Headphone use and pedestrian injury and death in the United States: 2004-2011.
The association between distraction caused by cell phone use while driving and driver/passenger fatalities has been documented, but the safety risks associated with headphone use by pedestrians remains unknown. To identify and describe pedestrian-vehicle crashes in which the pedestrian was using headphones. A retrospective case series was conducted by searching the National Electronic Injury Surveillance System, US Consumer Product Safety Commission, Google News Archives and Westlaw Campus Research databases for reports published between 2004 and 2011 of pedestrian injuries or fatalities from crashes involving trains or motor vehicles. Cases involving headphones were extracted and summarised. The likelihood of headphone involvement was graded on a three-tier scale based on the information found in the article or report. There were 116 reports of death or injury of pedestrians wearing headphones. The majority of victims were male (68%) and under the age of 30 (67%). The majority of vehicles involved in the crashes were trains (55%), and 89% of cases occurred in urban counties. 74% of case reports stated that the victim was wearing headphones at the time of the crash. Many cases (29%) mentioned that a warning was sounded before the crash. The use of headphones with handheld devices may pose a safety risk to pedestrians, especially in environments with moving vehicles. Further research is needed to determine if and how headphone use compromises pedestrian safety.


Methods for characterizing ovarian and adrenal hormone variability and mood relationships in peripubertal females.
Peripubertal females are at elevated risk for developing affective illness compared to males, yet biological mechanisms underlying this sex disparity are poorly understood. Female risk for depression remains elevated across a woman's reproductive lifespan, implicating reproductive hormones. A sensitivity to normal hormone variability during reproductive transition events (e.g., perimenopause) precipitates affective disturbances in susceptible women; however, the extent of hormone variability during the female pubertal transition and whether vulnerability to peripubertal hormone flux impacts affective state change in peripubertal females has not been studied. 52 healthy peripubertal females (ages 11-14) provided 8 weekly salivary samples and mood ratings. 10 salivary ovarian and adrenal hormones (e.g., estrone, testosterone, dehydroepiandrosterone (DHEA)) were analyzed weekly for 8 weeks using an ultrasensitive assay to characterize the female peripubertal hormone environment and its association with affective state. Hormone variability indices, including standard deviation, mean squared and absolute successive differences of the 8 weekly measurements were analyzed by menarche status. Within-person partial correlations were computed to determine the strength of the relationship between weekly change in hormone level and corresponding mood rating for each participant. As expected, results indicated that hormone variability was greater for post- relative to pre-menarchal females and with advancing pubertal development, yet pregnenolone-sulfate and aldosterone did not differ by menarche status. Mood sensitivity to changes in estrone was exhibited by 57% of participants, whereas 37% were sensitive to testosterone and 6% were sensitive to DHEA changes. The present results offer novel evidence that a substantial proportion of peripubertal females appear to be mood sensitive to hormone changes and may inform future investigations on the biological mechanisms underlying hormone-induced affect dysregulation in peripubertal females.


Enhancement and mechanisms of iron-assisted anammox process.
Anaerobic ammonium oxidation (anammox) is a sustainable biological nitrogen removal technology that has limited large-scale applications owing to the low cell yield and high sensitivity of anammox bacteria (AnAOB). Fortunately, iron-assisted anammox, being a highly practical method could be an effective solution. This review focused on the iron-assisted anammox process, especially on its performance and mechanisms. In this review, the effects of iron in three different forms (ionic iron, zero-valent iron and iron-containing minerals) on the performance of the anammox process were systematically reviewed and summarized, and the strengthening effects of Fe (II) seem to be more prominent. Moreover, the detailed mechanisms of iron-assisted anammox in previous researches were discussed from macro to micro perspectives. Additionally, applicable iron-assisted methods and unified strengthening mechanisms for improving the stability of nitrogen removal and shortening the start-up time of the system in anammox processes were suggested to explore in future studies. This review was intended to provide helpful information for scientific research and engineering applications of iron-assisted anammox.


Acute and chronic toxicity study of the water accommodated fraction (WAF), chemically enhanced WAF (CEWAF) of crude oil and dispersant in the rock pool copepod Tigriopus japonicus.
We determined the toxicity of the water accommodated hydrocarbon fraction (WAF), two chemically enhanced WAFs (CEWAFs; CEWAF-C, Crude oil+Corexit 9500 and CEWAF-H, Crude oil+Hiclean) of crude oil and two dispersants (Corexit 9500 and Hiclean) to the rock pool copepod Tigriopus japonicus. In the acute toxicity test, Corexit 9500 was the most toxic of all the chemicals studied. The nauplius stage of T. japonicus was more susceptible to the toxic chemicals studied than the adult female. The toxicity data using the nauplius stage was then considered as baseline to determine the spiking concentration of chemicals for chronic toxicity tests on the copepod. As the endpoints in the chronic toxicity test, survival, sex ratio, developmental time and fecundity of the copepod were used. All chemicals used in this study resulted in increased toxicity in the F1 generation. The lowest-observed-adverse-effect (LOAE) concentrations of WAF, CEWAF-H, CEWAF-C, Hiclean and Corexit 9500 were observed to be 50%, 10%, 0.1%, 1% and 1%, respectively. The results in present study imply that copepods in marine may be negatively influenced by spilled oil and dispersant.


Self-Reported Transition Readiness of Adolescent Patients with Rheumatic Disease: Do the Parents Agree?
Our objective was to compare transition readiness assessment scores from adolescents with rheumatic disease with their parents and analyze their level of agreement. We found that adolescents and parents generally agree on the level of the transition readiness; however, there is occasional disagreement in specific domains.


A quality improvement initiative for neonatal hypoglycemia screening and management in a level III neonatal intensive care unit.
To bring screening and management of neonatal hypoglycemia in alignment with the 2011 AAP hypoglycemia clinical report METHODS: A multidisciplinary team developed a quality improvement initiative for neonatal hypoglycemia in neonates ≥35 weeks gestational age in a Level III neonatal intensive care unit between July 2020 and December 2021. A key driver diagram identified interventions for plan-do-study-act testing with corresponding measures to implement a hypoglycemia management protocol and improve adherence to AAP guidelines. Time to first blood glucose measurement increased from 49.8 to 122.7 min of life and time to first enteral feed decreased from 14.2 to 3.6 h of life. Neonates receiving intravenous dextrose decreased from 97.1 to 24.7% and discharge rates as a mother-neonate dyad increased from 35 to 62.4%. Adherence to the AAP guidelines improved during testing and implementation of a hypoglycemia protocol and was associated with an increased mother-neonate dyad discharge rate.


[The lifespan and Rubner constant at different temperatures in Drosophila melanogaster].
According to the Rubner's hypothesis, the total amount of oxygen consumed during life is constant for animals. This value is designated as the Rubner constant. Experimental data on the energetic exchange and life span in D. melanogaster allowed to conclude that the total oxygen consumption during the imaginal stage and during the whole ontogeny was not constant and changed under the influence of environmental temperature factor.


Genetic organization of Bungarus multicinctus protease inhibitor-like proteins.
The structural organization of the genes encoding Bungarus multicinctus protease inhibitor-like proteins (PILPs), PILP-1, PILP-2 and PILP-3, are reported in this study. Unlike PILP-2 and PILP-3, recombinant PILP-1 exhibited inhibitory activity on trypsin. PILP genes and B chain genes shared identical organization with three exons interrupted by two introns in similar positions. On the contrary, intron 1 of these genes had a similar size, a notable variation with the size of intron 2 was observed. It was found that two regions at the second intron of B1 chain and B2 chain genes were absent in that of PILP genes. Noticeably, intronic insertion in the second intron of B chain genes appeared in the promoter region of PILP-1 gene, but not in that of PILP-2 and PILP-3 genes. Comparative analyses of PILP genes and B chain genes showed that the protein-coding regions of the exons are more diverse than introns, except for in the signal peptide domain. These results suggest that PILP genes and B chain genes originate from a common ancestor, and that accelerated evolution may diversify PILP and B chain genes as that proposed for snake venom phospholipase A(2), neurotoxin and cardiotoxin genes.


Real-time metabolome profiling of the metabolic switch between starvation and growth.
Metabolic systems are often the first networks to respond to environmental changes, and the ability to monitor metabolite dynamics is key for understanding these cellular responses. Because monitoring metabolome changes is experimentally tedious and demanding, dynamic data on time scales from seconds to hours are scarce. Here we describe real-time metabolome profiling by direct injection of living bacteria, yeast or mammalian cells into a high-resolution mass spectrometer, which enables automated monitoring of about 300 compounds in 15-30-s cycles over several hours. We observed accumulation of energetically costly biomass metabolites in Escherichia coli in carbon starvation-induced stationary phase, as well as the rapid use of these metabolites upon growth resumption. By combining real-time metabolome profiling with modeling and inhibitor experiments, we obtained evidence for switch-like feedback inhibition in amino acid biosynthesis and for control of substrate availability through the preferential use of the metabolically cheaper one-step salvaging pathway over costly ten-step de novo purine biosynthesis during growth resumption.


Vitamin D in the Persian Gulf: integrative physiology and socioeconomic factors.
Countries of the Persian Gulf region--Bahrain, Iran, Iraq, Kuwait, Oman, Qatar, Saudi Arabia, and United Arab Emirates--have become increasingly modernized, resulting in a transformation of lifestyle based on technology, sedentary activity, lack of sunlight, and unhealthy dietary patterns. These factors have led to a higher prevalence not only of vitamin D undernutrition, but also chronic obesity, insulin resistance, prediabetes, and type 2 diabetes. This review explores the integrative physiologic effects of vitamin D with socioeconomic factors and propose a hypothesis-driven model for their contributions to obesity and diabetes in the Persian Gulf. Further research into these interactions may ultimately lead to novel preventive strategies and therapies for metabolic disorders in this geographic region.


Preparation and Fluorescent Labeling of Cell-Derived Micelles and Profiling on Glycan Microarrays.
Mammalian cell surface lectins mediate many important biological interactions which regulate physiological processes and therefore profiling mammalian cells on glycan microarray is of interest. However, many whole mammalian cells are not compatible with glycomics microarray formats and instead cell-derived micelles are prepared and profiled instead of whole cells as they can accurately represent the parental cell glycome. In this chapter, we describe the preparation of cell-derived micelles from mammalian cells, their labeling using a membrane-incorporating dye, and their profiling on a glycan microarray platform.


