextrin (Poly-β-CD) to form MTB with excellent water-solubility and biocompatibility. ii) O-phenylenediamine (OPD) with photoinduced electron transfer (PET) played both a fluorescence quencher and as NO2-/FA trappers. Interestingly, fixed on pH6.0, OPD rapidly reacted with NO2- forming triazoles, inhibiting the PET effect and releasing bright fluorescence at 530 nm. While adding FA, OPD ultrafast formed Schiff-base, and MTB absorption red-shifted from 452 nm to 545 nm. Moreover, MTB exhibited excellent selectivity, high sensitivity (21.8 nM/17.1 nM), and rapid response towards (60 s/65 s) NO2-/FA. Impressively, MTB has been successfully adopted to detect NO2-/FA in real foods with satisfactory results.


Contributions of Extracellular Vesicles to Fungal Biofilm Pathogenesis.
Extracellular vesicles (EVs) are produced by all kingdoms of life and have been increasingly recognized as a key aspect of microbial pathogenicity. These membrane-bound compartments serve as secretory vehicles for the delivery of macromolecules to the extracellular environment. Studies over the past several decades have revealed that microbial EVs are highly suited to the biology and environmental context of the organism secreting them. Fungal EVs have been described in at least 12 species and have diverse functions. These functions include, but are not limited to, molecular transport across the cell wall, immunomodulation, cell-cell communication, export of virulence factors and nucleic acids, extracellular matrix (ECM) production, and induction of drug resistance. This chapter will explore the contributions of EVs to fungal pathogenesis and virulence, with a detailed focus on the role of C. albicans biofilm EVs in matrix biogenesis and antifungal resistance. Brief commentary on EV function in bacterial biofilms will also be provided for comparison, and suggestions for areas of future investigation in this field will be discussed.


[Modern lipid-lowering drugs-A means to counter the problem of undertreatment?]
An elevated low-density lipoproteincholesterol (LDL-C) level is one of the most important modifiable cardiovascular risk factors. Despite potent combination treatment, the LDL‑C target values are not achieved in many high-risk patients. Presentation of the rationale for lowering LDL‑C, the current status of lipid-lowering treatment and established and novel approaches to lower LDL‑C. Based on the large outcome trials with ezetimibe and antibodies against proprotein convertase subtilisin-kexin type 9 (PCSK9), the professional societies recommend LDL‑C target values depending on the individual cardiovascular risk. For patients with manifest atherosclerosis, the LDL‑C target value is < 55 mg/dL (1.4 mmol/L). The LDL‑C target values are only achieved in the minority of patients. The reasons for this include a lack of awareness among treating physicians, low medication adherence, restrictions in prescriptions and intolerance. On the basis of a healthy lifestyle, statins are the cornerstone of LDL-C-lowering treatment. If LDL‑C targets are not achieved, the cholesterol absorption inhibitor ezetimibe is additionally recommended. As a third step, PCSK9 antibodies are added. A novel drug to lower LDL‑C is the orally available bempedoic acid, which acts on the same metabolic pathway as statins but is specifically activated in the liver and not in the skeletal muscle. Another novel drug is inclisiran, which acts as an intracellular PCSK9 inhibitor through RNA interference. Inclisiran is administered subcutaneously only every 6 months and has potential advantages regarding adherence. According to the new recommendations, active substances should be combined and fixed-dose combinations should be used early for lowering of LDL‑C. Using established and novel LDL-C-lowering drugs, the recommended LDL‑C target values can be achieved in the majority of patients with a high cardiovascular risk.


Identification of herniated nucleus pulposis in spinal cord injury.
Five cases of documented traumatic herniated nucleus pulposis are presented all occurring within the cervical region. The incidence of herniated disc in cervical spinal cord injury is 0.7%. The incidence of herniated disc in bilateral facet dislocations is 2.3%. The common features are radicular pain, incomplete syndrome, and bilateral facet dislocations. A routine myelogram is the most helpful test to establish the diagnosis.


Collection, storage, inspection and quality control of platelet concentrates obtained by apheresis: The situation in Spain.
Diverse variables are involved in apheresis platelet collection, processing and storage. This survey shows how these are realized in Spain. An analysis of collected data was performed in a questionnaire completed by ten Transfusion Centers (TC) which perform between 50 and 520 apheresis procedures per month. This information comprises the procedures used to collect, inspect and store apheresis platelet concentrates (PC), and quality control data. Macroscopic inspection of PC is performed in all TC, especially during the first few hours post-collection and before distribution. The type of processor, duration of post-collection resting periods and temperature from the time of collection until distribution are similar in all TC. In 80% of TC, PC with small and scarce aggregates are distributed to transfusion services. The presence of clumps is influenced by type of processor, female donor, cold ambient temperature and collection of hyperconcentrated platelets, and is often recurrent in the same donor, although some TC have not found any influential variables. Overall, no objective inspection methods are followed, although there are exceptions. The degree of compliance with quality control parameters, such as the number of units studied, mean platelet yield, residual leukocyte counts and pH at expiry date, is acceptable in all TC. Compliance in terms of number of microbiological culture samples is variable. The usual practice in Spanish TC with respect to the collection, post-collection handling and storage of apheresis PC can be considered uniform, although some specific aspects of analyses should follow more objective methods.


Making better scar: Emerging approaches for modifying mechanical and electrical properties following infarction and ablation.
Following myocardial infarction (MI), damaged myocytes are replaced by collagenous scar tissue, which serves an important mechanical function - maintaining integrity of the heart wall against enormous mechanical forces - but also disrupts electrical function as structural and electrical remodeling in the infarct and borderzone predispose to re-entry and ventricular tachycardia. Novel emerging regenerative approaches aim to replace this scar tissue with viable myocytes. Yet an alternative strategy of therapeutically modifying selected scar properties may also prove important, and in some cases may offer similar benefits with lower risk or regulatory complexity. Here, we review potential goals for such modifications as well as recent proof-of-concept studies employing specific modifications, including gene therapy to locally increase conduction velocity or prolong the refractory period in and around the infarct scar, and modification of scar anisotropy to improve regional mechanics and pump function. Another advantage of scar modification techniques is that they have applications well beyond MI. In particular, ablation treats electrical abnormalities of the heart by intentionally generating scar to block aberrant conduction pathways. Yet in diseases such as atrial fibrillation (AF) where ablation can be extensive, treating the electrical disorder can significantly impair mechanical function. Creating smaller, denser scars that more effectively block conduction, and choosing the location of those lesions by balancing their electrical and mechanical impacts, could significantly improve outcomes for AF patients. We review some recent advances in this area, including the use of computational models to predict the mechanical effects of specific lesion sets and gene therapy for functional ablation. Overall, emerging techniques for modifying scar properties represents a potentially important set of tools for improving patient outcomes across a range of heart diseases, whether used in place of or as an adjunct to regenerative approaches.


Continuous intragastric pH measurement in the critically ill and treatment with parenteral ranitidine.
Continuous measurement of gastric pH using a flexible pH electrode attached to a NG tube was performed in nineteen critically ill patients. The gastric pH readings correlated well with hourly intermittent pH values using indicator strips. Hypotension, physiotherapy and septicaemia was consistently associated with falls in gastric pH. A continuous infusion of Ranitidine, a H2-receptor antagonist, was titrated against the continuously measured gastric pH in an attempt to keep it above a pH of 4. This was successfully achieved in sixteen of the nineteen patients using widely variable doses of Ranitidine. The three patients whose gastric pH remained low all had severe septicaemia.


