A pancreatic-type phospholipase A2 in rat gastric mucosa.
A phospholipase A2, which is immuno-crossreactive with the anti-rat pancreatic phospholipase A2 antibody, is present in rat gastric mucosa. The content of the enzyme in the gastric mucosa was comparable to that in the pancreas, but the specific activity in the gastric mucosa homogenate (60.7 +/- 19.5 nmol/min/mg) was higher than that in the pancreas homogenate (3.16 +/- 0.77 nmol/min/mg). A greater proportion of the enzyme was found in the particulate fraction. The gastric enzyme and its proenzyme were purified from the supernatant. The amino acid sequence of the N-terminal 15 residues of the gastric enzyme was determined and found to be identical with that of rat pancreatic phospholipase A2. Like the pancreatic proenzyme, the gastric proenzyme was activated on trypsin treatment.


Lens epithelium supports axonal regeneration of retinal ganglion cells in a coculture model in vitro.
The purpose of this study was to determine whether the lens epithelium influences the survival or axonal growth of regenerating retinal ganglion cells. The optic nerves of adult albino rats were injured in order to induce axonal regeneration, and axon growth was then studied in retinal explants in the presence of cocultivated lens capsules carrying living epithelial cells. In the first series of experiments, cocultivation of retinal explants with lens epithelium in immediate proximity resulted in penetration of fibers into the lens epithelium, indicating that it supported axonal growth. In the second series of experiments, co-explants were placed 0.5-1.0mm from each other. The numbers of outgrowing retinal axons were determined both with respect to the retinal eccentricity and the topological relationship with the lenticular co-explant. The Wilcoxon matched-pairs signed-rank test was used to determine if the numbers of axons differed significantly between four regions of the explants. Significantly more axons grew out from the retinal edge facing the lenticular explant than from its opposite side, indicating that the lens epithelium supports axon growth. The numbers of surviving retinal ganglion cells in culture were determined after retrograde prelabelling with a neuroanatomical tracer. The number of fluorescent ganglion cells within the retinal explants did not significantly differ between the groups (Mann-Whitney test). These findings indicate that the lens epithelium influences both the amount of axonal regeneration and the direction of growth without affecting the survival rate of retinal ganglion cells in vitro.


Vibration-induced injuries in workers exposed to transient and high frequency vibrations.
The risk of developing vibration white fingers and neurosensory symptoms increases with the duration and intensity of the exposure. The aim of this study was to investigate the risk of developing vibration white fingers (VWF), neurosensory symptoms and musculoskeletal disorders among workers exposed to transient and high frequency vibrations. The study included 38 vibration exposed workers from a loader assembly plant in Sweden (30 males and 8 females). All participants answered questionnaires and had a structured interview about work and medical history. A following medical examination included the determination of vibration and temperature perception thresholds and musculoskeletal symptoms in the neck, shoulder, elbow and hands. The individual vibration exposure expressed as A (8)-values and vibration exposure in minutes per day, were obtained from questionnaires answered by the participants. The prevalence of VWF was 30% among the male workers and 50% among the females. The corresponding prevalence of neurosensory symptoms was 70% among the males and 88% among the females. Musculoskeletal findings were common among the male workers. Dominant symptoms/syndromes were tension neck syndrome, biceps tendinitis, carpal tunnel syndrome and ulnar entrapment in hand/wrist. A total of 32 diagnoses were observed among the male workers and four diagnoses among the female workers. Numbness in fingers and age had the strongest impact on perceived work ability. ISO 5349-1 considerably underestimates the risks of VWF for this group of workers exposed to transient and high frequency vibrations. It is therefore important to develop a risk assessment standard also covering this frequency range.


Retooling the ethanol industry: thermophilic anaerobic digestion of thin stillage for methane production and pollution prevention.
Anaerobic digestion of corn ethanol thin stillage was tested at thermophilic temperature (55 degrees C) with two completely stirred tank reactors. The thin stillage wastestream was organically concentrated with 100 g/L total chemical oxygen demand and 60 g/L volatiles solids and a low pH of approximately 4.0. Steady-state was achieved at 30-, 20-, and 15-day hydraulic retention times (HRTs) and digester failure at a 12-day HRT. Significant reduction of volatile solids was achieved, with a maximum reduction (89.8%) at the 20-day HRT. Methane yield ranged from 0.6 to 0.7 L methane/g volatile solids removed during steady-state operation. Effluent volatile fatty acids below 200 mg/L as acetic acid were achieved at 20- and 30-day HRTs. Ultrasonic pretreatment was used for one digester, although no significant improvement was observed. Ethanol plant natural gas consumption could be reduced 43 to 59% with the methane produced, while saving an estimated $7 to $17 million ($10 million likely) for a facility producing 360 million L ethanol/y.