Prophylactic contralateral neck dissection has no advantage in patients with early stage HPV-positive tonsil cancer.
Patients with locally advanced HPV-positive tonsil cancer would benefit from prophylactic contralateral neck dissection (pCND). The aim of this study was to analyze rates of contralateral lymph node metastases (LNM) and their prognostic effects on locally advanced HPV-positive tonsillar squamous cell carcinoma. Medical records of 54 patients who underwent upfront primary surgery and pCND were retrospectively reviewed. Six (11.1%) patients had contralateral LNM in 54 locally advanced HPV-positive tonsil cancer. Of these, five patients had contralateral level II LNM and one patient had contralateral level II and III LNM. Contralateral LNM showed significant positive correlations with advanced T stage (p = .017) and the presence of extracapsular spread (p = .007). Contralateral lymph node metastasis had no significant association with five-year disease-specific survival. This study demonstrated no advantage in performing pCND in early stage HPV-positive tonsil cancer.


The human ovarian teratocarcinoma cell line PA-1 demonstrates a single translocation: analysis with fluorescence in situ hybridization, spectral karyotyping, and bacterial artificial chromosome microarray.
Cell lines derived from tumors contain numerous chromosomal aberrations and are the focus of study in tumor evolution. The ovarian teratocarcinoma cell line PA-1 demonstrates a single chromosomal aberration: a reciprocal t(15;20)(p11.2;q11.2). A complete molecular genetic analysis was undertaken to characterize this cell line. The PA-1 cell line was studied with fluorescence in situ hybridization (FISH), spectral karyotyping (SKY), bacterial artificial chromosome (BAC) microarray, and Western blotting. Amplification of 20q is frequently implicated in both breast and ovarian cancer; this region contains a number of oncogenes including MDM2, ZNF217, and the ovarian tumor marker WFDC2 (alias HE4). FISH revealed gene amplification of AIB1 (now known as NCOA3) but not STK15 (now known as AURKA). Immunoblot analysis demonstrated 3.6-fold overexpression of the AIB1 protein product, but no elevation of the STK15. BAC cancer gene microarray analysis showed gene amplification of > or =1.20 for five oncogenes. The presence of a consistent single change in PA-1, the t(15;20)(p11.2;q11.2), suggests that the aberration is significant with respect to the transformation status of the cell line. This translocation appears to cause overexpression of AIB1 (and perhaps other proteins), which may provide an immortalizing effect on this cell line.


Incidence of vaginal intraepithelial neoplasia after hysterectomy for cervical intraepithelial neoplasia: a retrospective study.
Hysterectomy with concomitant cervical intraepithelial neoplasia (CIN), is often considered a definitive treatment for CIN, but development of subsequent vaginal intraepithelial neoplasia (VAIN) is known to range from 0.9% to 6.8%. In a retrospective analysis of 3030 women with CIN2+ without history of VAIN in the University Hospital Gasthuisberg, Leuven, Belgium, from January 1989 until December 2003, we identified 125 women who underwent a hysterectomy within 6 months after diagnosis of CIN2+ and reviewed their postoperative Papanicolaou smears. Thirty-one patients (24.8%) were lost to follow-up. Seven of the 94 women in the follow-up group (7.4%) developed VAIN2+, of which 2 were invasive vaginal cancers. Median interval between hysterectomy and diagnosis of VAIN2+ was 35 months (5-103 months). Women with recurrence were significantly older (P = .003). Hysterectomy may not be considered as a definitive therapy for CIN2+ because the incidence rate of subsequent VAIN2+ is as high as 7.4%.


Local delivery of siRNA using a biodegradable polymer application to enhance BMP-induced bone formation.
Small interfering RNA (siRNA) is useful tool for specific and efficient knockdown of disease-related genes. However, in vivo applications of siRNA are limited due to difficulty in its efficient delivery to target cells. In this study, we investigated the efficacy of a biodegradable hydrogel, poly-d,l-lactic acid-p-dioxanone-polyethylene glycol block co-polymer (PLA-DX-PEG), as a siRNA carrier. PLA-DX-PEG pellets with or without fluorescein-labeled dsRNA were implanted into mouse dosal muscle pouches. The cellular uptake of dsRNA surround the polymer was confirmed by fluorescent microscopy. The fluorescence intensity was dose-dependent of the dsRNA, and exhibited a time-dependent decrease. To investigate its biological efficiency, noggin (antagonoist to BMPs) gene-silencing with siRNA (siRNA/Noggin) was examined by the amount of suppression of BMP-2-induced noggin expression and the level of performance of BMP, indicated by ectopic bone formation. Noggin gene expression induced by BMP-2 was suppressed by addition of siRNA/Noggin to the implant, and the ectopic bone formation induced by implants with both BMP-2 and siRNA/Noggin was significantly greater than those induced by implants with BMP-2 alone. These results indicate the efficacy of local delivery of siRNAs by PLA-DX-PEG polymer, which intensified bone-inducing effects of BMP and promoted new bone formation by suppressing gene expression of Noggin.


C-reactive protein, lipoprotein(a), homocysteine, and male sex contribute to carotid atherosclerosis in peritoneal dialysis patients.
In patients with end-stage renal disease, the morbidity and mortality of cardiovascular disease are substantially greater than in the general population. Advancement in understanding the pathogenesis of atherosclerotic vascular disease suggests a central role of inflammation in atherogenesis. However, clinical data evaluating the role of inflammation in atherogenesis are sparse in peritoneal dialysis (PD) patients. We measured serum C-reactive protein (CRP), intact parathyroid hormone, lipoprotein(a) [Lp(a)], interleukin-1 receptor antagonist (IL-1Ra), tumor necrosis factor soluble receptor (TNF-sR), fibrinogen, and plasma homocysteine (Hcy), as well as intima-media thickness (IMT) and number of atherosclerotic plaques (plaque score [PS]) in the carotid arteries by means of carotid B-mode ultrasonography in 59 PD patients (35 men, 24 women; mean age, 52.4 years; average dialysis period, 36 months). All patients had chronic glomerulonephritis. Sixty-eight percent of PD patients had at least 1 plaque. Serum CRP level was greater than the upper limit of the normal range in 52.5% of patients. Compared with PD patients with normal CRP levels, concentrations of such proinflammatory cytokines as IL-1Ra and TNF-sR, Lp(a), and Hcy were increased in PD patients with elevated CRP levels. However, no differences in plasma fibrinogen and intact parathyroid hormone levels were found between PD patients with increased and normal CRP levels. In a multiple regression model, age, male sex, CRP level, and Lp(a) level were independent predictors of IMT. Similarly, male sex, CRP level, Lp(a) level, and Hcy level were independent correlates of PS. This study suggests that Lp(a) and Hcy levels and male sex, and especially CRP level, have an important role in carotid atherosclerosis in PD patients.


Hidden multiplicity in exploratory multiway ANOVA: Prevalence and remedies.
Many psychologists do not realize that exploratory use of the popular multiway analysis of variance harbors a multiple-comparison problem. In the case of two factors, three separate null hypotheses are subject to test (i.e., two main effects and one interaction). Consequently, the probability of at least one Type I error (if all null hypotheses are true) is 14 % rather than 5 %, if the three tests are independent. We explain the multiple-comparison problem and demonstrate that researchers almost never correct for it. To mitigate the problem, we describe four remedies: the omnibus F test, control of the familywise error rate, control of the false discovery rate, and preregistration of the hypotheses.


Biomedical named entity recognition with the combined feature attention and fully-shared multi-task learning.
Biomedical named entity recognition (BioNER) is a basic and important task for biomedical text mining with the purpose of automatically recognizing and classifying biomedical entities. The performance of BioNER systems directly impacts downstream applications. Recently, deep neural networks, especially pre-trained language models, have made great progress for BioNER. However, because of the lack of high-quality and large-scale annotated data and relevant external knowledge, the capability of the BioNER system remains limited. In this paper, we propose a novel fully-shared multi-task learning model based on the pre-trained language model in biomedical domain, namely BioBERT, with a new attention module to integrate the auto-processed syntactic information for the BioNER task. We have conducted numerous experiments on seven benchmark BioNER datasets. The proposed best multi-task model obtains F1 score improvements of 1.03% on BC2GM, 0.91% on NCBI-disease, 0.81% on Linnaeus, 1.26% on JNLPBA, 0.82% on BC5CDR-Chemical, 0.87% on BC5CDR-Disease, and 1.10% on Species-800 compared to the single-task BioBERT model. The results demonstrate our model outperforms previous studies on all datasets. Further analysis and case studies are also provided to prove the importance of the proposed attention module and fully-shared multi-task learning method used in our model.


Advanced diabetic glomerulopathy. Quantitative structural characterization of nonoccluded glomeruli.
Quantitative ultrastructural data were obtained from kidney biopsy material of 12 long-term insulin-dependent diabetics. All patients had overt diabetic nephropathy with increased urinary albumin excretion and reduced glomerular filtration rate. Renal clearance of 51Cr-EDTA was in the range of 16-50 ml X min-1 X 1.73 m-2. All patients received antihypertensive treatment. A combined light- and electron-microscope study was performed. A significant proportion of the glomeruli was totally occluded (mean 36%, range 24-67%). Structural data presented relate only to the open, still-functioning glomeruli. Comparison with data previously obtained showed that the thickness of the peripheral basement membrane [647 nm, coefficient of variation (C.V.) 0.22] was more than twice the normal value (310 nm, C.V. 0.08); the width of epithelial foot processes (352 nm, C.V. 0.07) was significantly greater than in normal biopsies (224 nm, C.V. 0.06); and the mean volume of the open glomeruli was markedly increased compared with normal and clearly exceeded that in the early diabetic hypertrophy. Total mesangial volume and total basement membrane material per open glomerulus were increased by 277 and 614%, respectively. However, capillary length and surface per open glomerulus were similar to those observed in early diabetic hypertrophy. These findings suggest that a late glomerular hypertrophy with preservation of capillary surface occurs as a compensatory phenomenon, prolonging renal survival for diabetic nephropathy patients.


Local and diffuse synaptic actions of GABA in the hippocampus.
In the CNS, gamma-aminobutyric acid (GABA) acts as an inhibitory transmitter via ligand-gated GABAA receptor channels and G protein-coupled GABAB receptors. Both of these receptor types mediate inhibitory postsynaptic transmission in the hippocampus. In addition to these direct postsynaptic actions, GABAB receptor agonists inhibit excitatory transmission through presynaptic receptors on excitatory afferent terminals. However, a physiological role for the GABAB receptors on excitatory nerve endings has not been established. In this study, we have found a brief, heterosynaptic depression of excitatory synaptic transmission in the CA1 region of the hippocampal slice following short-lasting repetitive stimulation and determined that this inhibition is mediated by presynaptic GABAB receptors. The inhibition of GABA uptake greatly enhanced both the presynaptic action of GABA and the slow GABAB-mediated inhibitory postsynaptic current. Transmitter uptake was also found to regulate the "spill-over" of GABA at conventional GABAA synapses. These results suggest that uptake mechanisms restrict the spatial range of both point-to-point synaptic transmission mediated by GABA and its action at a distance.