Lipins, lipinopathies, and the modulation of cellular lipid storage and signaling.
Members of the lipin protein family are phosphatidate phosphatase (PAP) enzymes, which catalyze the dephosphorylation of phosphatidic acid to diacylglycerol, the penultimate step in TAG synthesis. Lipins are unique among the glycerolipid biosynthetic enzymes in that they also promote fatty acid oxidation through their activity as co-regulators of gene expression by DNA-bound transcription factors. Lipin function has been evolutionarily conserved from a single ortholog in yeast to the mammalian family of three lipin proteins-lipin-1, lipin-2, and lipin-3. In mice and humans, the levels of lipin activity are a determinant of TAG storage in diverse cell types, and humans with deficiency in lipin-1 or lipin-2 have severe metabolic diseases. Recent work has highlighted the complex physiological interactions between members of the lipin protein family, which exhibit both overlapping and unique functions in specific tissues. The analysis of "lipinopathies" in mouse models and in humans has revealed an important role for lipin activity in the regulation of lipid intermediates (phosphatidate and diacylglycerol), which influence fundamental cellular processes including adipocyte and nerve cell differentiation, adipocyte lipolysis, and hepatic insulin signaling. The elucidation of lipin molecular and physiological functions could lead to novel approaches to modulate cellular lipid storage and metabolic disease.


Real-time integration of 2D intracardiac echocardiography and 3D electroanatomical mapping to guide ventricular tachycardia ablation.
Ablation of left ventricular tachycardia (LV VT) involves point-by-point reconstruction of the three-dimensional (3D) virtual anatomy. It is time consuming and requires substantial fluoroscopy exposure. Two-dimensional (2D) intracardiac echocardiography (ICE) affords real-time imaging of the cardiac structures. This study sought to evaluate a mapping system integrating ICE with 3D mapping to guide VT ablation. Seventeen patients (16 men, 62 +/- 11 years, LV ejection fraction 40% +/- 15%) had ablation of nonidiopathic VT guided using a system integrating 3D mapping and ICE. ICE probe with a location sensor tracked by the mapping system was positioned in the right heart. Endocardial contours traced on gated images of the LV were used to generate a registered 3D map. Regional wall motion abnormalities (WMA) were tagged. 3D maps were created in 26 +/- 8 min, before entering the LV and without fluoroscopy. Maps were built from 23 +/- 7 contours. Regional WMA corresponded to low bipolar voltage (<0.5 mV). Procedure time was 240 +/- 77 min, with fluoroscopy time of 25 +/- 12 min. LV volume by ICE was 172 +/- 119 cm(3) versus 164 +/- 112 cm(3) for the point-by-point maps (P = .5). Scar area by ICE was 33 +/- 32 cm(2) versus 36 +/- 33 cm(2) for voltage mapping (P = .4). At 5 +/- 4 months, 12 patients (71%) were free of VT. A system combining 2D ICE and 3D mapping can reconstruct a 3D shell of the LV, including a substrate map based on regional WMA without the need to enter the LV. VT ablation guided using this approach is safe and effective.


Structure of the Abelson murine leukemia virus genome.
Virions produced from cells transformed by A-MuLV contain a 30S, 5.6 kb RNA that can be translated in a cell-free system to form the characteristic A-MuLV protein. This RNA was mapped by heteroduplex methods using DNA probes from M-MuLV, the presumed parent of A-MuLV. The overall organization of the RNA was determined by using full-length M-MuLV reverse transcribed DNA and visualizing the heteroduplexes in the electron microscope. This showed that A-MuLV and M-MuLV have homologous sequences at both ends of their RNAs but that the central portion of the A-MuLV genome is not homologous to sequences in M-MuLV RNA. A precise measure of the lengths of the shared regions was obtained by using S1 nuclease to digest hybrids between 32P-labeled M-MuLV DNA and A-MuLV RNA; the resulting fragments were analyzed for their length by electrophoresis. The regions of homology were shown to be 1320 nucleotides long at the 5' end and 730 nucleotides long at the 3' end. Thus approximately 6200 nucleotides of the approximately 8300 in M-MuLV RNA were deleted when the A-MuLV genome was formed, but an insert of 3600 nucleotides, presumably derived from the normal murine genome, was inserted in place of the deleted region.


Mineral oil and synthetic hydrocarbons in cosmetic lip products.
Lipsticks and lip care products may contain saturated hydrocarbons which either stem from mineral oil saturated hydrocarbons (MOSH) or are synthetic, that is polyolefin oligomeric saturated hydrocarbons (POSH). Some of these hydrocarbons are strongly accumulated and form granulomas in human tissues, which prompted Cosmetics Europe (former Colipa) to issue a recommendation for their use in lip care and oral products. From 2012 to 2014, MOSH+POSH were determined in 175 cosmetic lip products taken from the Swiss market in order to estimate their contribution to human exposure. Mineral oil saturated hydrocarbons and POSH were extracted and analysed by GC with FID. Areas were integrated as a total as well as by mass ranges with cuts at n-C25 and n-C34 to characterize the molecular mass distribution. About 68% of the products contained at least 5% MOSH+POSH (total concentration). For regular users, these products would be major contributors to their MOSH+POSH exposure. About 31% of the products contained more than 32% MOSH+POSH. Their regular usage would amount in an estimated MOSH+POSH exposure exceeding the highest estimated dietary exposure. The majority of the products contained hydrocarbons with a molecular mass range which was not in line with the recommendations of Cosmetics Europe. Taking into account that material applied to the lips largely ends up being ingested, MOSH and POSH levels should be reduced in the majority of cosmetic lip products. As the extensive evaluation of the data available on MOSH (EFSA J., 10, 2012, 2704) did not enable the specification of limits considered as safe, the present level of dietary exposure and its evaluation as 'of potential concern' provide the relevant bench mark, which means that lip products should contain clearly less than 5% MOSH+POSH.


Conformational changes in the DNA of hybridoma cells from pristane treated mice.
The effects of pristane on the DNA of hybridoma cells propagated as ascitic tumors in pristane-primed BALB/c mice were determined using flow cytometric analyses. Hybridoma cells maintained in vitro or cell isolates from solid tumors which developed in unprimed mice injected with hybridoma cells exhibited similar propidium iodide (PI) staining characteristics. In contrast, PI stained cells isolated from ascites which developed in pristane-primed mice injected with the hybridoma cells displayed significant decreases in fluorescence intensity. Diphenylamine studies and analyses of pH 10 treated cells indicated that the actual DNA content of the hybridoma cells was not altered by exposure to pristane. Furthermore, the altered staining characteristics of the ascitic tumor cells were reversible in that the fluorescence intensity after serial in vitro passage of the ascites cells was similar to that of the parent cell line which had not been exposed to pristane. In addition, there was a direct correlation between the altered PI staining characteristics and the presence of cell-associated pristane as determined by gas-liquid chromatography analyses of cell extracts. Collectively these results suggest that pristane may have a direct effect on the DNA conformation of hybridoma cells which may in turn enhance their growth as ascitic tumors. The possible role of such an altered DNA conformation in hybridoma cells on the in vivo development of ascites is discussed.