Online seminars as an information source for direct-to-consumer stem cell therapy.
Aim: To attend stem cell (SC) seminars hosted by US-based direct-to-consumer SC businesses either in person or via online 'webinars' to determine accuracy and regulatory oversight of the advertised SC therapies. Methods: The therapeutic claims, costs, risks, scientific evidence in support of a therapy and any regulatory oversight were collated using pre-established checklists. Participation consisted of one live attendance of a seminar, and following COVID-19 restrictions, review of seven recorded presentations available on the internet from SC businesses. Results & conclusion: None of the SC therapies advertised by direct-to-consumer clinics reviewed were supported by proper clinical evidence nor substantiated by peer reviewed literature.


Prevalence of usage of Tobacco and its various correlates in District Gautam-Budh Nagar, Uttar Pradesh.
Tobacco use is the leading single preventable cause of deaths worldwide. India is the second largest consumer of tobacco in the world. To study the prevalence of tobacco use among the adult population >15 years age of District Gautam-Budh Nagar and find the association of various socio-demographic factors with the tobacco usage. Cross-sectional community-based study conducted in urban and rural areas of District Gautam-Budh Nagar, Uttar-Pradesh. The study was conducted among 1461 adults aged 15 years and above in the District Gautam-Budh Nagar. Multistage sampling was used to select the study subjects. The questionnaire used for the interview consisted of questions related to socio-demographic profile, smoking habits and smokeless tobacco use, intention to quit and exposure to second-hand smoke. The data were entered and analyzed in SPSS Software version 20.0. The prevalence of tobacco use was expressed in percentages. The association between various socio-demographic factors and tobacco use was assessed by Chi-square test. P value < 0.05 was taken as significant. Prevalence of tobacco usage in this study was found to be 50.4% (65% among males and 28.8% among females). The prevalence of smoking and smokeless tobacco use in our study was 37.2% and 21.3%, respectively. Increasing age, male gender, and lower educational status were found to be significant risk factors for tobacco use in our study. India needs to gear up the efforts more and can still do more to make the proven tobacco control tools work for its citizens' well-being.


Testicular prostheses in children: Is earlier better?
The absence of a testis occurs for various reasons in children, but testicular prosthesis implantation in children is uncommon. The optimal time for prosthesis placement is still unclear, and its complication rate has been poorly studied in children. The aim of this study was to determine the risk factors of complications in cases of testicular prosthesis implantation in children. A monocentric, retrospective review was performed of children implanted with a testicular prosthesis between 2008 and 2014. All implantations were performed through an inguinal incision with a standardized procedure. Children were divided into two groups depending on the interval after orchiectomy: (A) early implantation (delay between surgeries <1 year); and (B) delayed surgeries (delay ≥1 year). Statistical analysis was performed with Student and Fisher tests. Twenty-six patients (A, 15; B, 11) had a total of 38 testicular prostheses placements. Mean follow-up was 36.2 months. First surgery was performed at the mean age of 11.8 years (range 0-17.9) (A, 14.1; B, 8.1; P = 0.01) and testicular prosthesis implantation at the mean age of 14.7 years (range 9-18) (A, 14.3; B, 14.6) with a mean delay of 36.1 months (A, 1.3; B, 80.3). Indications were mainly spermatic cord torsion (27%), bilateral anorchia (27%), and testicular atrophy after cryptorchidism surgery (19.2%). Complications (10.5%) included two cases of extrusion, one infection and one migration. Patient 1 had a history of acute lymphoblastic leukemia with testicle relapse 2 years after induction therapy. High-dose chemotherapy, total body irradiation and bilateral orchiectomies were performed, and bilateral prostheses were implanted 12 years after the end of chemotherapy. Complications happened 85 days after surgery. Patient 2 was followed-up for a proximal hypospadias. The tunica vaginalis flap, which was used during a redo urethroplasty, lead to testicular atrophy. Thirteen years after the last penile surgery, a testicular prosthesis was placed through an inguinal incision, and extrusion occurred 203 days after surgery. Bacterial cultures of the prostheses were sterile and histological review showed no sign of granuloma or graft rejection. The complication rate was significantly higher if the delay between the two surgeries exceeded 1 year (P = 0.01). Indications of orchiectomy, prior scrotal incision, and prosthesis size were not risk factors. Testicular prosthesis implantation was relatively safe in a pediatric cohort. The complication rate was significantly higher if the delay between the orchiectomy and the prosthetic placement exceeded 1 year. These results suggest that reducing the delay between orchiectomy and prosthesis implantation may lead to fewer complications.