Heritable gene silencing in Drosophila using double-stranded RNA.
RNA-mediated interference (RNAi) is a recently discovered method to determine gene function in a number of organisms, including plants, nematodes, Drosophila, zebrafish, and mice. Injection of double-stranded RNA (dsRNA) corresponding to a single gene into organisms silences expression of the specific gene. Rapid degradation of mRNA in affected cells blocks gene expression. Despite the promise of RNAi as a tool for functional genomics, injection of dsRNA interferes with gene expression transiently and is not stably inherited. Consequently, use of RNAi to study gene function in the late stages of development has been limited. It is particularly problematic for development of disease models that reply on post-natal individuals. To circumvent this problem in Drosophila, we have developed a method to express dsRNA as an extended hairpin-loop RNA. This method has recently been successful in generating RNAi in the nematode Caenorhabditis elegans. The hairpin RNA is expressed from a transgene exhibiting dyad symmetry in a controlled temporal and spatial pattern. We report that the stably inherited transgene confers specific interference of gene expression in embryos, and tissues that give rise to adult structures such as the wings, legs, eyes, and brain. Thus, RNAi can be adapted to study late-acting gene function in Drosophila. The success of this approach in Drosophila and C. elegans suggests that a similar approach may prove useful to study gene function in higher organisms for which transgenic technology is available.


Ward Climate Within a High Secure Forensic Psychiatric Hospital: Perceptions of Patients and Nursing Staff and the Role of Patient Characteristics.
Within this study the relationship between patient characteristics (age, length of stay, risk, psychopathy) and individual perceived ward climate (n=83), and differences between staff's and patient perceptions of climate (n=185) was investigated within a high secure forensic hospital. Results show that therapeutic hold was rated higher among staff compared to patients, while patients held a more favorable view on patient cohesion and experienced safety. Furthermore, patient characteristics (age, risk and psychopathy) were found to be related with individual ratings of ward climate. The findings underline the importance of assessing ward climate among both patients and staff in clinical practice.


Validity of electrocardiographic classification of left ventricular hypertrophy across adult ethnic groups with echocardiography as a standard.
To assess the validity of the electrocardiogram (ECG) as a diagnostic tool for left ventricular hypertrophy (LVH) for different ethnic groups with echocardiography as a standard. Systematic review of the literature using the Cornell and Sokolow-Lyon voltage criteria for LVH. Five studies were identified. Pooled data from these studies demonstrated low sensitivity using both types of ECG criteria for white and African-origin groups, but with slightly higher sensitivity values for the African-origin group (Cornell, 31.2%; 95% confidence interval [CI], 28%-34.8%; Sokolow-Lyon, 32.9%; 95% CI, 29.5%-36.4%) compared with the white group (Cornell, 26.5%; 95% CI, 25.2%-27.8%; Sokolow-Lyon, 18.2%; 95% CI, 17.2%-19.3%). Specificity was high using both types of criteria in the white group (Cornell, 87.4%; 95% CI, 86.4%-88.4%; Sokolow-Lyon, 88.9%; 95% CI, 88%-90%) but was much lower in the African-origin group using the Sokolow-Lyon criteria (72.1%; 95% CI, 68.7%-75.3%). Specificity was high however for the African-origin group using the Cornell criteria (86.2%, 95% CI, 83.4%-88.5%). Both types of criteria are more sensitive in African-origin populations. The Sokolow-Lyon criteria are less specific for LVH in people of African origin. The evidence favors the Cornell criteria in research and service contexts involving African-origin and white populations. Further research is needed to adapt ECG criteria to take into account ethnicity to a greater degree. The issue needs to be studied in a broader range of ethnic groups.


Nasal foreign bodies: a review of management strategies and a clinical scenario presentation.
We report a case of a toothbrush head lodged into the nasal cavity, which required an external rhinoplasty for retrieval. A review of the literature on management strategies in case of nasal foreign bodies is presented.


Virus capsid expansion driven by the capture of mobile surface loops.
The capsids of tailed-DNA bacteriophages first assemble as procapsids, which mature by converting into a new form that is strong enough to contain a densely packed viral chromosome. We demonstrate that the intersubunit crosslinking that occurs during maturation of HK97 capsids actually promotes the structural transformation. Small-angle X-ray scattering and crosslinking assays reveal that a shift in the crosslink pattern accompanies conversion of a semimature particle, Expansion Intermediate-I/II, to a more mature state, Balloon. This transition occurs in a switch-like fashion. We find that crosslink formation shifts the global conformational balance to favor the balloon state. A pseudoatomic model of EI-I/II derived from cryo-EM provides insight into the relationship between crosslink formation and conformational switching.


The thymidine kinase gene of herpes simplex virus type 1: cell-free protein synthesis and substrate specificity studies.
The HSV thymidine kinase genetic system has a number of advantages for the study of virus and cell genetics. Both forward and reverse mutants are readily selected. The enzyme can be assayed directly in the presence of the cell TK by the choice of the appropriate substrate, for example, 125IdC. The gene product, HSV TK, can be identified by SDS-polyacrylamide gel electrophoresis and mutants can be found with alterations in the electrophoretogram. The in vitro synthesis of HSV TK in response to HSV mRNA has been achieved and can be used to analyse specific mutant virus.


The impact of storage buffer and storage conditions on fecal samples for bacteriophage infectivity and metavirome analyses.
There is an increasing interest in investigating the human gut virome for its influence on the gut bacterial community and its putative influence on the trajectory towards health or disease. Most gut virome studies are based on sequencing of stored fecal samples. However, relatively little is known about how conventional storage buffers and storage conditions affect the infectivity of bacteriophages and influence the downstream metavirome sequencing. We demonstrate that the infectivity and genome recovery rate of different spiked bacteriophages (T4, c2 and Phi X174) are variable and highly dependent on storage buffers. Regardless of the storage temperature and timespan, all tested phages immediately lost 100% (DNA/RNA Shield) or more than 90% (StayRNA and RNAlater) of their infectivity. Generally, in SM buffer at 4 °C phage infectivity was preserved for up to 30 days and phage DNA integrity was maintained for up to 100 days. While in CANVAX, the most effective buffer, all spiked phage genomes were preserved for at least 100 days. Prolonged storage time (500 days) at - 80 °C impacted viral diversity differently in the different buffers. Samples stored in CANVAX or DNA/RNA Shield buffer had the least shifts in metavirome composition, after prolonged storage, but they yielded more contigs classified as "uncharacterised". Moreover, in contrast to the SM buffer, these storage buffers yielded a higher fraction of bacterial DNA in metavirome-sequencing libraries. We demonstrated that the latter was due to inactivation of the DNases employed to remove extra-cellular DNA during virome extraction. The latter could be partly avoided by employing additional washing steps prior to virome extraction. Fecal sample storage buffers and storage conditions (time and temperature) strongly influence bacteriophage infectivity and viral composition as determined by plaque assay and metavirome sequencing. The choice of buffer had a larger effect than storage temperature and storage time on the quality of the viral sequences and analyses. Based on these results, we recommend storage of fecal virome samples at in SM buffer at 4 °C for the isolation of viruses and at - 80 °C for metagenomic applications if practically feasible (i.e., access to cold storage). For fecal samples stored in other buffers, samples should be cleared of these buffers before viral extraction and sequencing. Video Abstract.


Working together to promote and celebrate the diversity of nursing.
This year has been particularly challenging for nurses around the world. As the commemorations take place for International Nurses Day on 12 May, the Chief Nursing Officer for Scotland and Chief Nursing Officer for Wales share their priorities and hopes for the coming year.


Density estimation applications for outlier detection.
Nonparametric estimates of joint, conditional and marginal probability densities can be used to estimate the relative probability of a data point's recurrence. Outlier, unusual or abnormal values of a random variate tend to be those which are unlikely to recur. As part of an interactive graphical system, a procedure has been implemented which enables a biomedical researcher to view both the estimated probability and the numerical value of a data point's coordinates. This display circumvents the problem of interpreting a normal range in two or more dimensions and can thus be more easily generalized than most alternative outlier detection procedures.


Multimodal therapy in children and adolescents with newly diagnosed atypical teratoid rhabdoid tumor: individual pooled data analysis and review of the literature.
Atypical teratoid rhabdoid tumour (ATRT) is a malignant tumour of the central nervous system with a dismal prognosis. There is no consensus on optimal treatment and different multimodal strategies are currently being used in an attempt to improve outcomes. To evaluate the impact of high-dose chemotherapy followed by autologous stem-cell rescue (HD48 SCR), radiotherapy (RT) at first line, intrathecal chemotherapy (IT) and extent of surgical resection upon recurrence-free survival (RFS) and overall survival (OS). An online database search identified prospective and retrospective studies focused on the treatment of children and adolescents with newly diagnosed ATRT. Clinical, therapeutic and outcome data were extracted and an individual pooled data analysis was conducted. Out of 389 publications, 12 manuscripts were included in our review. Data from 332 patients were analysed. Median age at diagnosis was 37 months (range 1-231). HD-SCR, RT and IT had been administered to 28.6% (58/203), 49.6% (118/238) and 21% (65/310) of the patients, respectively. Gross total resection (GTR) had been achieved in 46.5% (152/327) of the cases. In the multivariate analysis, hazard ratios (95% Confidence Interval) for HD-SCR were: RFS-HR = 0.570 (0.357-0.910) p = 0.019, and OS-HR = 0.388 (0.214-0.704) p = 0.002; and for RT: RFS-HR = 0.551 (0.351-0.866) p = 0.01, and OS-HR = 0.393 (0.216-0.712) p = 0.002. IT and GTR were not significantly associated with improved RFS or OS in the multivariate analysis. In our pooled data review, HD-SCR and RT at first line were associated with improved outcomes in children and adolescents with newly diagnosed ATRT.


Fractionated stereotactic radiotherapy for the treatment of acoustic neuromas: preliminary results.
To evaluate the efficacy and toxicity of fractionated, stereotactic radiotherapy (SRT) for acoustic neuromas. Twelve patients with acoustic neuroma were treated with SRT between June 1992 and October 1994. Follow-up ranged from 16-44 months. Patient age ranged from 27-70 (median: 45). Eight patients were treated with primary SRT and four patients were treated after primary surgical intervention for recurrent [3] or persistent [1] disease. Tumor volumes were 1.2-18.4 cm3 (median: 10.1 cm3). Collimator sizes ranged from 30-50 mm (median: 37.5). Tumors received 1.8 Gy/day normalized to the 95% isodose line. Patients received a minimum prescribed dose of 54 Gy in 27-30 fractions over a 6-week period. After a median follow-up of 26.5 months, local control was obtained in 12 out of 12 lesions. Tumor regression was noted in three patients, and tumor stabilization was found in the remaining nine patients. No patient developed a new cranial nerve deficit. One patients developed worsening of preexisting Vth cranial neuropathy and another experienced a decrease in hearing. However, all nine patients with useful hearing prior to SRT maintained useful hearing at last follow-up. Stereotactic radiotherapy provided excellent local control without new cranial nerve deficits. These results must be viewed as tentative in nature because of the small number of patients and the short median follow-up period.