Using hiPSC-CMs to Examine Mechanisms of Catecholaminergic Polymorphic Ventricular Tachycardia.
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal inherited cardiac arrhythmia condition, triggered by physical or acute emotional stress, that predominantly expresses early in life. Gain-of-function mutations in the cardiac ryanodine receptor gene (RYR2) account for the majority of CPVT cases, causing substantial disruption of intracellular calcium (Ca2+ ) homeostasis particularly during the periods of β-adrenergic receptor stimulation. However, the highly variable penetrance, patient outcomes, and drug responses observed in clinical practice remain unexplained, even for patients with well-established founder RyR2 mutations. Therefore, investigation of the electrophysiological consequences of CPVT-causing RyR2 mutations is crucial to better understand the pathophysiology of the disease. The development of strategies for reprogramming human somatic cells to human induced pluripotent stem cells (hiPSCs) has provided a unique opportunity to study inherited arrhythmias, due to the ability of hiPSCs to differentiate down a cardiac lineage. Employment of genome editing enables generation of disease-specific cell lines from healthy and diseased patient-derived hiPSCs, which subsequently can be differentiated into cardiomyocytes. This paper describes the means for establishing an hiPSC-based model of CPVT in order to recapitulate the disease phenotype in vitro and investigate underlying pathophysiological mechanisms. The framework of this approach has the potential to contribute to disease modeling and personalized medicine using hiPSC-derived cardiomyocytes. © 2021 Wiley Periodicals LLC.


Analysis of perchlorate, thiocyanate, nitrate and iodide in human amniotic fluid using ion chromatography and electrospray tandem mass spectrometry.
Because of health concerns surrounding in utero exposure to perchlorate, we developed a sensitive and selective method for quantifying iodide, as well as perchlorate and other sodium-iodide symporter (NIS) inhibitors in human amniotic fluid using ion chromatography coupled with electrospray ionization tandem mass spectrometry. Iodide and NIS inhibitors were quantified using a stable isotope-labeled internal standards (Cl18O4-, S13CN- and 15NO3- with excellent assay accuracy of 100%, 98%, 99%, 95% for perchlorate, thiocyanate, nitrate and iodide, respectively, in triplicate analysis of spiked amniotic fluid sample). Excellent analytical precision (<5.2% RSD for all analytes) was found when amniotic fluid quality control pools were repetitively analyzed for iodide and NIS-inhibitors. Selective chromatography and tandem mass spectrometry reduced the need for sample cleanup, resulting in a rugged and rapid method capable of routinely analyzing 75 samples/day. Analytical response was linear across the physiologically relevant concentration range for the analytes. Analysis of a set of 48 amniotic fluid samples identified the range and median levels for perchlorate (0.057-0.71, 0.18 microg/L), thiocyanate (<10-5860, 89 microg/L), nitrate (650-8900, 1620 microg/L) and iodide (1.7-170, 8.1 microg/L). This selective, sensitive, and rapid method will help assess exposure of the developing fetus to low levels of NIS-inhibitors and their potential to inhibit thyroid function.


The overlap of bronchiectasis and immunodeficiency with asthma.
Bronchiectasis should be considered as a differential diagnosis for, as well as a comorbidity in, patients with asthma, especially severe or long-standing asthma. Chronic airway inflammation is thought to be the primary cause, as with chronic or recurrent pulmonary infection and autoimmune conditions that involve the airways. Consequently, immunodeficiencies with associated increased susceptibility to respiratory tract infections or chronic inflammatory airways also increase the risk of developing bronchiectasis. Chronic bronchiectasis is associated with impaired mucociliary clearance and increased bronchial secretions, leading to airway obstruction and airflow limitation, which can lead to exacerbation of underlying asthma or increased asthma symptoms.


Inhibition of cranial neural crest cell development by vitamin A in the cultured chick embryo.
Chick embryos at stage 8, prior to neural crest cell migration, were explanted on whole egg medium with or without vitamin A and cultured for 3 days. Sections through the head regions showed that the cranial neural crest cells had migrated into the first visceral arch in the controls but were absent from this structure in the treated embryos. These observations suggest that vitamin A inhibits neural crest cell development or migration, an effect which may in part account for the facial malformations produced by excess vitamin A.


A survey of the prescribing and administration of drugs in a long-term care institution for the elderly.
The prescription and administration of drugs (especially of the neuroactive class) was observed in 131 patients in an extended care facility. The average number of neuroactive drugs prescribed (2.1) was distinctly different from the average number administered (1.3) because of the large number of pro re nata (prn) prescriptions. More neuroactive substances were prescribed for patients with superior mentation and minimal physical disability; the difference between low and high groups was 1.7 (mentation) and 2.8 (physical status). The most common neuroactive drugs prescribed were: 1) analgesics, 2) major tranquilizers, and 3) hypnotics. Questionable prescribing practices were demonstrated by the fact that 30 patients had prescriptions for 38 "not-recommended"drugs; 23 of these prescriptions were for propoxyphene compound. After requiring physicians to rewrite drug orders every thirty days, a survey made ten months later showed that there was a decline (0.8) in the number of drugs prescribed per patient and a slight increase (0.45) in the number of drugs administered. Professional drug surveillance is crucial for improving the therapeutic process. At least two modifications of current prescribing practices are recommended: 1) a record should always be made of the precise condition(s) under which a drug prescribed "prn" is to be administered; and 2) a strong effort should be made to reduce the total number of drug prescriptions. The results of this survey suggest that certain procedural matters necessitating change are not in themselves the most substantive factors in improvement. Present "third party" review mechanisms likely will not ameliorate the current situation. It will be necessary to implement complex organizational changes in most extended care facilities.


A bullous rash.
A 3-year-old boy presented with a 5-day history of bullous skin lesions localised mainly in the upper and lower limbs and in the genital region (figure 1). Lesions were not pruritic nor painful and showed a central crust. There was no family history of skin disorders or autoimmune diseases. The child never had fever and his physical examination was otherwise unremarkable.


Postoperative pain with or without nasal splints after septoplasty and inferior turbinate reduction.
To determine the effect of intranasal Doyle splints on postoperative pain following septoplasty and inferior turbinate reduction (ITR). Changes in Nasal Obstruction Symptom Evaluation (NOSE) scores were also evaluated. A prospective cohort study conducted from January 2017 to January 2019. Patients were recruited if they experienced nasal obstruction due to septal deviation and inferior turbinate hypertrophy, and failed a one-month trial of intranasal corticosteroids. All patients underwent septoplasty with ITR, and either had Doyle splints or no splints placed. Patients were prescribed hydrocodone-acetaminophen 5-325 mg and asked to keep a daily log of pain medication use and visual analog scale (VAS) scores. Pain logs and NOSE scores were compared between patients who had splints versus patients who had no splints placed after septoplasty and ITR over the first postoperative week. NOSE scores were also collected at every postoperative visit (1 week, 1 month, and 6 months). Fifty-seven patients were enrolled (37 splints, 20 no-splints). The median postoperative pain VAS score was 3.0 (interquartile range [IQR] 2.0-5.0) for the splint group and 4.0 (IQR 2.0-5.0) for the no-splint group (P = 0.906). The median postoperative pain medication requirement in morphine equivalents at the first postoperative visit was 5.4 mg/day (IQR 2.0-13.3) for the splint group and 8.4 mg/day (IQR 1.8-15.3) for the no-splint group (P = 0.833). There were no statistically significant differences in postoperative pain VAS scores or pain medication use between the two groups. All patients experienced significant reductions in NOSE scores postoperatively.