[Study in safety of total thyroidectomy].
To study the complications in total thyroidectomies and the safety of total thyroidectomy. Retrospective analyses 351 cases underwent total thyroidectomy in our department. Preoperative and postoperative electronic laryngoscopy were used to assess the vocal cord function. All patients have serum calcium analysis on the operative day and 3rd and 7th day after operation. Temporary hypocalcaemia occurred in 47.01% after total thyroidectomy, but only 15.67% with severe symptom temporarily,and 21.37% with temporary mild numbness. Permanent hypoparathyroidism occurred in 0.85% patients. None with bilateral recurrent laryngeal nerve palsy, and temporary unilateral vocal cord palsy occurred in 1.42% patients and permanent unilateral recurrent laryngeal nerve palsy occurred in 0.56% patients. Total thyroidectomy is safe with low complications.


Detection of a streptomycin/spectinomycin adenylyltransferase gene (aadA) in Enterococcus faecalis.
Genes encoding streptomycin/spectinomycin adenylyltransferases [ANT(3")(9)] have been reported to exist in gram-negative organisms and Staphylococcus aureus. During a study of high-level aminoglycoside resistance in enterococci, we encountered an isolate of Enterococcus faecalis that was streptomycin resistant but did not appear to contain the 6'-adenylyltransferase gene (aadE) when examined by PCR with specific primers. Phosphocellulose paper binding assays indicated the presence of an ANT(3")(9) enzyme. Streptomycin and spectinomycin MICs of 4,000 and 8,000 microg/ml, respectively, were observed for the isolate. PCR primers corresponding to a highly conserved region of the aadA gene were used to amplify a specific 284-bp product. The product hybridized with a digoxigenin-labeled PCR product from E. coli C600(pHP45Omega) known to contain the aadA gene. The aadA gene was transferred via filter matings from the E. faecalis donor to E. faecalis JH2-2. PCR primers designed for analysis of integrons were used to amplify a 1-kb product containing the aadA gene, which was cloned into the vector pCRII and transformed into Escherichia coli DH5-alpha competent cells. D-Rhodamine dye terminator cycle sequencing was used to determine the gene sequence, which was compared to previously reported sequences of aadA genes. We found the aadA gene in E. faecalis to be identical to the aadA genes reported by Sundstr om et al. for E. coli plasmid R6-5 (L. Sundström, P. Râdström, G. Swedberg, and O. Sköld, Mol. Gen. Genet. 213:191-201, 1988), by Fling et al. for the aadA within transposon Tn7 (M. E. Fling, J. Kopf, and C. Richards, Nucleic Acids Res. 13:7095-7106, 1985), and by Hollingshead and Vapnek for E. coli R538-1 (S. Hollingshead and D. Vapnek, Plasmid 13:17-30, 1985). Previous reports of the presence of the aadA gene in enterococci appear to be erroneous and probably describe an aadE gene, since the isolates were reported to be susceptible to spectinomycin.


Cell-Free Circulating (Tumor) DNA before Surgery as a Prognostic Factor in Non-Metastatic Colorectal Cancer: A Systematic Review.
Identification of non-metastatic colorectal cancer (CRC) patients with a high risk of recurrence after tumor resection is important to select patients who might benefit from adjuvant treatment. Cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) analyses after surgery are promising biomarkers to predict recurrence in these patients. However, these analyses face several challenges and do not allow guidance of neoadjuvant treatment, which might become a novel standard option in colon cancer treatment. The prognostic value of cfDNA/ctDNA before surgery is unclear. This systematic review aims to provide an overview of publications in which the prognostic value of presurgery cfDNA/ctDNA in non-metastatic CRC patients was studied and is performed according to PRISMA guidelines. A total of 29 out of 1233 articles were included and categorized into three groups that reflect the type of approach: measurement of cfDNA, ctDNA somatic alterations, and ctDNA methylation. Overall, a clear association between presurgery cfDNA/ctDNA and the outcome was not observed, but large studies that primarily focus on the prognostic value of presurgery cfDNA/ctDNA are lacking. Designing and performing studies that focus on the value of presurgery cfDNA/ctDNA is needed, in addition to standardization in the reporting of cfDNA/ctDNA results according to existing guidelines to improve comparability and interpretation among studies.