Pathogenic carrier rate in diabetes mellitus.
Thirty patients with diabetes mellitus were compared in terms of carrier rate of four pathogens to a group of matched controls. The diabetics were found to have a significantly increased carrier rate (p less than 0.005). When the blood glucose level was used as an indicator of control an increased rate was found in those with the poorest control (p less than 0.0005). An increased carriage of Candida albicans might be attributed to hypovitaminosis A and its effect on mucous membranes and the skin. Ten percent of diabetics were carrying beta-hemolytic group A streptococci. In a future study these patients will be checked for persistence of these organisms as well as to see if the strains are of the nephritogenic type. A significantly increased carriage rate in diabetes of coagulase-positive Staphylococcus aureus was found. These findings suggest an additional risk factor in the outpatient diabetic population.


Prognostic value of early electrophysiologic studies for ventricular tachycardia recurrence in patients with coronary artery disease treated with amiodarone.
Amiodarone was used in 86 patients with ventricular tachycardia (VT) (67 patients) or ventricular fibrillation (19 patients) secondary to coronary artery disease. The mean +/- standard deviation left ventricular ejection fraction was 30 +/- 12% (range 8 to 65%). Prior trials with 4 +/- 1.2 alternate antiarrhythmic agents had been unsuccessful. Amiodarone was loaded at dosages of 1,200 to 1,800 mg/day, with maintenance dosages of 400 to 600 mg/day. Drug efficacy was evaluated by programmed stimulation at 10 to 14 days in 68 patients. In 38 patients sustained VT or ventricular fibrillation was inducible (group I), whereas 30 patients (group II) had either no inducible VT (8) or had nonsustained VT induced (22). Holter monitoring was used to assess drug efficacy in 18 patients (group III). All patients were evaluated at 3- to 6-month intervals with Holter monitors for efficacy and a standard protocol for toxicity. During a long-term follow-up of 18 +/- 16 months, sudden death occurred in 5 patients and nonfatal arrhythmia recurrences were detected in 16. The actuarial probability of freedom from fatal and nonfatal arrhythmia recurrences at 24 months was 0.52 for group I, 0.97 for group II and 0.68 for group III. The mode of induction, rate change or hemodynamic tolerance of the induced ventricular tachycardia did not predict arrhythmia recurrence. Among the clinical variables analyzed, only an ejection fraction of less than or equal to 30% was identified as a significant predictor of arrhythmia recurrence. Nonsudden cardiac death occurred in 21 patients, including 19 from heart failure and 2 from myocardial infarction. Noncardiac death occurred in 7 patients.(ABSTRACT TRUNCATED AT 250 WORDS)


Factor XIII Val34Leu mutation accelerates the development of fibrosis in patients with chronic hepatitis B and C.
There is considerable variation in liver fibrosis stage and progression to cirrhosis among patients with chronic hepatitis B (CHB) or C (CHC). Coagulation pathway activity due to genetic variations could influence the rate of fibrosis. We investigated thrombotic risk factors and their association with the extent and progression of fibrosis in CHB or CHC patients. In total, 194 patients with CHB (n = 88) or CHC (n = 106) were included. Data on demographic and laboratory findings were collected. Liver biopsies were evaluated according to the Ishak classification system. Fibrosis progression rate (FPR), defined as ratio of fibrosis score to duration of infection, was determined for 131 patients. Prevalence of factor V Leiden, prothrombin G20210A, plasminogen activator inhibitor type-1 (PAI-1) 4G/5G and factor XIIIA Val34Leu mutations was evaluated. Heterozygosity for factor V Leiden, prothrombin G20210A, PAI-1 4G/5G and factor XIIIA Val34Leu mutations was present in 3.1%, 2.1%, 49% and 28% of the patients, respectively. Factor XIII Val34Leu mutation was a risk for enhanced FPR (odds ratio 4.7; P = 0.01). In patients with both factor XIII Val34Leu and PAI-1 4G/5G mutations the risk of an accelerated FPR was further increased (odds ratio 5.0; P = 0.02). Mutations of the other thrombotic genes were not significantly associated with fibrosis stage and FPR. Our data show that factor XIII Val34Leu mutation alone or in combination with PAI-1 4G/5G mutation is a risk factor for an increased rate of liver fibrosis development in patients with CHB or CHC.


Validating ASHS-T1 automated entorhinal and transentorhinal cortical segmentation in Alzheimer's disease.
The current study aimed to validate entorhinal and transentorhinal cortical volumes measured by the automated segmentation tool Automatic Segmentation of Hippocampal Subfields (ASHS-T1). The study sample comprised 34 healthy controls (HCs), 37 individuals with amnestic mild cognitive impairment (aMCI), and 29 individuals with Alzheimer's disease (AD) dementia from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Entorhinal and transentorhinal cortical volumes were assessed using ASHS-T1, manual segmentation, as well as a widely used automated segmentation tool, FreeSurfer v6.0.1. Mean differences, intraclass correlation coefficients, and Bland-Altman plots were computed. ASHS-T1 tended to underestimate entorhinal and transentorhinal cortical volumes relative to manual segmentation and FreeSurfer. There was variable consistency and low agreement between ASHS-T1 and manual segmentation volumes. There was low-to-moderate consistency and low agreement between ASHS-T1 and FreeSurfer volumes. There was a trend toward higher consistency and agreement for the entorhinal cortex in the aMCI and AD groups compared to the HC group. Despite the differences in volume measurements, ASHS-T1 was sensitive to entorhinal and transentorhinal cortical atrophy in both early and late disease stages. Based on the current study, ASHS-T1 appears to be a promising tool for automated entorhinal and transentorhinal cortical volume measurement in individuals with likely underlying AD.


Reporting both length and mass values to quantify body size for amphibians and reptiles.
Body size is perhaps the most important trait for organism biologists, as it is associated with a myriad of ecological, evolutionary, behavioral, morphological, physiological and life-history aspects (e.g., rates of molecular evolution, metabolic rates, predation, reproduction), and with extinction risk. There are, however, several measures commonly used to quantify organism body size. Within ectothermic tetrapods, the most common measures include snout-vent length (SVL, mostly in lizards), and total length (TL, in most snakes). In endotherms, however, and especially in mammals, body mass is the most common measure of size.


Capsaicin-induced central facilitation of a nociceptive flexion reflex in humans.
The effect of selective activation of nociceptive primary afferent fibers by capsaicin on a nociceptive lower limb flexion reflex was studied in healthy human subjects. Capsaicin (1%) applied topically to the skin produced a burning spontaneous pain sensation and allodynia in the treated region and in its immediate vicinity. Capsaicin applied to the distal innervation area of the sural or saphenous nerve produced a significant decrease of the threshold for the nociceptive limb flexion reflex induced by electric stimulation of the proximal sural nerve trunk, and this threshold decrease was rapidly attenuated by a cool compress concomitantly with the attenuation of the capsaicin-induced spontaneous pain. The latency of the flexion reflex response was not changed by capsaicin. The non-nociceptive H-reflex was not modified by capsaicin. It is concluded that a selective activation of nociceptive primary afferent fibers of the skin by capsaicin produces a central facilitation of a nociceptive flexion reflex in humans. This facilitation is selective on the nociceptive reflex and depends, at least partly, on the on-going afferent barrage in C-fibers.


An adaptable microvalving system for on-chip polymerase chain reactions.
On-chip genetic analysis systems are beginning to provide a viable alternative to conventional gene profiling and amplification devices, through minimal reagent use, high detection resolution, and the potential for high-throughput parallel testing of the genetic material, even from single cells. Despite the advantages, there are many difficulties inherent in creating an integrated microfluidic diagnostic platform. One major challenge is the accurate control and manipulation of fluid, and particularly the immobilization of reaction mixtures during heating phases of polymerase chain reactions (PCR). In this paper we present a pumping and valving system based on the use of three servomotor-controlled valve fingers that actuate microchannels within a poly-dimethylsiloxane (PDMS) fluidic chip. We characterize the valving ability of the system in terms of fluid loss and show the successful fluid retention of the system over 35-cycle PCR runs at temperatures of up to approximately 96 degrees C. In addition, we demonstrate the system's ability to perform PCR by successfully amplifying a sample of beta2 microglobulin transcript obtained from the peripheral blood of a patient with multiple myeloma. This work has proven to be a successful approach to multi-use valving and a viable method of alleviating the fluid control difficulties inherent in performing a PCR reaction in an on-chip environment. In addition, it opens the door for further automation and integration with other chip-based genetic analysis platforms.


CAP sleep in insomnia: new methodological aspects for sleep microstructure analysis.
This work aims to propose new methodologies for the quantitative characterization of insomnia. Sleep microstructure, as expressed by Cyclic Alternatic pattern (CAP) sleep, is studied and differences between normal sleepers and insomniacs are investigated. The dynamic in the structure of CAP activation events is studied by use of wavelet analysis and the content of events, i.e. EEG dynamics, is studied in terms of complexity analysis. Both in structure and content, features exhibiting statistically significant differences are proposed, opening new perspectives for the understanding and the quantitative characterization of sleep and its disorders.


Chondroitin sulfate-based anti-inflammatory macromolecular prodrugs.
Macromolecular prodrugs of three non-steroidal anti-inflammatory drugs (NSAIDs), ibuprofen, ketoprofen, and naproxen, were prepared by the covalent attachment of the drugs onto chondroitin sulfate (ChS) using PEG 1000 as a spacer. Drug-PEG adducts were synthesized using 1,1'-carbonyl diimidazole as a coupling agent in dimethyl sulfoxide, followed by the reaction with ChS in highly dilute aqueous solution at pH 6.8 via N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDAC) as a conjugation agent. The drug-ChS conjugates were confirmed by FTIR, 1H NMR and 13C NMR and the molar percent of drug substitution onto ChS was characterized by 1H NMR using the peak areas of the three protons of -PhiCHCH3 on the drugs to those of -NHCOCH3 on ChS. All drug-ChS conjugates are water-soluble. The release amounts of the free drugs from their corresponding drug-ChS conjugates were evaluated in the presence or absence of either esterase or chondroitinase, and the both enzymes in pH 7.4 Tris-buffer solutions at 37 degrees C by high performance liquid chromatography (HPLC). Keto-ChS conjugates released approximately 100% ketoprofen within 12h in the presence of esterase, but the combination with chondroitinase did not accelerate the release rate. The degradation of Keto-ChS conjugates by chondroitinase was confirmed by gel permeation chromatography (GPC). The Keto-ChS conjugates still retained the enzymatic recognition even at the substitution of ketoprofen as high as 56 mol%. The inhibition percent of carrageenan-induced edema of Keto-ChS-56 was comparable to that of a simple blend of ChS and ketoprofen, suggesting that biologically active ChS and ketoprofen could be liberated from the conjugate.