Release of cartilage macromolecules into the synovial fluid in patients with acute and prolonged phases of reactive arthritis.
Extensive changes in articular cartilage metabolism occur during the acute phase of reactive arthritis, as indicated by altered release of cartilage macromolecules into synovial fluid (SF) demonstrated immunochemically. Nevertheless, permanent cartilage lesions are rare in this disease. To monitor specific events during the evolution of reactive arthritis, we investigated the content of cartilage macromolecules in sequentially obtained SF samples from 22 patients. Two groups of proteoglycan epitopes, the glycosaminoglycan-rich region of aggrecan (referred to as proteoglycan) and its hyaluronan-binding region (HABr), as well as one matrix protein, cartilage oligomeric matrix protein (COMP), were quantified by immunoassay. SF proteoglycan concentrations, which were initially elevated, decreased significantly with prolonged arthritis, whereas COMP levels changed less markedly and levels of HABr remained stable. There was a positive correlation between SF and serum concentrations of COMP in samples obtained during the early phase of the disease. Cartilage involvement in reactive arthritis is transient, in contrast to findings in rheumatoid arthritis. Reactive arthritis should therefore be a suitable model for studies of repair processes in cartilage, which will facilitate understanding of the pathophysiology of cartilage involvement in arthritis.


Influence of endogenous catalase activity on the sensitivity of the oral bacterium Actinobacillus actinomycetemcomitans and the oral haemophili to the bactericidal properties of hydrogen peroxide.
Actinobacillus actinomycetemcomitans and the genetically-related oral haemophili (Haemophilus segnis, Haemophilus aprhophilus and Haemophilus paraphrophilus) exhibit a range of sensitivities to the lethal effect of hydrogen peroxide (H2O2), A. actinomycetemcomitans being the most resistant. To extend this information, susceptibility to a range of H2O2 concentrations (10(-6)-10(-3) M) was assessed by incubating bacterial suspensions for 1 h at 37 degrees C in the presence of H2O2 and spreading the suspensions on chocolate agar plates to determine the concentration of H2O2 producing a 50 per cent reduction in colony-forming units (LD50). Catalase activity was quantified with a Clark-type oxygen electrode, which polarographically monitored the formation of dissolved oxygen in bacterial suspensions or sonicates following addition of reagent H2O2. Sensitivity to H2O2 did not correlate with catalase activity, either in intact cells or in bacterial sonicates. Specifically, some bacterial strains with undetectable catalase activity were highly resistant to H2O2. Micromolar concentrations of sodium azide which completely inhibited cell-associated catalase activity did not affect the resistance of A. actinomycetemcomitans to H2O2. Thus, the endogenous catalase activity of A. actinomycetemcomitans and certain oral haemophili is not an important determinant of resistance to the bactericidal effects of H2O2.


Prevalence and predictive signs for gastrointestinal lesions in premenopausal women with iron deficiency anemia.
The reported rates of gastrointestinal (GI) lesions among pre-menopausal women with iron deficiency anemia (IDA) vary considerably. To assess the prevalence of significant gastrointestinal lesions among symptomatic and asymptomatic pre-menopausal women with IDA, and to shed light on potential predictors of their presence. Clinical, endoscopic, and histological data was collected from 116 pre-menopausal women with IDA. All women underwent upper and lower gastrointestinal tract endoscopies, duodenal biopsies, and small bowel evaluation with small bowel series or computed tomography. The mean age was 33 years (range: 18-45). Clinically, significant lesions were demonstrated in 30%, the majority in the upper gastrointestinal tract. Helicobacter pylori gastritis was the most common finding (16%). Celiac disease was detected in 6%. No malignant lesions were detected. The prevalence of lesions was highest among women with symptoms of heartburn and regurgitation. The presence of upper gastrointestinal symptoms (OR: 3.67, 95%CI: 2.14-5.03; P = 0.002), MCV lower than 70 pg (OR: 1.88, 95%CI: 1.27-3.91; P = 0.04), and hemoglobin levels less than 10 g/dl (OR: 1.71, 95%CI: 1.19-4.07; P = 0.05) were associated with an increased likelihood of significant gastrointestinal lesions; history of heavy menstrual blood loss was associated with negative findings (OR: 0.46, 95%CI: 0.27-0.69; P = 0.002). Upper GI findings, mainly HP gastritis and celiac disease, were the most common pathologic findings. Initial evaluation of IDA in premenopausal women may include urea breath test and celiac serology. Further endoscopic evaluation can be reserved for those women who are found to be negative in the initial evaluation, as well as in cases of failure of IDA remission after successful HP eradication.


Early postnatal changes of lipoprotein subclass profile in late preterm infants.
Late preterm infants (LPIs; 34-37 gestational weeks at birth) have higher risk for several morbidities than do term infants (TIs). It has been suggested that a cholesterol and fatty acid supply may improve their outcomes. We investigated the lipoprotein subclass profile in LPIs to evaluate their early postnatal lipid metabolism. Eighty-one infants (25 LPIs, 56 TIs) were included. Cholesterol and triglyceride (TG) concentrations in 12 lipoprotein subclasses were measured at birth and at 1 month using HPLC. In LPIs, the cord blood exhibited higher cholesterol concentrations in medium and large subclasses of very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) compared to the values in TIs. During the first month of life, LPIs had greater increases in cholesterol concentrations of medium and large subclasses of VLDL than TIs, whereas postnatal increases in cholesterol concentrations of medium and large subclasses of LDL and HDL were smaller. TG concentrations were not different in each VLDL subclass at birth and at 1 month. In LPIs, cord blood lipoprotein subclass profiles and the early postnatal change exhibited different, especially in cholesterol concentrations.


Safety of intravenous methamphetamine administration during treatment with bupropion.
Methamphetamine dependence is a growing problem for which no medication treatments have proven effective. We evaluated bupropion, an antidepressant with beneficial effects for the treatment of nicotine dependence, in patients with methamphetamine dependence, to assess the safety and tolerability of methamphetamine administration during bupropion treatment. Twenty-six participants entered the study and 20 completed the protocol. Participants received intravenous methamphetamine (0, 15, and 30 mg) before and after randomization to twice-daily bupropion (150 mg SR) or matched placebo. Dependent measures included cardiovascular effects of methamphetamine, methamphetamine and amphetamine pharmacokinetics, and peak and trough plasma concentrations of bupropion and its metabolites. Bupropion treatment was well tolerated, with bupropion- and placebo-treated groups reporting similar rates of adverse events. Methamphetamine administration was associated with expected stimulant cardiovascular effects, and these were not accentuated by bupropion treatment. Instead, there was a trend for bupropion to reduce methamphetamine-associated increases in blood pressure and a statistically significant reduction in methamphetamine-associated increases in heart rate. Pharmacokinetic analysis revealed that bupropion treatment reduced the plasma clearance of methamphetamine and also reduced the appearance of amphetamine in the plasma. Methamphetamine administration did not alter the peak and trough plasma concentrations of bupropion or its metabolites. Methamphetamine administration was well tolerated during bupropion treatment. There was no evidence of additive cardiovascular effects when the drugs were coadministered. This study provides initial evidence for the safety of prescribing bupropion for the treatment of methamphetamine abuse and dependence. The impact of bupropion treatment in patients who abuse larger doses of methamphetamine remains undetermined.


The role of mechanobiology in tendon healing.
Mechanical cues affect tendon healing, homeostasis, and development in a variety of settings. Alterations in the mechanical environment are known to result in changes in the expression of extracellular matrix proteins, growth factors, transcription factors, and cytokines that can alter tendon structure and cell viability. Loss of muscle force in utero or in the immediate postnatal period delays tendon and enthesis development. The response of healing tendons to mechanical load varies depending on anatomic location. Flexor tendons require motion to prevent adhesion formation, yet excessive force results in gap formation and subsequent weakening of the repair. Excessive motion in the setting of anterior cruciate ligament reconstruction causes accumulation of macrophages, which are detrimental to tendon graft healing. Complete removal of load is detrimental to rotator cuff healing; yet, large forces are also harmful. Controlled loading can enhance healing in most settings; however, a fine balance must be reached between loads that are too low (leading to a catabolic state) and too high (leading to microdamage). This review will summarize existing knowledge of the mechanobiology of tendon development, homeostasis, and healing.