CFTR may play a role in regulated secretion by lymphocytes: a new hypothesis for the pathophysiology of cystic fibrosis.
Human lymphocytes and pancreatic acinar cells have a common function: both cell types secrete specific proteins in response to extracellular signals. Acinar cells secrete digestive enzymes, while lymphocytes secrete antibodies and cytokines. Both cell types utilize similar receptor-mediated activation systems, similar signal transduction pathways (i.e., alpha adrenergic receptors, and cAMP), and express the cystic fibrosis transmembrane conductance regulator (CFTR). Preliminary tests of the hypothesis that B lymphocytes are capable of regulated secretion were carried out using transformed lymphocytes. lambda light chain secretion rates were measured in response to treatment with 8-CPT-cAMP. A rapid transient increase in secretion was observed in non-CF lymphocytes. This effect was absent in CF lymphocytes. A failure of regulated secretion could cause a reduced response to antigen presentation, and an inability to completely clear pathogens such as Pseudomonas aeruginosa. Another piece of circumstantial evidence is that lung-transplanted CF patients remain chronically ill. While immunosuppressive therapy may contribute to the chronic illness, the phenomenon is more acute in CF lung-transplant patients than non-CF lung-transplant recipients receiving the same immunosuppressive therapy. A defect in regulated secretion of antibodies and cytokines in response to antigens may be the source of a long suspected, but as yet unproved CFTR-mediated immunological defect underlying the pulmonary morbidity and mortality in cystic fibrosis (CF).


Benefit and advantage to clinicians of a computer-assisted microbiological diagnosis and database system.
Computer-assisted diagnostic systems may accelerate transmission of microbiological reports and facilitate evaluation of the epidemiological situation and thus improve the collaboration between microbiologists and clinicians. This possible benefit is demonstrated by four examples. It became evident that incidences of pathogens in urinary tract and respiratory tract infections varied within a great range, depending on patient groups and clinical departments involved. Even within a department, different incidences of penicillin G and oxacillin-resistant coagulase-negative staphylococci were demonstrated. An apparent homogeneity of distribution of pathogenic bacteria in a hospital tends to be the result of a nondiscriminating overall evaluation, thus necessarily misleading the clinician especially in empirical chemotherapy. In the last example the evaluation of susceptibility testing revealed changing patterns of some pathogens during the observation period. By rapid exchange of data between the laboratories and the clinical departments supplying the clinicians with information relevant for actual therapeutical decisions, an empiric therapy may change into a so-called calculated therapy based upon data directly related to the site of infection, department and susceptibility patterns.


Ogston's coccus.
One hundred and thirty years ago, Alexander Ogston, a surgeon in Aberdeen, first saw micro-organisms in pus from an abscess, which he later called 'staphylococci'. He had already introduced 'Listerism' to Aberdeen, but wished to know more about the cause of infections. He extended Koch's work on 'traumatic wound infection in animals' to humans by a series of ingenious experiments. He used the most modern German microscopes and Koch's stains to study pus from abscesses, and was first to grow staphylococci in artificial cultures (hens' eggs). From 1878 to 1883 the laboratory in his garden was a major UK bacteriology research laboratory. Eventually he became Regius Professor of Surgery and had to 'leave research to others'.


Temperature, age, and recurrence of febrile seizure.
Prediction of a recurrent febrile seizure during subsequent episodes of fever. Study of the data of the temperatures, seizure recurrences, and baseline patient characteristics that were collected at a randomized placebo controlled trial of ibuprofen syrup to prevent febrile seizure recurrences. Two pediatric hospitals in the Netherlands. A total of 230 children with an increased risk of febrile seizure recurrence. Seizure recurrence during a subsequent fever episode. A total of 509 episodes of fever were registered with 67 recurrences; 35 (52%) recurrences within the first 2 hours after fever of onset had a lower median temperature (39.3 degrees C) than 32 (48%) after more than 2 hours of fever (40.0 degrees C, P<.001). Poisson regression analysis resulted in 3 univariably significant (P<.05) predictors of a recurrence of seizure during a subsequent episode of fever. In a multivariable model, they were corrected for their correlation: interval between the last previous seizure and fever of onset less than 6 months (relative risk= 1.3 [95% confidence interval: 0.8-2.4]), age at fever of onset (relative risk=0.7 [95% confidence interval: 0.5-1.0] per year increase) and temperature at fever of onset (relative risk = 1.7 [95% confidence interval: 1.1-2.8] per degree Celsius increase). Half of the recurrent seizures occur in the first 2 hours after fever of onset of a subsequent fever episode. If seizure recurs at a later time, the temperature at seizure is higher compared with recurrences occurring in the first 2 hours of fever. Young age at fever of onset, high temperature at fever of onset, and high temperature during the episode of fever are associated with an increased risk of a recurrent febrile seizure at the moment that a child with a history of febrile seizures has fever again.