Clinical characteristics of diabetic patients with serious pedal infections.
The clinical characteristics of 55 diabetic patients referred for treatment of serious pedal infections were surveyed. These patients had been infected for 22.5 +/- 5.0 weeks prior to referral. A majority had received therapy with oral antibiotics and approximately one third had received no antibiotic therapy. The average age of the patients was 53.5 years; average duration of disease, 18 years; and mean weight, 135% of ideal. All had poor glycemic control, as judged by hemoglobin A1c determinations. The patients had a high prevalence of diabetic complications, particularly peripheral neuropathy and nephropathy. Approximately 69% were hypertensive. Although their corrected ESRs were elevated, mean total WBC counts were not. A majority of the patients had zinc deficiency. Most of their infections involved multiple organisms, particularly staphylococcus species, enterococcus, and gram-negative aerobes. These observations suggest that the clinical characteristics of these patients in part explain the difficult nature of their infections and argue the need for early, aggressive antibiotic therapy.


Correction to "New Type of Similar Material for Simulating the Processes of Water Inrush from Roof Bed Separation".
[This corrects the article DOI: 10.1021/acsomega.0c03535.].


Expression of merA, amoA and hao in continuously cultured Nitrosomonas europaea cells exposed to zinc chloride additions.
The effects of ZnCl2 additions on a mercuric reductase, merA, ammonia monooxygenase, amoA, and hydroxylamine (NH2OH) oxidoreductase, hao, gene expression were examined in continuously cultured Nitrosomonas europaea cells. The reactor was operated for 85 days with a 6.9 d hydraulic retention time and with four successive additions of ZnCl2 achieving maximum concentrations from 3 to 90 microM Zn2+. Continuously cultured N. europaea cells were more resistant to Zn2+ inhibition than previously examined batch cultured cells due to the presence of Mg2+ in the growth media, suggesting that Zn2+ enters the cell through Mg2+ import channels. The maximum merA up-regulation was 45-fold and expression increased with increases in Zn2+ concentration and decreased as Zn2+ concentrations decreased. Although Zn2+ irreversibly inactivated ammonia oxidation in N. europaea, the addition of either 600 microM CuSO4 or 2250 microM MgSO4 protected N. europaea from ZnCl2 inhibition, indicating a competition between Zn2+ and Cu2+/Mg2+ for uptake and/or AMO active sites. Since ZnCl2 inhibition is irreversible and amoA was up-regulated at 30 and 90 microM additions, it is hypothesized that de novo synthesis of the AMO enzyme is needed to overcome inhibition. The up-regulation of merA during exposure to non-inhibitory Zn2+ levels indicates that merA is an excellent early warning signal for Zn2+ inhibition.


Silica nanoparticle-based dual imaging colloidal hybrids: cancer cell imaging and biodistribution.
In this study, fluorescent dye-conjugated magnetic resonance (MR) imaging agents were investigated in T mode. Gadolinium-conjugated silica nanoparticles were successfully synthesized for both MR imaging and fluorescence diagnostics. Polyamine and polycarboxyl functional groups were modified chemically on the surface of the silica nanoparticles for efficient conjugation of gadolinium ions. The derived gadolinium-conjugated silica nanoparticles were investigated by zeta potential analysis, transmission electron microscopy, inductively coupled plasma mass spectrometry, and energy dispersive x-ray spectroscopy. MR equipment was used to investigate their use as contrast-enhancing agents in T1 mode under a 9.4 T magnetic field. In addition, we tracked the distribution of the gadolinium-conjugated nanoparticles in both lung cancer cells and organs in mice.


Interferon production and natural killer (NK) activity in leukocyte cultures from multiple sclerosis patients.
Peripheral blood leukocyte (PBL) cultures from only 37% of MS patients produced detectable HuIFN-gamma in response to ConA as opposed to 85% of the cultures derived from normal blood donors. However, the yields in patient-derived cultures that were responsive, were not lower than those in cultures from controls. Production of HuIFN-alpha after stimulation with Sendai virus was not aberrant in cells taken from MS patients. The difference in HuIFN-gamma response rate between MS and normal donor-derived cells was more pronounced when DR2+ carriers were compared amongst each other than when DR2-k carriers were compared. Among the MS patients, the failure of PBLs to produce HuIFN-gamma in response to ConA was not correlated with age, sex, disease duration and type of disease. However, positive correlations were found with current disability indices and past disease progression rates. Unstimulated NK-activities of MS patient-derived PBLs were not different from those of normal donor-derived cells. the degree of augmentation of the activity by stimulation with ConA and interferon-alpha was also normal. Within the MS patients group, but not in the control group, there was a trend for DR2+ carriers to have lower spontaneous and stimulated NK-activities than DR2- individuals.


Quantification of liver fat: A comprehensive review.
Fat accumulation in the liver causes metabolic diseases such as obesity, hypertension, diabetes or dyslipidemia by affecting insulin resistance, and increasing the risk of cardiac complications and cardiovascular disease mortality. Fatty liver diseases are often reversible in their early stage; therefore, there is a recognized need to detect their presence and to assess its severity to recognize fat-related functional abnormalities in the liver. This is crucial in evaluating living liver donors prior to transplantation because fat content in the liver can change liver regeneration in the recipient and donor. There are several methods to diagnose fatty liver, measure the amount of fat, and to classify and stage liver diseases (e.g. hepatic steatosis, steatohepatitis, fibrosis and cirrhosis): biopsy (the gold-standard procedure), clinical (medical physics based) and image analysis (semi or fully automated approaches). Liver biopsy has many drawbacks: it is invasive, inappropriate for monitoring (i.e., repeated evaluation), and assessment of steatosis is somewhat subjective. Qualitative biomarkers are mostly insufficient for accurate detection since fat has to be quantified by a varying threshold to measure disease severity. Therefore, a quantitative biomarker is required for detection of steatosis, accurate measurement of severity of diseases, clinical decision-making, prognosis and longitudinal monitoring of therapy. This study presents a comprehensive review of both clinical and automated image analysis based approaches to quantify liver fat and evaluate fatty liver diseases from different medical imaging modalities.


Prostaglandins in cerebrospinal fluid of healthy human volunteers, abstinent alcoholics and rhesus monkeys.
A sensitive and selective assay for measuring prostaglandins in cerebrospinal fluid has been developed, based on the selected-ion-monitoring, electron-capture negative ionization GC/MS detection for the MO-PFB-TMS derivatives of prostaglandins E2, E1, F2 alpha, F1 alpha, and 6-keto-F1 alpha. Improvements over previously published assay procedures have been made, and the new assay has been applied to measurement of prostaglandin concentrations in lumbar CSF of healthy human volunteers, abstinent alcoholic patients, in cisternal CSF of Rhesus monkeys, and continuously sampled lumbar CSF of awake Rhesus monkeys. Results indicated that the concentrations of PGE2, PGE1, PGF1 alpha, and 6-keto-PGF1 alpha were below 15 pg/mL CSF in lumbar CSF of healthy humans and abstinent alcoholics, and in cisternal CSF of Rhesus monkeys. In contrast, continuously sampled lumbar CSF of awake Rhesus monkeys contained more than 200 pg/mL of PGE2, PGF2 alpha, and 6-keto-PGF1 alpha, probably present as a result of local production.


The chemical chaperone sodium 4-phenylbutyrate improves the secretion of the protein CA267T mutant in CHO-K1 cells trough the GRASP55 pathway.
Some inherited coagulation factor deficiencies are caused by intracellular retention or degradation of misfolded proteins, and chemical chaperones have been shown to reverse protein misfolding. The purpose of the present study was to investigate whether chemical chaperones may improve secretion of the protein CA267T (PCA267T) mutant in a cellular model. Using stably transfected Chinese hamster ovary cells (CHO-K1) expressing PCA267T we demonstrate that sodium 4-phenylbutyrate (PBA) increased the secretion of PCA267T by approximately 4-fold in comparison with untreated cells, and that this secretion seemed to follow an unconventional pathway via the Golgi reassembly stacking protein (GRASP55).


KLF2 Regulates Neural Differentiation of Dental Pulp-derived Stem Cells by Modulating Autophagy and Mitophagy.
Transplantation of stem cells for treating neurodegenerative disorders is a promising future therapeutic approach. However, the molecular mechanism underlying the neuronal differentiation of dental pulp-derived stem cells (DPSC) remains inadequately explored. The current study aims to define the regulatory role of KLF2 (Kruppel-like factor 2) during the neural differentiation (ND) of DPSC. We first investigated the transcriptional and translational expression of KLF2, autophagy, and mitophagy-associated markers during the ND of DPSC by using quantitative RT-PCR and western blot methods. After that, we applied the chemical-mediated loss- and gain-of-function approaches using KLF2 inhibitor, GGPP (geranylgeranyl pyrophosphate), and KLF2 activator, GGTI-298 (geranylgeranyl transferase inhibitor-298) to delineate the role of KLF2 during ND of DPSC. The western blot, qRT-PCR, and immunocytochemistry were performed to determine the molecular changes during ND after KLF2 deficiency and KLF2 sufficiency. We also analyzed the oxygen consumption rate (OCR) and the extracellular acidification rate (ECAR) using the Seahorse XFe24 analyzer. Our study demonstrated that the expression level of KLF2, autophagy, and mitophagy-associated markers were significantly elevated during the ND of DPSC. Next, we found that the KLF2 inhibitor, GGPP significantly reduced the ND of DPSC. Inversely, KLF2 overexpression accelerated the molecular phenomenon of DPSC's commitment towards ND, indicating the crucial role of KLF2 in neurogenesis. Moreover, we found that the KLF2 positively regulated autophagy, mitophagy, and the Wnt5a signaling pathway during neurogenesis. Seahorse XFe24 analysis revealed that the ECAR and OCR parameters were significantly increased during ND, and inhibition of KLF2 marginally reversed them towards DPSC's cellular bioenergetics. However, KLF2 overexpression shifted the cellular energy metabolism toward the quiescent stage. Collectively, our findings provide the first evidence that the KLF2 critically regulates the neurogenesis of DPSC by inducing autophagy and mitophagy.