Influence of modified starches as wall materials on the properties of spray-dried lemongrass oil.
The use of lemongrass oil as food preservative present great potential, however it has high volatility and intense aroma, making them limited to be used as food additives. Microencapsulation processes become interesting alternatives to overcome these issues. This work investigated the influence of the partial replacement of gum arabic by modified starches on the microencapsulation of lemongrass oil as core material. Gum arabic and its combinations with modified starches: cassava and corn maltodextrins with different dextrose equivalent (DE) and octenyl succinic anhydride modified starch (OSA-starch) were studied. The emulsions were spray dried at controlled temperature of 170 °C. The evaluated parameters particles solubility, moisture content, and oil composition did not showed significant differences among the treatments. Replacement of gum arabic by maltodextrin DE20 and OSA-starch resulted in higher wetting times. Oil retention was increased (81.2%) when gum arabic was replaced by OSA-starch; the treatment without substitution, with only gum arabic had 67.5% of oil retention. Application of OSA-starch in association with gum arabic in microencapsulation by spray drying of lemongrass oil presented greater potential to be used due to its higher oil retention. Polymer blends should be assessed since they present advantages over individually applied polymers. Although maltodextrins show some differences compared to the treatment with only gum arabic, it may also be a viable alternative because of its lower cost.


Renal carbuncle: comparison between surgical open drainage and closed percutaneous drainage.
This article represents a retrospective study of 12 patients with renal carbuncle treated at the combined urological services of The Mason Clinic in Seattle, Washington, and Madigan Army Medical Center in Tacoma, Washington. All patients were initially treated with antibiotics. Two recovered without further treatment. Of the 10 patients who failed to respond, 2 underwent nephrectomy for nonfunctioning kidneys, 4 underwent closed percutaneous drainage, and 4 underwent surgical open drainage. All patients treated with open surgical drainage recovered and retained functioning kidneys. Of the 4 patients who underwent closed percutaneous drainage, 2 failed to respond and required subsequent emergency nephrectomy because of sepsis. The authors believe that renal exploration and open drainage should be the initial definitive mode of surgical treatment of renal carbuncle in those patients who fail antibiotic therapy alone.


Nuclear Overhauser effect as a probe of molecular structure, dynamics and order of axially reorienting molecules in membranes.
The location, orientation, order and dynamics of cholesterol in model membranes have been well characterized, therefore cholesterol is an ideal molecule for developing new methods for studying structured molecules undergoing rapid axially symmetric reorientation. The use of (13)C filtering via short contact cross polarization transfer to (1)H allows the recovery of the weak cholesterol (1)H magic angle spinning NMR signals from beneath the strong phospholipid background in bicelles composed of chain perdeuterated dimyristoyl phosphatidylcholine/dicaproyl phosphatidylcholine/[3,4-(13)C]-cholesterol. Measurements of the nuclear Overhauser enhancement for (1)H nuclei located in the first ring of cholesterol are interpreted in terms of a simple two motion model consisting of axial reorientation, with a correlation time τ∥, and a slower reorientation of the diffusion axis relative to the bilayer normal, with correlation time τ⊥. This approach can be extended to other molecules which undergo rapid axial reorientation such as small membrane associated peptides.


Application of multi-echo Dixon and MRS in quantifying hepatic fat content and staging liver fibrosis.
This study associated the liver proton density fat fraction (PDFF), measured by multi-echo Dixon (ME-Dixon) and breath-hold single-voxel high-speed T2-corrected multi-echo 1H magnetic resonance spectroscopy (HISTO) at 1.5 T, with serum biomarkers and liver fibrosis stages. This prospective study enrolled 75 patients suspected of liver fibrosis and scheduled for liver biopsy and 23 healthy participants with normal liver function. The participant underwent ME-Dixon and HISTO scanning. The agreement of PDFF measured by ME-Dixon (PDFF-D) and HISTO (PDFF-H) were compared. Correlations between PDFF and serum fat biomarkers (total cholesterol, triglyceride, and high- and low-density lipoproteins) and the liver fibrosis stages were assessed. PDFF were compared among the liver fibrosis stages (F0-F4) based on clinical liver biopsies. The Bland-Altman plot showed agreement between PDFF-D and PDFF-H(LoA, - 4.44 to 6.75), which have high consistency (ICC 0.752, P < 0.001). The correlations with the blood serum markers were mild to moderate (PDFF-H: r = 0.261-0.410, P < 0.01; PDFF-D: r = 0.265-0.367, P < 0.01). PDFF-D, PDFF-H, and steatosis were distributed similarly among the liver fibrosis stages. PDFF-H showed a slight negative correlation with the liver fibrosis stages (r = - 0.220, P = 0.04). Both ME-Dixon and HISTO sequences measured liver fat content noninvasively. Liver fat content was not directly associated with liver fibrosis stages.


IL-4-secreting CD4+ T cells are crucial to the development of CD8+ T-cell responses against malaria liver stages.
CD4+ T cells are crucial to the development of CD8+ T cell responses against hepatocytes infected with malaria parasites. In the absence of CD4+ T cells, CD8+ T cells initiate a seemingly normal differentiation and proliferation during the first few days after immunization. However, this response fails to develop further and is reduced by more than 90%, compared to that observed in the presence of CD4+ T cells. We report here that interleukin-4 (IL-4) secreted by CD4+ T cells is essential to the full development of this CD8+ T cell response. This is the first demonstration that IL-4 is a mediator of CD4/CD8 cross-talk leading to the development of immunity against an infectious pathogen.


Atrazine effects on meiobenthic assemblages of a modular estuarine mesocosm.
Atrazine is a widely used herbicide in the US found at levels ranging from <10 ng/L to 62.5 microg/L in estuaries throughout the southeast. Effects of atrazine on estuarine meiobenthic assemblages chronically exposed to environmentally relevant concentrations are unknown. The purpose of our research was to assess effects of atrazine on meiobenthos at concentrations near the proposed USEPA SWQC (26 microg/L) using modular estuarine salt marsh mesocosms as a field surrogate. Indigenous copepod and nematode densities were assessed after 28 days of exposure in transplanted colonization chambers. Cluster analysis showed a group characterized by low copepod densities, mostly atrazine exposed chambers, and a group containing all but one control chamber. The later group included chambers with high densities of the copepods Paronychocamptus wilsoni and Enhydrosoma baruchi. Compared to controls, copepod densities was approximately 70% lower in atrazine chambers, with three of the most common copepod species (E. baruchi, Onychocamptus sp. and P. wilsoni) showing an average of 50-70% reduction in population densities (p<0.05). Although nematode density did not differ between atrazine and control chambers, the nematode-to-copepod ratio was significantly higher in atrazine (9.95+/-7.61; p=0.011) than in control chambers (0.61+/-0.35). Our findings suggest that chronic exposures over multiple generations to atrazine at concentrations near the proposed USEPA SWQC could have significant effects on the abundance and composition of estuarine meiobenthic copepod assemblages.


Quality and rate of extracellular polysaccharides produced by Rhizobium meliloti and their inducing effect on polygalacturonase production in legume roots as derived from the presence of extrachromosomal DNA.
The ability of extracellular polysaccharides of different strains of Rhizobium meliloti to induce the production of polygalacturonase by roots of Medicago sativa seedlings has been studied. Some strains showed a high inducing activity while those derived from them, after treatment with acridine orange and in which extrachromosomal DNA was absent, did not show this character. A comparative study of polysaccharide production and preliminary studies on the chemical composition of the active fractions obtained after Sephadex G-25 filtration indicated that the monomers which form the active fractions are qualitatively and quantitatively different according to their origin.