Prevalence and Prognostic Significance of Runs of Premature Atrial Complexes in Ischemic Stroke Patients.
Runs of premature atrial complexes (PACs) are common in stroke patients and perceived to be clinically insignificant, but their prognostic significance is unclear. This study investigated the association between runs of PACs in ischemic stroke patients and the risk of recurrent ischemic strokes/transient ischemic attacks (TIAs) or death. The study included consecutive patients admitted with an ischemic stroke from August 2008 to April 2011. Patients with known and newly detected atrial fibrillation were excluded. Runs of PACs were defined as 3 or more PACs lasting less than 30 seconds during 48 hours of continuous inpatient cardiac telemetry. The patients were followed for 4 years or until death, whichever came first. They were stratified according to stroke severity. The combined primary endpoint was a recurrent ischemic stroke/TIA or death. Of the 565 patients included in the study, 28% had runs of PACs. Patients with runs of PACs were likely to be older, female, and to have experienced more severe strokes. During the follow-up, 210 (37%) patients had a recurrent ischemic stroke/TIA (n = 73) or died (n = 137) respectively. Among the 489 patients who had mild-to-moderate strokes, runs of PACs were associated with recurrent ischemic strokes/TIAs or death (hazard ratio = 1.47; 95% CI 1.06-2.04; P = .023). Runs of PACs were frequent in patients with acute ischemic strokes and sinus rhythm, and they were independently associated with an increased risk of recurrent ischemic strokes/TIAs or death in patients with mild-to-moderate strokes.


Recent advances in smooth muscle tumors with PGR and PLAG1 gene fusions and myofibroblastic uterine neoplasms.
Uterine epithelioid and myxoid leiomyosarcomas and inflammatory myofibroblastic tumors are rare mesenchymal neoplasms. Next-generation sequencing recently detected novel PGR fusions in uterine epithelioid leiomyosarcomas that demonstrate characteristic rhabdoid and spindled morphology. PLAG1 gene fusions have also been identified in a subset of myxoid leiomyosarcomas and are associated with PLAG1 overexpression. ALK rearrangements underpin the vast majority of uterine inflammatory myofibroblastic tumors, which demonstrate morphologic, and immunohistochemical features similar to those of inflammatory myofibroblastic tumors elsewhere. This review summarizes the morphologic, immunophenotypic, and molecular genetic features of PGR fusion-positive epithelioid leiomyosarcoma, PLAG1 fusion-positive myxoid leiomyosarcoma, and inflammatory myofibroblastic tumors of the uterus.


Haplotype-Resolved, Chromosome-Level Assembly of White Clover (Trifolium repens L., Fabaceae).
White clover (Trifolium repens L.; Fabaceae) is an important forage and cover crop in agricultural pastures around the world and is increasingly used in evolutionary ecology and genetics to understand the genetic basis of adaptation. Historically, improvements in white clover breeding practices and assessments of genetic variation in nature have been hampered by a lack of high-quality genomic resources for this species, owing in part to its high heterozygosity and allotetraploid hybrid origin. Here, we use PacBio HiFi and chromosome conformation capture (Omni-C) technologies to generate a chromosome-level, haplotype-resolved genome assembly for white clover totaling 998 Mbp (scaffold N50 = 59.3 Mbp) and 1 Gbp (scaffold N50 = 58.6 Mbp) for haplotypes 1 and 2, respectively, with each haplotype arranged into 16 chromosomes (8 per subgenome). We additionally provide a functionally annotated haploid mapping assembly (968 Mbp, scaffold N50 = 59.9 Mbp), which drastically improves on the existing reference assembly in both contiguity and assembly accuracy. We annotated 78,174 protein-coding genes, resulting in protein BUSCO completeness scores of 99.6% and 99.3% against the embryophyta_odb10 and fabales_odb10 lineage datasets, respectively.


Chain conformation in thin polymer layers as revealed by simulations of ideal random walks.
A confinement-induced mode was discovered in thin cis-1,4-polyisoprene (PI) layers if the film thickness becomes comparable with the size of the PI coil (A. Serghei, F. Kremer, to be published in Phys. Rev. Lett.). It was assigned to the fluctuation of the terminal subchains which are formed by the immobilization of chain segments at the contact with a confining interface. In the present paper we discuss the results of simulations done in order to gain an additional insight into the nature of this novel relaxation process. It turns out that the simulations of the chains as pinned random walks reproduce most of the essential features observed in the experiment.