The combi-targetinG concept: intracellular fragmentation of the binary epidermal growth factor (EGFR)/DNA targeting "combi-triazene" SMA41.
We have designed a novel tumor targeting strategy that consists of designing molecules termed "combi-molecules" or TZ-I to be masked forms of multiple antitumor agents. One such molecule SMA41, the TZ-I prototype, has been shown to target the epidermal growth factor receptor (EGFR) and to degrade under physiological conditions to give SMA52 (I) (an inhibitor of EGFR) and methyldiazonium (TZ) (a DNA alkylating species). While the antiproliferative advantages of this novel binary targeting strategy have now been demonstrated, the exact subcellular localization of the degradation products released from SMA41 remained elusive. Here we exploited the fluorescence properties of SMA52 to study its release from SMA41 and its subcellular distribution. Further, using 14C-labeled SMA41, we determined the distribution of the methydiazonium within subcellular macromolecules (DNA, RNA, protein). The results showed that SMA41 degraded to SMA52 in the carcinoma of the vulva cell line A431 with a half-life of 11min. The latter compound was primarily distributed in the perinuclear region. At equimolar concentrations, higher levels of SMA52 were observed when released from SM41 than when the cells were directly exposed to SMA52, indicating that the combi-molecular approach may offer a transport advantage to the released bioactive species. Radioactivity associated with SMA41 3-[ 14C]-methyl group was distributed throughout DNA, RNA, and protein, the latter macromolecule being the most alkylated. The results suggest that SMA41 (TZ-I) may diffuse into the cells, break down into two species: SMA52 (I) concentrated in the perinuclear region and methyldiazonium (TZ) that diffuses in all intracellular organelles and unspecifically alkylates RNA, protein, and nuclear DNA.


Sex differences in methylphenidate-induced dopamine increases in ventral striatum.
Sex differences in the prevalence of dopamine-related neuropsychiatric diseases and in the sensitivity to dopamine-boosting drugs such as stimulants is well recognized. Here we assessed whether there are sex differences in the brain dopamine system in humans that could contribute to these effects. We analyzed data from two independent [11C]raclopride PET brain imaging studies that measured methylphenidate-induced dopamine increases in the striatum using different routes of administration (Cohort A = oral 60 mg; Cohort B = intravenous 0.5 mg/kg; total n = 95; 65 male, 30 female), in blinded placebo-controlled designs. Females when compared to males reported stronger feeling of "drug effects" and showed significantly greater dopamine release in the ventral striatum (where nucleus accumbens is located) to both oral and intravenous methylphenidate. In contrast, there were no significant differences in methylphenidate-induced increases in dorsal striatum for either oral or intravenous administration nor were there differences in levels of methylphenidate in plasma. The greater dopamine increases with methylphenidate in ventral but not dorsal striatum in females compared to males suggests an enhanced sensitivity specific to the dopamine reward system that might underlie sex differences in the vulnerability to substance use disorders and to attention-deficit/hyperactivity disorder (ADHD).


[The EUCORE registry: objectives and general results].
The European Cubicin Outcomes Registry and Experience (EUCORE) is an ongoing, retrospective, European, post-marketing, non-comparative database of daptomycin use in patients that have received at least one daptomycin dose. The primary objective is to evaluate the clinical outcomes of patients treated with this drug. This article presents the analysis of patients included in Spanish institutions from January 2006 to March 2010. A total of 726 patients were included: 66% males, 48.6% aged more than 65 years old, and 70% with comorbidities. Daptomycin was administered in the outpatient setting in 20.3% of the patients. More than 50% of the patients received a dose of 6 mg/kg/day and in 80% daptomycin was administered as a rescue therapy. The median treatment duration was 14 days. The infections treated were bacteremia (32.51%), skin and soft tissue infections (31.4%), infectious endocarditis (14.33%), infections associated with prosthetic materials (10.9%), osteoarticular infections (6.1%), and others. Infections were caused by Staphylococcus aureus (40.5%; 14.4% methicilllin-resistant), coagulase-negative staphylococci (34.5%), enterococci (11.7%) and group viridans streptococci (2.9%). The overall rate of clinical success was 78.4% (81.5% when administered as first-line therapy and 77.6% when administered as rescue therapy). In patients with renal failure, the efficacy of daptomycin was lower. At the end of therapy, 8.7% of patients showed a decrease in creatinine clearance, and in 25 patients creatine kinase values were more than 10 times higher than normal values. Daptomycin is a safe and effective antimicrobial agent for the treatment of severe infections caused by Gram-positive bacteria.


Flow Cytometry-Based Detection of Siglec Ligands.
Siglecs are a family of immunomodulatory cell surface receptors present on white blood cells. Binding to cell surface sialic acid-containing glycans modulates the proximity of Siglecs to other receptors that they regulate. This proximity is key to enabling signaling motifs on the cytosolic domain of Siglecs to modulate immune responses. Given the important roles that Siglecs play in helping to maintain immune homeostasis, a better understanding of their glycan ligands is needed to elucidate their roles in health and disease. A common approach for probing Siglec ligands on cells is to use soluble versions of the recombinant Siglecs in conjunction with flow cytometry. Flow cytometry has many advantages in enabling the relative levels of Siglec ligands between cell types to be rapidly quantified. Here, a step-by-step protocol is described on how to detect Siglec ligands most sensitively and accurately on cells by flow cytometry.


Stimulation of an alpha like DNA polymerase by v-myc related protein of Halobacterium halobium.
Partial DNA sequencing of a genomic clone of the archaebacterium Halobacterium halobium, which hybridized with an avian v-myc probe, showed especially the presence, in the organism of one of the conserved regions through myb, myc and adenovirus E1a oncogenes. The archaebacterial deduced amino acid sequence displayed significant homology with the v-myc gene product. In accordance with the partial DNA sequencing which assured a sufficient homology to have similar epitopes, a protein having a molecular weight of 70,000 and possessing high antigenicity with a polyclonal antiserum against avian v-myc protein was isolated and purified from H. halobium extracts. The purified v-myc like protein stimulated in vitro DNA synthesis carried out by the alpha like DNA polymerase of H. halobium.


Glomerular permeability and polyanion in adriamycin nephrosis in the rat.
Alterations in glomerular permeability were studied in Adriamycin-induced proteinuria in rats by measuring fractional clearances (C/GFR) of uncharged labeled dextrans of varying molecular radii (ae) and of anionic, native, and cationic horseradish peroxidases (HRP) in experimental and control animals. Experimental animals were studied between days 14 and 55 after a single intravenous dose of Adriamycin (doxorubicin), 7.5 mg/kg. Mean proteinuria in the experimental animals was 98 mg/24 hr. Glomerular morphology showed few changes except for epithelial cell swelling, vacuolization, and foot process obliteration, and a significant reduction of glomerular colloidal iron staining. Polyethyleneimine staining revealed a similar distribution of anionic sites in the laminae rarae interna and externa in proteinuric rats as compared with controls. Inulin clearances revealed reduction in GFR and RPF of 20 and 15%, respectively. Dextran C/GFR values showed in experimental animals a size defect for molecules with an ae exceeding 40 A, with a four- to fivefold increase over the values found in control animals for dextrans with ae of 58 and 60 A. The peroxidase clearances showed a slight increase in C/GFR of anionic HRP in experimental animals, as could be expected on the basis of the sieving defect, whereas the C/GFR values for native and cationic HRP were virtually unchanged, indicating an intact functional charge barrier in the proteinuric animals.(ABSTRACT TRUNCATED AT 250 WORDS)


Bacterial contaminants of collected and frozen human milk used in an intensive care nursery.
Use of human milk for preterm and high-risk neonates conveys many potential benefits but also poses practical difficulties. This prospective study examined the prevalence and degree of bacterial contamination of human milk used in the intensive care nursery. One hundred eight milk samples collected from 40 mothers were tested for contamination. Samples from mothers whose milk showed a high degree of contamination were retested after counseling on collection methods. Only 12.5% of the samples showed no bacterial growth. Of the contaminated samples, 38% contained > 30,000 colony-forming units/ml. The most common contaminants were Staphylococcus epidermidis (82%) and Acinetobacter (9%), but other contaminants were also encountered. There were not statistically identifiable common characteristics of mothers whose milk showed abundant bacterial contamination. Only 30% of these mothers showed improvement in the degree of contamination after counseling regarding techniques of milk collection.


Analysis of molecular mobility in corn and quinoa flours through 1H NMR and its relationship with water distribution, glass transition and enthalpy relaxation.
Solids-water interactions of corn and quinoa flours were evaluated through 1H NMR, DSC, and water sorption isotherms. Glass transition temperature (Tg), observed by DSC, was better distinguished through FID signals, and correlated to water content through the Gordon and Taylor model. Enthalpy relaxations, identified by thermal analysis at 50-70 °C were studied through transverse relaxation times (T2) measured after Hahn spin-echo sequence, which revealed a rearrangement of the biopolymers structures that cause immobilization of polymer chains and reduced mobility of water molecules with weak interactions with solids (lower T22). The higher lipid content of quinoa flour was manifested after the CPMG sequence (T2 ≈ 100 ms) and caused reduced hygroscopicity and Tg values compared with corn flour systems. 1H NMR resulted efficient for assigning proton populations and understanding the changes in their distribution with temperature, analyzing glass transition and interpreting the implications of enthalpy relaxations processes in corn and quinoa flours.


Neovascularization and the appearance of morphological characteristics of the blood-brain barrier in the embryonic mouse central nervous system.
Vascularization and expression of blood-brain barrier (bbb)-associated morphological characteristics during the embryonic development of the mouse central nervous system (CNS) was studied by ultrastructural analysis. At embryonic day 9 (E9) capillaries were only found in the perineural mesenchymal tissue. These capillaries showed fenestrations, and pericyte like cells (PC) were found joined to the vessel walls. Around E10 endothelial cells (EC) together with PC started invading the intraneural section. At this stage, the immigrating endothelial cells lost their fenestrations and exhibited numerous, partly extended junctional complexes, which appeared 'tight' in some places. A first intraneural anastomotic plexus was observed at E10, as evidenced by the presence of blood cells in all capillary lumens. While the number of junctional complexes remained constant in intraneural capillaries, the frequency of pinocytotic vesicles decreased significantly from E10 to E17. These findings indicate that from the first day of intraneural vascularization onwards, the morphological properties of the bbb are present in the early embryonic mouse cerebral cortex.