MicroRNA-302b Enhances the Sensitivity of Hepatocellular Carcinoma Cell Lines to 5-FU via Targeting Mcl-1 and DPYD.
MiR-302b is a member of miR-302-367 cluster. The miR-302-367 cluster played important roles in maintaining pluripotency in human embryonic stem cells (hESCs) and has been proved to be capable of suppressing cell growth in several types of cancer cell lines including Hepatocellular Carcinoma (HCC) Cell lines. However, the role that miR-302b plays in the 5-Fluorouracil (5-FU) sensitivity of HCC has not been known. This study showed that miR-302b could enhance the sensitivity to 5-FU in HCC cell lines and verified its two putative targeted genes responsible for its 5-FU sensitivity.


Exploring the role of practical nursing wisdom in the care of patients with urinary problems at the end of life: a qualitative interview study.
This study examined how nurses understand urinary problems at the end of life, and identified sources of evidence upon which they base their practice through semi-structured qualitative interviews. The aim was to decide whether research or interventions (such as formulation of best practice guidelines) could improve continence care at the end of life. There is little evidence in nursing literature to indicate how nurses should manage urinary problems at the end of life. Evidence is particularly lacking regarding the insertion of indwelling urinary catheters. This was an applied qualitative interview study which used the 'guided interview' approach. Twelve participants who worked in two hospital wards and one hospice were interviewed about management of patients with urinary problems approaching the end of life. The transcribed interviews were organised using the qualitative analysis software qsr NVivo version 10 (QSR International, Melbourne, Australia). Constant comparison was used to analyse the interviews. The patient and their family were a key concern of all interviewees. Participants focused on processes including: giving care, making decisions, managing uncertainty and assimilating knowledge. These processes are mediated by 'phronesis' or practical wisdom. Within each of the processes (giving care, making decisions, managing uncertainty and assimilating knowledge), participants approached each patient as an individual, using experience, patient wishes, available resources, clinical knowledge and advice from colleagues to provide care. A generalised set of guidelines on managing urinary problems at the end of life would probably not be useful. There is uncertainty about what constitutes best practice in specific areas of continence care at the end of life such as indwelling urinary catheter insertion. A careful approach is needed to ensure that the intellectual and moral knowledge that constitutes practical wisdom is shared and developed throughout teams.


Subcellular partitioning of cadmium in the freshwater bivalve, Pyganodon grandis, after separate short-term exposures to waterborne or diet-borne metal.
The dynamics of cadmium uptake and subcellular partitioning were studied in laboratory experiments conducted on Pyganodon grandis, a freshwater unionid bivalve that shows promise as a biomonitor for metal pollution. Bivalves were collected from an uncontaminated lake, allowed to acclimate to laboratory conditions (≥25 days), and then either exposed to a low, environmentally relevant, concentration of dissolved Cd (5nM; 6, 12 and 24h), or fed Cd-contaminated algae (∼70nmol Cdg⁻¹ dry weight; 4×4h). In this latter case, the bivalves were allowed to depurate for up to 8 days after the end of the feeding phase. As anticipated, the gills were the main target organ during the aqueous Cd exposure whereas the intestine was the initial site of Cd accumulation during the dietary exposure; during the subsequent depuration period, the dietary Cd accumulated in both the digestive gland and in the gills. For the gills, the distribution of Cd among the subcellular fractions (i.e., granules>heat-denatured proteins (HDP)∼heat-stable proteins (HSP)>mitochondria∼lysosomes+microsomes) was insensitive to the exposure route; both waterborne and diet-borne Cd ended up largely bound to the granule fraction. The subcellular distribution of Cd in the digestive gland differed markedly from that in the gills (HDP>HSP∼granules∼mitochondria>lysosomes+microsomes), but as in the case of the gills, this distribution was relatively insensitive to the exposure route. For both the gills and the digestive gland, the subcellular distributions of Cd differed from those observed in native bivalves that are chronically exposed to Cd in the field - in the short-term experimental exposures of P. grandis, metal detoxification was less effective than in chronically exposed native bivalves.


Association of NM23 polymorphisms and clinicopathological features and recurrence of invasive pituitary adenomas.
Pituitary adenomas (PAs) are intracranial tumors, deriving from anterior pituitary cells. Previously, expression of non-metastasis-23 (NM23) gene has been shown to correlate with the progression of PAs. In this study, we aim to determine whether there is association between specific NM23 polymorphisms and invasive pituitary adenoma (IPA). Genotypes of rs2302254 and rs16949649 of NM23 were identified in the peripheral venous blood of patients by PCR-RLFP. Next, the correlation between specific genotypes of rs2302254 and rs16949649 and risk of IPA was investigated. Finally, the correlations between NM23 polymorphisms and tumor size, Ki67 LI and recurrence of IPA were analyzed with 3 to 24 months follow-up for the enrolled patients. We observed that the TT genotype at rs16949649 correlated closely with a high risk of IPA, while CC and CT genotypes reduced the risk of IPA. CC genotype at rs2302254 increased the risk of IPA, while CT and TT genotypes reduced the risk of IPA. Trs16949649Crs2302254 haplotype of NM23 was found to be a high-risk haplotype for IPA. TT genotype at rs16949649 and CC genotype at rs2302254 were associated with higher rates of tumors larger than 20 mm, Ki67 LI and tumor recurrence. Taken together, the present study provides evidence that NM23 polymorphisms are closely associated with the incidence and recurrence of IPA. Specifically, TT genotype at rs16949649 and CC genotype at rs2302254 are risk factors of IPA. NM23 polymorphisms could therefore be used as a reference for clinical diagnosis and prognosis of IPA.


[The challenge of language learning in nursing education].
For more than a century, French has lost its status as the international language of reference and the health system is no exception to this trend: English has become the official language of medical research, the number of non-English speaking patients is increasing and the desire of health students for international mobility is strong. In light of this, language learning during health studies is essential in that it enables future professionals to better understand the changes in society that have an impact on the health system.


[Prevention and therapy of cerebrospinal fluid leakage after translabyrinthine acoustic neuroma removal].
To evaluate the modified wound closure technique and other methods for preventing and treating the cerebrospinal fluid (CSF) leakage after removal of acoustic neuroma by translabyrinthine approach. In a series of 85 cases of acoustic neuroma surgery, two kinds of technique of wound closure, the traditional (as first group) and the modified (as second group), have been subsequently used to prevent CSF leakage. The incidences of CSF leak were analyzed respectively. Conservative and surgical treatments were applied to treatment the CSF leak. In the first group, the CSF leak was 19.5% (8/41), and that of second group was 2.3% (1/44). There was significant difference between them (P = 0.013). The CSF leak mainly occurred in large acoustic neuromas surgery with traditional wound closure technique. Among 9 cases of CSF leaks, 3 were controlled by conservative method, 5 by one single revision surgery and one by two revisions. The revision technique of wound closure could significantly reduce the incidence of CSF leakage after acoustic neuroma removal by translabyrinthine approach. The revision surgery is an effective method for stopping the CSF leak.