Promoter analysis of the chalcone synthase (chsA) gene of Petunia hybrida: a 67 bp promoter region directs flower-specific expression.
In order to scan the 5' flanking region of the chalcone synthase (chs A) gene for regulatory sequences involved in directing flower-specific and UV-inducible expression, a chimaeric gene was constructed containing the chs A promoter of Petunia hybrida (V30), the chloramphenicol acetyl transferase (cat) structural sequence as a reporter gene and the chs A terminator region of Petunia hybrida (V30). This chimaeric gene and 5' end deletions thereof were introduced into Petunia plants with the help of Ti plasmid-derived plant vectors and CAT activity was measured. A 220 bp chs A promoter fragment contains cis-acting elements conferring flower-specific and UV-inducible expression. A promoter fragment from -67 to +1, although at a low level, was still able to direct flower-specific expression but could not drive UV-inducible expression in transgenic Petunia seedlings. Molecular analysis of binding of flower nuclear proteins to chs A promoter fragments by gel retardation assays showed strong specific binding to the sequences from -142 to +81. Promoter sequence comparison of chs genes from other plant species, combined with the deletion analysis and gel retardation assays, strongly suggests the involvement of the TACPyAT repeats (-59 and -52) in the regulation of organ-specificity of the chs A gene in Petunia hybrida. We also describe an in vitro organ-specific transient expression system, in which flower or purple callus protoplasts are used, that enables us to pre-screen organ-specific expression of a chimaeric reporter gene.


Growth monitoring of greenhouse lettuce based on a convolutional neural network.
Growth-related traits, such as aboveground biomass and leaf area, are critical indicators to characterize the growth of greenhouse lettuce. Currently, nondestructive methods for estimating growth-related traits are subject to limitations in that the methods are susceptible to noise and heavily rely on manually designed features. In this study, a method for monitoring the growth of greenhouse lettuce was proposed by using digital images and a convolutional neural network (CNN). Taking lettuce images as the input, a CNN model was trained to learn the relationship between images and the corresponding growth-related traits, i.e., leaf fresh weight (LFW), leaf dry weight (LDW), and leaf area (LA). To compare the results of the CNN model, widely adopted methods were also used. The results showed that the values estimated by CNN had good agreement with the actual measurements, with R2 values of 0.8938, 0.8910, and 0.9156 and normalized root mean square error (NRMSE) values of 26.00, 22.07, and 19.94%, outperforming the compared methods for all three growth-related traits. The obtained results showed that the CNN demonstrated superior estimation performance for the flat-type cultivars of Flandria and Tiberius compared with the curled-type cultivar of Locarno. Generalization tests were conducted by using images of Tiberius from another growing season. The results showed that the CNN was still capable of achieving accurate estimation of the growth-related traits, with R2 values of 0.9277, 0.9126, and 0.9251 and NRMSE values of 22.96, 37.29, and 27.60%. The results indicated that a CNN with digital images is a robust tool for the monitoring of the growth of greenhouse lettuce.


Degradation of polyurethane by Aspergillus flavus (ITCC 6051) isolated from soil.
The present study deals with the isolation of fungi from soil with the ability to degrade polyurethane (PU). A pure fungal isolate was analyzed for its ability to utilize PU as a sole carbon source in shaking culture for 30 days. Incubation of PU with Aspergillus flavus resulted in 60.6% reduction in weight of PU. The scanning electron microscopy and Fourier transform infrared spectroscopy (FTIR) results showed certain changes on the surface of PU film and formation of some new intermediate products after polymer breakdown. Thermogravimetric curves showed changes between the thermal behavior of the samples that were inoculated with A. flavus and control. FTIR spectra showed detectable changes in control and incubated samples, suggesting that degradation occurs, with the decreased intensity of band at 1,715 cm(-1), corresponding to ester linkages. We have identified an extracellular esterase activity which might be responsible for the polyurethanolytic activity.