Experiences and needs of older adults at different stages of cerebral infarction based on trajectory theory-A qualitative study.
In recent years, stroke has become the second leading cause of death worldwide, and the incidence and mortality of ischemic stroke have increased significantly. This study mainly aimed to explore the experiences and needs of older adults at different stages of cerebral infarction based on the chronic illness trajectory theory. Data were collected from 22 older adults experiencing the onset, acute, and stable stages of stroke through semi-structured interviews and were analyzed using Colaizzi's descriptive phenomenological approach. Multiple themes and subthemes emerged on the experiences and needs of older adults at different stages of cerebral infarction based on the three dimensions of the long-term disease trajectory theory: illness-related work, biographical work, and everyday life work. Seven themes were extracted for illness-related work, six for biographical work, and eight for everyday life work. The treatment, nursing, and rehabilitation of cerebral infarction are complex. This study indicated that patients after cerebral infarction have different experiences and needs for illness-related work. They also have distinctive and dynamically changing demands for biographical work and everyday life work. The experiences and needs of older patients with cerebral infarction changed dynamically at different stages of the disease. Healthcare professionals should develop effective interventions targeting these needs at various disease stages, provide patients with continuous support to shape their disease trajectories, and maintain patients' stability.


Pitfalls in the reporting of upper endoscopy features in cirrhotic patients.
Upper endoscopy is the main tool for the accurate assessment of the risk of bleeding in cirrhotic patients. To evaluate the diagnostic accuracy of upper endoscopy, in cirrhotic subjects, during common clinical practice. 120 endoscopic reports produced in different hospitals in our region were retrospectively and randomly selected. After a general evaluation, aimed at assessing the description of various endoscopic features, reports were evaluated by four expert endoscopists and four expert hepatologists. Experts were asked to fill in a questionnaire for each single endoscopic procedure, regarding the diagnostic accuracy of the report. Endoscopic reports lacked descriptions of the size of esophageal varices and red signs in 14% and 29% of cases respectively. Presence (or absence) of gastric varices or portal hypertensive gastropathy were not reported in 62% and 34% of cases respectively. According to expert endoscopists 41% of the reports were incomplete, while, according to hepatologists, reports were incomplete and inadequate for clinical purposes in 36% of cases. Our study clearly evidenced a significant lack of information in reports on upper endoscopy in cirrhotic patients, and supports the prompt adoption of corrective strategies.


Oculomotor abnormalities in motor neuron disease.
To determine whether there are oculomotor abnormalities in motor neuron disease (MND), electro-oculographic recordings were performed prospectively in 16 MND patients and the results compared with age-matched healthy controls. Parameters analysed included random and fixed saccades (latency, velocity and accuracy), smooth pursuit (gain, total harmonic distortion and number of saccadic intrusions) and optokinetic nystagmus (maximal and mean slow component velocity). Increased saccadic latencies and decreased smooth pursuit gain were the main alterations in the MND group. Correlation with clinical variables showed a positive relationship between smooth pursuit saccadic intrusions and the bulbar clinical score and the rate of progression and a lower optokinetic nystagmus maximal velocity in patients with pseudobulbar syndrome. Our results demonstrate the presence of subclinical supranuclear abnormalities in MND, and support the notion that MND is not merely a degeneration of the motor system.


Oxidation therapy: the use of a reactive oxygen species-generating enzyme system for tumour treatment.
Oxygen radicals induce cytotoxicity via a variety of mechanisms, including DNA damage, lipid peroxidation and protein oxidation. Here, we explore the use of a polyethylene glycol (PEG)-stabilised enzyme capable of producing reactive oxygen species (ROS), glucose oxidase (GO), for the purpose of harnessing the cytotoxic potential of ROS for treating solid tumours. PEG-GO (200 U), administered by two intratumoral injections 3 h apart, produced a significant growth delay in subcutaneous rat 9L gliomas as compared with control animals receiving heat-denatured PEG-GO. Rats were protected from systemic toxicity by subsequent i.v. administration of PEG-superoxide dismutase (PEG-SOD) and PEG-catalase. In vivo tumour metabolic changes, monitored using 31P magnetic resonance spectroscopy (31P-MRS) 6 h following initial administration of PEG-GO, revealed a 96 +/- 2% reduction in the ATP/Pi ratio and a 0.72 +/- 0.10 unit decline in intracellular pH. A 3-fold sensitisation of 9L glioma cells in vitro to hydrogen peroxide could be achieved by a 24 h preincubation with buthionine sulphoximine (BSO). This study suggests that oxidation therapy, the use of an intratumoral ROS-generating enzyme system for the treatment of solid tumours, is a promising area which warrants further exploration.


Size discrimination among conspecific hostplants in two pierid butterflies; Pieris napi L. and Pontia daplidice L.
Females of the butterflies Pieris napi and Pontia daplidice discriminate against large hostplant individuals, usually preferring low rosettes or seedlings, when hostplants are abundant. In this paper the larval mobility between young hostplant, and differences in survival and growth rate on low versus tall conspecific hostplants were studied in these two species in Sweden. The results suggest that the largest effect of plant size is that small plants support faster growth than bigger ones. This seems to be due to differences in microclimate conditions, not an effect of different suitability as food. Thus, on the assumption that there are no systematic differences in larval death rate, which is supported by the results in this study, preference for small hostplants should be advantagous, leading to higher survival during development, and higher probability for an additional brood per year.


Role of presynaptic and postsynaptic IP3-dependent intracellular calcium release in long-term potentiation in sympathetic ganglion of the rat.
In the rat superior cervical ganglion, a form of long term potentiation (LTP) can be elicited by a brief high frequency stimuli applied to the preganglionic nerve. Cumulative evidence shows that a transient increase in cytoplasmic Ca²+ concentration is essential for the generation of the ganglionic LTP. Calcium influx and calcium release from intracellular calcium stores contribute to LTP. However, the differential role of presynaptic and postsynaptic calcium signaling has not been established. Herein, by using heparin, a membrane-impermeant inositol trisphosphate receptor (IP3R) blocker, we explored the contribution of presynaptic and postsynaptic IP3-sensitive calcium stores to the ganglionic LTP. The LTP was produced by a conditioning train of 40 Hz for 3 s. We analyzed the effects of heparin on the posttetanic potentiation: PTP magnitude and PTP time constant, and on two parameters that describe the LTP: LTP decay time (elapsed time required by the potentiated response to fall to 20% above the basal value) and LTP extent (the integral of the potentiated response). Heparin (100 and 200 μg/ml) was loaded in the preganglionic, the postganglionic, or in both nerves. We found that in all tested conditions heparin significantly decreased LTP but practically did not affect PTP. The preganglionic and postganglionic inhibitory effects of heparin were not additive. De-N-sulfated heparin, an ineffective IP3R blocker, had no effect on LTP, but abolished the heparin blocking effect. Data suggest that presynaptic and postsynaptic IP3-dependent intracellular calcium release equally contribute to ganglionic LTP, supporting our proposal of a trans-synaptic mechanism for LTP.


"Trans-zygomatic approach" for reduction & internal fixation of a malunited, medially dislocated condyle fracture in a geriatric patient with cervical spine injury.
The open reduction and internal fixation of medially displaced/dislocated condyle fracture is challenging due to inadequate visibility and access to the dislocated condyle. The common approach to reduction of such condyles is by inferior distraction of the mandible which facilitates visualization as well as instrumentation. However, this maneuver may be difficult, or contraindicated in patients with concomitant cervical spine injury where excessive manipulation of the mandible may predispose the spine to further trauma. Ramus osteotomies which are used when conventional reduction methods fail, facilitate reduction but are associated with additional incision, complications and surgical time. This case report presents an alternative method, the "trans-zygomatic approach" which was used effectively to reduce a dislocated and malunited condyle fracture in a geriatric patient with co-existent cervical spine injury. The approach facilitated precise reduction of condyle fracture with minimal impact on the cervical spine.


Structure of a triphosphonopentaosylceramide containing 4-O-methyl-N-acetylglucosamine from the skin of the sea hare, Aplysia kurodai.
A novel phosphonoglycosphingolipid named SGL-I containing 3 mol of 2-aminoethylphosphonate residues was isolated from the skin of a sea gastropod, Aplysia kurodai. The saccharide moiety of the glycolipid was characterized as 4-O-methyl-GlcNAc alpha 1----4GalNAc alpha-1----3 [6'-O-(2-aminoethylphosphonyl)Gal alpha 1----2] (2-aminoethylphosphonyl----6)Gal beta 1----4(2-aminoethylphosphonyl----6) Glc beta 1----1-ceramide. The major aliphatic components of the ceramide portion were palmitic acid, stearic acid, octadeca-4-sphingenine, and anteisononadeca-4-sphingenine. This glycolipid is unique in containing 4-O-methyl-N-acetylglucosamine and 3 mol of 2-aminoethylphosphonate residues, one of which is attached to C-6 of glucose.


Efficacy of phenytoin against hyponatremic seizures due to SIADH after administration of anticancer drugs in a neonate.
A neonate with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) developed refractory hyponatremic seizures following administration of anticancer drugs. The seizures did not respond to diazepam, phenobarbital, or lidocaine, but resolved immediately with administration of phenytoin. The low water-excretion capacity in neonates should be taken into consideration when fluid loading is attempted, to avoid renal damage upon administration of drugs such as cisplatin that have a potential damaging effect on the kidney. Phenytoin could be the therapy of choice for SIADH and resulting seizures in the neonatal period.


Evaluation of two commercially available DNA tests for detection of human papillomavirus.
This study was designed to compare the sensitivity, specificity, efficiency, positive and negative predictive values, and ease of use for 2 commercially available hybridization kits for detecting human papillomavirus (HPV) DNA: Oncor Southern blot (SB) (Oncor, Inc., Gaithersburg, MD) and Digene ViraType dot blot (DB) (Digene Diagnostics, Inc., Silver Spring, MD). A total of 179 specimens (172 cervical and 7 penile biopsies) were assessed for acceptability based on the presence of epithelial cells and tested for HPV by DB and SB. The results were evaluated based on Papanicolaou-stained cervical specimens and selected risk factors. One hundred six (97.2%) of 109 results were concordant, i.e., 93 negative (85.3%) and 13 positive (11.9%). Using SB as the gold standard, we found the sensitivity, specificity, efficiency, and positive and negative predictive values for the ViraType DB to be 100%, 96.9%, 97.3%, 81.3%, and 100%, respectively. Comparing the Papanicolaou smear to SB and DB, we found the sensitivity, specificity, efficiency, and positive and negative predictive values to be 33.3% (SB) vs. 44.4% (DB), 89.5% vs. 87.6%, 87.3% vs. 84.2%, 11.8% vs. 23.5%, and 97.0% vs. 94.9%, respectively. The only significant risk factor for predicting an HPV infection was the number of sexual partners. Although SB has been considered the standard model, DB is an acceptable method for detecting and identifying HPV infections.