A retrospective review on feasibility and safety of a new pneumatic compression device for femoral arteriotomy hemostasis.
To report our initial experience on the technical feasibility and safety for hemostasis of a new pneumatic compression device in patients undergoing femoral arteriotomy. This study included 40 consecutive patients in whom hemostasis after transfemoral catheterization was readered by using a pneumatic compression device consisting of an inflatable bulb-containing main body and four pieces of supplementary tape. Medical records were retrospectively reviewed for outcomes and complications of hemostasis. Technical success was defined as achieving immediate hemostasis 10 minutes after applying the device over the arteriotomy sites, and clinical success was defined as the ability to ambulate after 4 hours of bed rest without any complications. Technical and clinical success was achieved in 38 (95%) and 37 (93%) patients, respectively. In two patients, hemostasis was achieved after conversion to manual compression. One patient required sand bag placement after removal of the device to control minimal oozing of blood. No patients had late complications. The new pneumatic compression device provides effective and safe hemostasis after transfemoral catheterization in selected patient populations.


Characterization of the complete mitochondrial genome of the Hypolimnas misippus Linnaeus 1764 (Lepidoptera: nymphalidae).
In this study, we sequenced the complete mitochondrial genome (mitogenome) of Hypolimnas misippus Linnaeus 1764, which is 15,283 bp in length, containing 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), two ribosomal RNA genes (rRNAs), and an adenine (A) + thymine (T)-rich (D-loop) region. The overall GC level is 19.8%. The phylogenetic position of H. misippus was evaluated using 48 previously published complete mitogenomes, and the results reveals that H. misippus is most closely related to H.bolina.


Minimal Important Difference for Physical Activity and Validity of the International Physical Activity Questionnaire in Interstitial Lung Disease.
The optimal method of physical activity measurement has not been determined in patients with fibrotic interstitial lung disease (ILD). To assess the validity, internal consistency, and responsiveness of the International Physical Activity Questionnaire long form (IPAQ-LF) and to estimate the minimal important difference (MID) for moderate to vigorous physical activity (MVPA) in patients with fibrotic ILD. This two-center prospective cohort study included a convenience sample of 111 outpatients with fibrotic ILD who wore waist and wrist ActiGraph accelerometers for 7 consecutive days, followed by self-administration of the IPAQ-LF. Both measurements were performed at baseline and 6-month follow-up. Spearman rank correlations were used to evaluate the IPAQ-LF validity in comparison to activity monitor data, lung function, step count, and quality of life. The internal consistency of the IPAQ-LF was determined using Cronbach's α. Self-reported changes in IPAQ-LF parameters were compared among tertiles of change measured by the waist activity monitor to assess the responsiveness of the IPAQ-LF after 6 months. Anchor- and distribution-based methods were used to estimate the MID for MVPA. Self-reported MVPA minutes, activity-related energy expenditure, sedentary time, and inactive time of the IPAQ-LF generally showed moderate to strong correlations with corresponding waist activity monitor data, step count, lung function, and quality of life. The Cronbach's α of the IPAQ-LF was 0.78. The IPAQ-LF was responsive at detecting increases in weekly MVPA and energy expenditure. The MIDs for MVPA were 8 to 26 and 13 to 58 min/wk using the anchor-based method for waist activity monitor and IPAQ-LF data, respectively. The distribution-based MID estimate for MVPA was 104 to 242 min/wk. The IPAQ-LF has acceptable validity and internal consistency for measuring daily physical activity in patients with fibrotic ILD. The IPAQ-LF was responsive at detecting increases in physical activity but limited in its ability to detect declines or changes in inactivity. Using an anchor-based approach, the MID for MVPA measured by a waist activity monitor is approximately 26 min/wk.


A central role for the acid sphingomyelinase/ceramide system in neurogenesis and major depression.
Major depressive disorder is a severe and chronic illness with high lifetime prevalence and a high incidence of suicide as the cause of death for patients with this diagnosis. Major depressive disorder is often treated with anti-depressants. Although these drugs have been used for many years, their exact mode of action is still unknown. It has been suggested that many anti-depressants act by increasing the concentrations of serotonergic transmitters in the synaptic space. However, recent studies have examined the effects of anti-depressants on neurogenesis in the hippocampus, the restoration of hippocampal neuronal networks that may be affected by major depression, and the regulation of the hypothalamic-pituitary-adrenal axis by immature neurons in the hippocampus. Here, we present and discuss a novel hypothesis suggesting that these events are regulated by the concentrations of sphingolipids, in particular ceramide, in the hippocampus. These concepts suggest that the acid sphingomyelinase/ceramide system plays a central role in the pathogenesis of major depression and may be a novel target for anti-depressants.


Photocatalytic activity of visible-light-driven L-Proline-TiO2/BiOBr nanostructured materials for dyes degradation: The role of generated reactive species.
L-Proline (2%)-TiO2/BiOBr (30%) nanocomposite was synthesized to obtain high photocatalytic performance in the visible light region and infrared radiation(IR) for methylene blue (MB) and congo red (CR) removal from the contaminated wastewater. L-Proline (2%)-TiO2/BiOBr (30%) photocatalyst with strong absorption near IR wavelength and high charge separation ability was fabricated for the first time. X-ray diffraction (XRD), Fourier transform infrared (FTIR), field-emission scanning electron microscope (FESEM)/Energy Dispersive X-ray (EDX), UV-Vis diffuse reflectance spectrum (DRS), photoluminescence (PL) and Brunauer-Emmett-Teller (BET) characterization techniques show that the visible driven nanocomposite was successfully synthesized. According to the UV-DRS analysis, the estimated band gaps for the L-proline (2%)-TiO2 and L-Proline (2%)-TiO2/BiOBr (30%) nanostructures were respectively 2.3 eV and 2.1 eV.The nanoparticles exhibited enhanced photocatalytic activity (93-100%) and high mineralization efficiency (71-89% TOC removal) for both the dyes. The best photocatalytic activity was achieved by adding 2 wt% of L-Proline and 30 wt% of BiOBr into TiO2 sol. Response surface methodology (RSM) was employed to find significant parameters and their optimum values for maximum degradation, which show pH, dye concentration, irradiation time, and catalyst dosage for both the dyes are significant. The best photocatalytic degradation efficiency was achieved at the optimum conditions of pH = 7.7, catalyst dosage = 0.71 g/L, irradiation time = 142 and dye concentration = 11 mg/L for MB. Scavenger study showed that •OH radicals are responsible for the degradation process.


Structure analysis of the Children's Eating Attitudes Test in overweight and at-risk for overweight children and adolescents.
In school-based samples of children, the Children's Eating Attitudes Test (ChEAT) has a four-factor structure; however, previous studies have not examined its factor structure in samples restricted to overweight youth. The ChEAT was administered to 220 overweight (BMI>or=95th percentile) and 45 at-risk for overweight (BMI 85th-<95th percentile) children and adolescents. Factors were identified by a principal component analysis with varimax rotation. ChEAT factor scores of children with BMI>or=85th percentile were contrasted with those of 152 non-overweight (BMI 5th to <85th percentile) children and adolescents. Factor analysis generated four subscales described as 'body/weight concern,' 'food preoccupation,' 'dieting,' and 'eating concern.' ChEAT total score, body/weight concern, and dieting subscale scores were positively related to BMI-Z and body fat mass (p's<.05). Compared to non-overweight children, overweight and at-risk for overweight children had higher ChEAT total (9.9+/-7.4 vs. 6.6+/-7.8, p<.001), body/weight concern (3.2+/-3.1 vs. 1.3+/-3.0, p<.001), and dieting (1.8+/-2.2 vs. .8+/-2.3, p<.001) subscale scores. The previously elucidated factor structure of the ChEAT was primarily supported in a sample of overweight children. The emergence of separate body/weight concern and dieting subscales may relate to these children's experiences with attempted weight reduction.