Targeted Identification of Rice Grain-Associated Gene Allelic Variation Through Mutation Induction, Targeted Sequencing, and Whole Genome Sequencing Combined with a Mixed-Samples Strategy.
The mining of new allelic variation and the induction of new genetic variability are the basis for improving breeding efficiency. In this study, in total, 3872 heavy ion-irradiated M2 generation rice seeds and individual leaves were collected. The grain length was between 8 and 10.22 mm. The grain width was between 1.54 and 2.87 mm. The results showed that there was extensive variation in granulotype. The allelic variation in GS3 and GW5 was detected in 484 mixed samples (8:1) using targeted sequencing technology, and 12 mixed samples containing potential mutations and 15 SNPs were obtained; combined with Sanger sequencing and phenotype data, 13 key mutants and their corresponding SNPs were obtained; protein structural and functional analysis of key mutants screened out 6 allelic variants leading to altered grain shape, as well as the corresponding mutants, including long-grain mutants GS3-2 and GS3-7, short-grain mutants GS3-3 and GS3-5, wide-grain mutant GW5-1 and narrow-grain mutant GW5-4; whole genome sequencing identified new grain length gene allelic variants GS3-G1, GS3-G2 and GS3-G3. Based on the above studies, we found 6 granulotype mutants and 9 granulotype-related allelic variants, which provided new functional gene loci and a material basis for molecular breeding and genotype mutation and phenotype analysis. We propose a method for targeted identification of allelic variation in rice grain type genes by combining targeted sequencing of mixed samples and whole genome sequencing. The method has the characteristics of low detection cost, short detection period, and flexible detection of traits and genes.


Correction: Association of birth weight with corneal power in early adolescence: Results from the National Health and Nutrition Examination Survey (NHANES) 1999-2008.
[This corrects the article DOI: 10.1371/journal.pone.0186723.].


Posaconazole : a review of its use in the prophylaxis of invasive fungal infections.
Posaconazole is a second-generation triazole antifungal agent with a broad spectrum of activity that includes Aspergillus spp., Candida spp. and the Zygomycetes. In the US, posaconazole oral suspension administered three times daily is indicated for prophylaxis against invasive Aspergillus and Candida infections in patients aged > or =13 years who are at high risk of developing these infections because of immunosuppression, such as haematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD), or those with haematological malignancies with prolonged neutropenia as a result of chemotherapy. EU-approved prophylactic indications for posaconazole are similar to those in the US. Posaconazole provided effective prophylaxis against invasive fungal infections and was generally well tolerated in two large, well designed trials in HSCT recipients with GVHD, or patients receiving induction-remission chemotherapy for acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) that was expected to result in prolonged neutropenia. It offers coverage of clinically relevant pathogens and is potentially associated with fewer drug-drug interactions than other licensed triazole antifungal agents. Its usefulness in some patients may be limited by the lack of an intravenous formulation, although one is currently being developed. As with other antifungal agents, concerns remain regarding the potential emergence of resistance to broad-spectrum antifungal prophylaxis with posaconazole. Despite this, posaconazole is a valuable emerging option for use as prophylaxis against invasive fungal infections in immunocompromized patients who are at high risk of developing these infections.


Prevalence of systemic sclerosis in Colombia: Data from the National Health Registry 2012-2016.
Systemic sclerosis is an autoimmune disease that characteristically presents with fibrosis and vasculopathy. In Latin America, the information on the epidemiology of this disease is scarce and records are essential to know its behavior in the populations. In Colombia, the Ministry of Health uses the SISPRO tool to collect information on the unified national health system which offers nearly universal coverage (around 95%). This public information makes it possible to perform epidemiological studies on different diseases. Using the SISPRO data corresponding to the years 2012-2016, we analyzed the prevalence and characteristics of patients with systemic sclerosis. A descriptive cross-sectional study was performed based on the SISPRO data; we used as keywords the diagnoses of the International Classification of Diseases related to the diagnosis of systemic sclerosis. A total of 11,300 individuals diagnosed with systemic sclerosis were documented. The estimated prevalence was 23.7 cases per 100,000 inhabitants (based on a total population of 47,663,162); this disease is more frequent in the age group of 65-69 years in females (77%), and has a female:male ratio of 3.27:1. This study describes the epidemiological characteristics of systemic sclerosis in Colombia, based on official statistics from the Ministry of Health. The results provide a new vision of this disease in Latin America and open the door to future research, in order to better understand the particular characteristics of this disease in our country and our region.


The normal width of the adult hip joint: the relationship to age, sex, and obesity.
The articular cartilage thickness of the weight-bearing segment of the hip joint, in standard pelvic radiography, of 240 male and female subjects between the ages of 45-84 years was measured in a random sample of a Jerusalem population. The average value was approximately 4.0 mm and no sex or age difference was found. There was no correlation either between joint width and body build as estimated by the weight to height ratio. It is thus concluded that a narrow joint space should not be expected either in elderly or obese subjects other than as a concomitant finding of arthritic change.