Do postpartum nonsteroidal antiinflammatory drugs (NSAIDs) affect neonatal hyperbilirubinaemia?
There has been no previous study on the interaction between neonatal hyperbilirubinemia and NSAID use in breastfeeding mothers. This study aimed to investigate whether postpartum analgesics (with NSAIDs) can affect neonatal hyperbilirubinaemia. Mothers who gave birth between January 2017 and December 2017 were included. Those who were not exclusively breastfeeding, gave premature birth, who underwent caesarean section, or whose infants had abnormalities such as an imperforated anus, diaphragmatic hernia, or ovarian tumour were excluded. Mothers were divided into 2 groups based on the analgesics received postpartum: acetaminophen and NSAID (non-steroidal anti-inflammatory drug; flurbiprofen) users. Multivariable logistic regression was adopted to estimate the risk of hyperbilirubinaemia with the use of different kinds of painkillers. In total, 1153 mothers were reviewed. After applying the exclusion criteria, 480 mothers were finally included in the analyses. Among them, 348 (72.67%) and 132 (27.33%) mothers received acetaminophen and flurbiprofen, respectively. Seven (2.01%) and 1 (0.76%) newborn had hyperbilirubinaemia among the acetaminophen and flurbiprofen users, respectively. Hyperbilirubinaemia risk of infants whose mothers were flurbiprofen users was not significantly different from that of infants whose mothers were acetaminophen users (adjusted odd ratio = 0.50, 95% confidence interval = 0.06-4.50, p-value = 0.4552). Breastfeeding mothers receiving flurbiprofen do not have increased risk of neonatal hyperbilirubinaemia.


Diagnostic accuracy of a new ex vivo confocal laser scanning microscope compared to H&E-stained paraffin slides for micrographic surgery of basal cell carcinoma.
For safe excision of malignant skin tumours, complete negative surgical margins are mandatory. The gold standard for analysis is frozen sections or paraffin-embedded haematoxylin and eosin (H&E)-stained slides. The production of H&E-stained slides is time-consuming (>20 h) while wounds remain unclosed. An upcoming method is confocal laser scanning microscopy (CLSM), a technique that scans unfixed fresh tissue rapidly. Evaluation of the process to generate and analyse CLSM images and assessment of the accuracy to detect basal cell carcinoma (BCC) tissue. Digital microscopic images were generated by the Histolog Scanner v1 from 544 fresh specimens of 148 BCCs that had been stained with a 0.01% proflavine solution. CLSM images were compared to the histological diagnoses of the corresponding H&E-stained slides. A total of 525 images could be analysed. The sensitivity was 73% (95% CI = [65.27%; 80.47%]), and the specificity was 96% (95% CI = [93.40%; 97.60%]). Detection of BCCs in punch biopsies was certainly detected (sensitivity of 100%). The median total time to generate and evaluate a CLSM image was 5.17 min (maximum 20.17 min and minimum 2.05 min). The greatest challenge was flattening the specimen to assure complete representation of the surgical margins. Confocal laser scanning microscopy is a time-saving and very effective alternative to classical paraffin-embedded or frozen sections. Patient treatment could be improved due to shorter hospital stays or faster outpatient therapy due to reduced intervals between surgical stages. Diagnostic accuracy of the microscope used still must be improved.


Immune deficiency, thrombocytopenia and osteomyelitis in pediatric patients.
Surgical decompression of osteomyelitis in pediatric patients should be an essential part of therapy in most cases. The initial deferral of prompt decompression in two patients because of underlying chronic, hemorrhagic (thrombocytopenic) disorders-one with Wiskott-Aldrich syndrome and one with Gaucher's disease-resulted in more serious and prolonged courses of the infectious processes. The complications might have been ameliorated by earlier drainage in each case. Based upon the experience gained from these two patients, we recommend early drainage, with appropriate treatment of the hemorrhagic disorder, to prevent more widespread dissemination or prolongation of osseous infection in similarly affected children.


Assessing the electrochemical degradation of reactive orange 84 with Ti/IrO2-SnO2-Sb2O5 anode using electrochemical oxidation, electro-Fenton, and photoelectro-Fenton under UVA irradiation.
Today, water shortage problems around the world have forced the search for new treatment alternatives, in this context, electrochemical oxidation technology is a hopeful process for wastewater treatment, although it is still needed exploration of new efficient and economically viable electrode materials. In this way, mixed metal oxide anodes look like promising alternatives but their preparation is still a significant point to study, searching for finding low-cost materials to improve electrocatalytic efficiencies. In an exploration of this kind of highly efficient materials, this work presents the results obtained using an MMO Ti/IrO2-SnO2-Sb2O5 anode. All the prepared anodes exhibited excellent physical and electrochemical properties. The electrochemical oxidation of 100 mL and 200 mg L-1 Reactive Orange 84 (RO 84) diazo dye was studied using 3 cm2 of such synthesized anodes by applying current densities of 25, 50, and 100 mA cm-2. Faster and more efficient electrochemical oxidation occurred at 100 mA cm-2 with 50 mM of Na2SO4 + 10 mM NaCl as supporting electrolyte at pH 3.0. The degradation and mineralization processes of the above solution were enhanced with the electro-Fenton process with 0.05 mM Fe2+ and upgraded using photoelectron-Fenton with UVA light. This process yielded 91% COD decay with a low energy consumption of 0.1137 kWh (g COD)-1 at 60 min. The evolution of a final carboxylic acid like oxalic was followed by HPLC analysis. The Ti/IrO2-SnO2-Sb2O5 is then an efficient and low-cost anode for the photoelectro-Fenton treatment of RO 84 in a chloride and sulfate media.


Classification of Speaking and Singing Voices Using Bioimpedance Measurements and Deep Learning.
The acts of speaking and singing are different phenomena displaying distinct characteristics. The classification and distinction of these voice acts is vastly approached utilizing voice audio recordings and microphones. The use of audio recordings, however, can become challenging and computationally expensive due to the complexity of the voice signal. The research presented in this paper seeks to address this issue by implementing a deep learning classifier of speaking and singing voices based on bioimpedance measurement in replacement of audio recordings. In addition, the proposed research aims to develop a real-time voice act classification for the integration with voice-to-MIDI conversion. For such purposes, a system was designed, implemented, and tested using electroglottographic signals, Mel Frequency Cepstral Coefficients, and a deep neural network. The lack of datasets for the training of the model was tackled by creating a dedicated dataset 7200 bioimpedance measurement of both singing and speaking. The use of bioimpedance measurements allows to deliver high classification accuracy whilst keeping low computational needs for both preprocessing and classification. These characteristics, in turn, allows a fast deployment of the system for near-real-time applications. After the training, the system was broadly tested achieving a testing accuracy of 92% to 94%.


Cytosporacin, a highly unsaturated polyketide: application of the ACCORD-ADEQUATE experiment to the structural determination of natural products.
Cytosporacin (1), a novel antibacterial polyketide containing naphthopyranone and isochromandione moieties, was isolated from the fermentation broth of the fungus Cytospora rhizophorae. A (1)H-detected ACCORD-ADEQUATE pulse sequence that distinguished (2)J(CH) from (3)J(CH) correlations provided critical information for structural determination. NOE studies established the relative configuration and revealed the presence of two rotamers. A biosynthetic (13)C-labeling experiment indicated that cytosporacin was derived from acetate origin.


Usefulness of contrast-enhanced ultrasonography for intracystic breast tumors: a report of three cases.
Cystic breast lesions are caused by a wide spectrum of breast diseases and can range from simple cysts to malignant tumors. Ultrasonography is a good tool for evaluation of the morphology and vascularity of cystic breast lesions. We report three patients in whom contrast-enhanced ultrasonography (CEUS) was used to evaluate intracystic tumors. One of the three patients was diagnosed with intracystic papilloma. Compared with conventional ultrasonography alone, CEUS more clearly demonstrated that the solid component within the mass was lobulated with a narrow base. The other two patients were diagnosed with intracystic papillary carcinoma, and CEUS clearly revealed the presence of widely elevated solid components within both masses, suggesting malignancy. Therefore, CEUS simplified morphological evaluation by enhancing the solid components within the cystic masses.


The association between eye color and corneal sensitivity measured using a Belmonte esthesiometer.
The purpose of this study is to determine the association between corneal sensitivity measured using a pneumatic esthesiometer and eye color quantified objectively. Twenty subjects had ocular surface sensitivity measured using a Belmonte esthesiometer. An ascending method of limits followed by the method of constant stimuli were used to estimate 1) cold detection thresholds, 2) discomfort detection thresholds (both using pneumatic stimuli at 20 degrees C, 3) mechanical detection thresholds using pneumatic stimuli at 50 degrees C (ocular surface temperature approximately 33 degrees C), and 4) percent CO2 chemical detection thresholds using 50 degrees C pneumatic stimuli at flow rates set at half of each subject's pneumatic detection threshold (therefore detected by the chemical content and not the mechanical content). Eye color was estimated 1) clinically by two observers ranking the color (light to dark) of digital images of each subject's iris, 2) photometrically by measuring iris luminance, and 3) using chromaticity obtained from a Photo Research 650 spectroradiometer with controlled illumination. Correlation and linear and nonlinear regression analyses were used to examine relationships between variables. There were no associations between eye color (determined clinically or objectively) for mechanical and chemical detection thresholds (best r = 0.15, all p > 0.05). There was a significant linear association between 20 degrees detection thresholds and eye color (r = 0.39), which was substantially improved with a two-line function (part level and part increasing linearly, r = 0.65). We were generally unable to demonstrate the relationship between eye color and sensitivity reported previously using a Cochet-Bonnet esthesiometer. However, for a subset of subjects with palest irises, there appears to be a linear association between eye color and sensitivity to cooling stimuli.


Small RNA transcriptome analysis using parallel single-cell small RNA sequencing.
miRNA and other forms of small RNAs are known to regulate many biological processes. Single-cell small RNA sequencing can be used to profile small RNAs of individual cells; however, limitations of efficiency and scale prevent its widespread application. Here, we developed parallel single-cell small RNA sequencing (PSCSR-seq), which can overcome the limitations of existing methods and enable high-throughput small RNA expression profiling of individual cells. Analysis of PSCSR-seq data indicated that diverse cell types could be identified based on patterns of miRNA expression, and showed that miRNA content in nuclei is informative (for example, cell type marker miRNAs can be detected in isolated nuclei). PSCSR-seq is very sensitive: analysis of only 732 peripheral blood mononuclear cells (PBMCs) detected 774 miRNAs, whereas bulk small RNA analysis would require input RNA from approximately 106 cells to detect as many miRNAs. We identified 42 miRNAs as markers for PBMC subpopulations. Moreover, we analyzed the miRNA profiles of 9,533 cells from lung cancer biopsies, and by dissecting cell subpopulations, we identified potentially diagnostic and therapeutic miRNAs for lung cancers. Our study demonstrates that PSCSR-seq is highly sensitive and reproducible, thus making it an advanced tool for miRNA analysis in cancer and life science research.