Imaging or trusting on surface anatomy? A comparison between fluoroscopic guidance and anatomic landmarks for femoral artery access in diagnostic cardiac catheterization. A randomized control trial.
We performed a randomized controlled trial to test the potential benefits of fluoroscopic-guided femoral artery puncture. Observational studies showed a consistent relationship between common femoral artery (CFA) and the head of femur. Fluoroscopy locating the femoral head may increase the accuracy of femoral puncture and consequently decrease the vascular complication. Despite these theoretical benefits, we have no sufficient evidence to verify its advantages. Patients undergoing diagnostic cardiac catheterization were randomized into fluoroscopic and anatomic method groups. Of total of 609 patients participated in this study, 305 and 304 patients were assigned to fluoroscopic and anatomic method groups, respectively. Fluoroscopy significantly increases the puncture over the femoral head (96.7 vs. 82.3 %, p value 0.001) and also the fluoroscopic method increased CFA puncture significantly (93.8 vs. 87.5 %, p value 0.012). The combined end point of "proper" femoral puncture (CFA puncture over the femoral head) was highly significant in our fluoroscopy-guided method (91.8 vs. 75.7 %, p value <0.0001). Hematoma was the only vascular complication trough the study (2.6 % of patients) but no significant difference was seen between the two groups. In conclusion, our study showed the efficacy of fluoroscopy in increasing the proper femoral artery puncture, and although it did not show significant improvement in vascular complications, the method should be regard as an accurate guide for femoral access.


Co-occurrence of congenital anomalies by maternal race/ethnicity among infants and fetuses with Down syndrome, 2013-2017: A U.S. population-based analysis.
Individuals with Down syndrome (DS) have a higher prevalence of additional congenital anomalies, especially cardiovascular defects, compared to the general population. Several reports have indicated that the prevalence of DS among live births varies by race and ethnicity within the United States. We aim to examine variations in co-occurring congenital anomalies by maternal race/ethnicity among infants and fetuses diagnosed with DS born during 2013-2017. State birth defect surveillance systems (N = 12) submitted data on infants and fetuses diagnosed with DS born during 2013-2017. We calculated the prevalence of co-occurring major and minor congenital anomalies, by organ system, and four selected cardiovascular birth defects, all stratified by maternal race/ethnicity. Among 5,836 cases of DS, 79.7% had one or more co-occurring congenital anomalies. There was a higher percentage of co-occurring congenital anomalies among infants and fetuses born to Hispanic mothers. The lowest percentage of co-occurring congenital anomalies, including three out of the four individual cardiovascular conditions examined, was among infants/fetuses born to non-Hispanic American Indian/Alaska Native mothers. We describe differences in DS co-occurrence with additional congenital anomalies among maternal racial/ethnic groups. These data may help focus future research on differences among racial/ethnic groups in the diagnosis and reporting of co-occurring congenital anomalies in infants/fetuses diagnosed with DS.


TssA from Aeromonas hydrophila: expression, purification and crystallographic studies.
TssA is a core subunit of the type VI secretion system, which is a major player in interspecies competition in Gram-negative bacteria. Previous studies on enteroaggregative Escherichia coli TssA suggested that it is comprised of three putative domains: a conserved N-terminal domain, a middle domain and a ring-forming C-terminal domain. X-ray studies of the latter two domains have identified their respective structures. Here, the results of the expression and purification of full-length and domain constructs of TssA from Aeromonas hydrophila are reported, resulting in diffraction-quality crystals for the middle domain (Nt2) and a construct including the middle and C-terminal domains (Nt2-CTD).


Microarray analysis of gender- and parasite-specific gene transcription in Strongyloides ratti.
The molecular mechanisms by which parasitic nematodes reproduce and have adapted to life within a host are unclear. In the present study, microarray analysis was used to explore differential transcription among the different stages and sexes of Strongyloides ratti, a parasitic nematode of brown rats. Specifically, gender-biased transcription between free-living females and free-living males, and parasitic-biased transcription between parasitic females and free-living females was determined. Of the estimated 3,688 distinct transcripts represented on the microarray, 743 (20%) exhibited male-biased transcription of >1.4-fold (2(0.5)), 689 (19%) female-biased transcription, 418 (11%) parasitic-biased transcription and 305 (8%) free-living-biased transcription. Among those transcripts that exhibited the highest levels of differential transcription, an orthologue of major sperm protein was identified in males, distinct aspartic protease orthologues in either parasitic or in free-living females, and orthologues of hsp-17 chaperone in parasitic females. These 3,688 transcripts were separated into 12 clusters, such that the pattern of transcription between life-stages and biological replicates was similar among transcripts within a cluster and dissimilar between clusters. Using annotation inferred from Caenorhabditis elegans, gene ontology terms over-represented in one or more clusters were identified and showed that female-biased transcription was associated with genes involved in reproductive processes and larval development, male-biased transcription was linked to genes involved in metabolism, and free-living-biased transcription related to genes involved in the regulation of body fluids and response to external stimulus. The association of gene ontology with parasite-biased transcription was less clear. The present findings for S. ratti provide a basis for a detailed exploration of differentially regulated molecules and might assist in the search for novel drug or vaccine targets in parasitic nematodes.


Blood vessel endothelia of the cerebral white matter of rats exposed to hypoxia. Karyometric and cytophotometric evaluation.
Hypoxic hypoxia is used as one of the models for examining the unfavourable effect of oxygen deficit on the nervous system. Since some morphological studies concerning the effect of hypoxia on the central nervous system have given consideration to perivascular lesion zones and glia alterations in the white matter, the present evaluation of the effect of hypoxia has been directed to vascular endothelia of the white matter. Examinations were conducted on adult rats of the Wistar strain which were exposed to acute hypoxia by being placed in a gas mixture containing 2% O2 or to moderate hypoxia - in a gas mixture containing 7% O2. Experimental animals were sacrificed 4 and 24 h after hypoxia and 14 and 60 d after hypoxia. The behaviour of vascular endothelia after hypoxia was evaluated by karyometric and cytophotometric methods. The measurements show an edema of endothelial nuclei in capillaries of the cerebral white matter of the rat in the first 24 h after hypoxia accompanied by nuclear chromatin index alterations proportional to the intensity of hypoxia. The measurements of endothelial nuclei 14 and 60 d after hypoxia show a development of a degenerative process in these nuclei, manifested by their decreasing size and by nuclear chromatin concentration in their central parts. The morphometric and cytophotometric examinations point to long-term alterations induced by hypoxic hypoxia.


[The Indeterminate Place of Property].
An increasing political contestation of the existing private-property order can currently be observed. With serious demands for expropriation, even outside marginalized splinter groups, a concept is returning that has largely disappeared from the focus of political theory. In this context, the article aims at a decidedly political-scientific examination of the legal institution of expropriation by locating the concept in the architecture of the democratic rule of law. Shifting between the poles of the constitutional guarantee of private property on the one hand and a potentiality of democratic contestation of the property order on the other, it is made clear that the concept of expropriation highlights the aporias of the democratic rule of law. The thesis is presented by means of a theoretical-historical contouring using the example of the intensive discussions on expropriation in the Weimar Republic and, in particular, with a more in-depth examination of the positions of Carl Schmitt and Otto Kirchheimer, which are subsequently figured as antipodes. While Schmitt seeks to make plausible a far-reaching rejection of expropriation potentials with a narrow concept of the rule of law, Kirchheimer focuses on an extensive interpretation of democratic power of disposition over the private-property order. The Weimar crisis years are examined as a kind of "laboratory" in order to profit from the extraordinary degree of crisis-induced searching and to work out a political science theoretical language for contemporary discussions of expropriation.