Fumonisin B1 induces autophagic cell death via activation of ERN1-MAPK8/9/10 pathway in monkey kidney MARC-145 cells.
Mycotoxins are secondary fungal metabolites that are capable of inducing a variety of toxic effects in animals and humans resulting from the consumption of the contaminated food. Understanding the mechanisms of the toxicities behind these mycotoxins is required to develop mechanism-based approach to counteract their toxic potential. Fumonisin B1 (FB1) is the most prevalent member of fumonisins that are a group of mycotoxins produced primarily by Fusarium verticillioides and Fusarium proliferatum. Kidney is one of the primary target organs for FB1 action. Using monkey kidney MARC-145 cells as an intro model, we found that FB1 induced caspase-independent programmed cell death accompanied with autophagy induction. Inhibition of autophagy by either chemical inhibitors or RNAi approach led to a significant reduction in cell death by FB1 exposure, indicating possible involvement of autophagy-mediated cell death in nephrotoxicity of FB1. Further mechanistic investigation revealed that activation of ERN1-MAPK8/9/10 axis played a critical role in autophagy induction and autophagy-mediated cell death by FB1 exposure. In addition, we demonstrated that disruption of sphingolipid metabolism was an apical event in FB1-induced ERN1-MAPK8/9/10-mediated autophagic cell death in MARC-145 cells. Lastly, we identified curcumin, a naturally occurring plant phenolic compound, as a possible anti-FB1 agent that can be used to protect kidney cells from FB1-induced cell death through inhibition of MAPK8/9/10 activation.


Chronic direct renin inhibition with aliskiren prevents the development of hypertension in Cyp1a1-Ren2 transgenic rats with inducible ANG II-dependent hypertension.
This study was performed to determine whether chronic direct renin inhibition can prevent the development of slowly progressive angiotensin (ANG) II-dependent hypertension and the associated derangements in renal function in Cyplal-Ren2 transgenic rats with inducible expression of the Ren2 gene. Male Cyplal-Ren2 rats (n = 6) were fed a normal diet containing 0.15% indole-3-carbinol (I3C) for 16 days to induce slowly progressive ANG II-dependent hypertension. Conscious systolic blood pressure was measured daily using tail-cuff plethysmography. The rats were then anesthetized with pentobarbital sodium and surgically prepared for the measurement of mean arterial pressure (MAP) and renal hemodynamics and excretory function. In rats induced with I3C, systolic blood pressure increased by day 3 (130 ± 7-160 ± 5 mm Hg, P < 0.01) and continued to increase to 191 ± 6 mm Hg (P < 0.001) by day 16. In a separate group of rats (n = 6), chronic administration of the direct renin inhibitor, aliskiren (30 mg/kg/d, sc), prevented the development of hypertension (113 ± 5 versus 114 ± 5 mm Hg, not significant). Rats treated with aliskiren exhibited significantly lower mean arterial pressure (138 ± 4 versus 201 ± 6 mm Hg, P < 0.001), renal vascular resistance (23 ± 4 versus 38 ± 3 mm Hg/mL/min · g, P < 0.01), urine flow (17.6 ± 1.4 versus 25.1 ± 2.9 μL/min, P < 0.05) and urinary sodium excretion (1.11 ± 0.32 versus 2.35 ± 0.28 μEq/min, P < 0.05) and higher renal plasma flow (4.22 ± 0.23 versus 2.56 ± 0.21 mL/min · g, P < 0.01) and glomerular filtration rate (1.19 ± 0.07 versus 0.78 ± 0.08 mL/min · g, P< 0.01), compared with induced rats not treated chronically with aliskiren. The present findings demonstrate that chronic direct renin inhibition with aliskiren prevents the development of ANG II-dependent hypertension and the associated derangements in renal hemodynamics and excretory function in Cyplal-Ren2 transgenic rats.


The MarR family transcription factor Rv1404 coordinates adaptation of Mycobacterium tuberculosis to acid stress via controlled expression of Rv1405c, a virulence-associated methyltransferase.
Coordinated regulation of gene expression is essential for pathogen adaptation in vivo. Understanding the control of these virulence circuits in the TB pathogen Mycobacterium tuberculosis is a key challenge if we are to increase our basic understanding of how this organism establishes infection. In this study we focused on the transcriptional regulator Rv1404 that shows similarity to the MarR family of transcriptional repressors. Rv1404 derepresses a set of genes in vivo that have been implicated in virulence and may therefore allow adaptation of M. tuberculosis to the intracellular environment. We used a combination of ChIP-qPCR and Electromobility Band Shift Assays (EMSA) to show that Rv1404 coordinates gene expression in response to stresses such as low pH in M. tuberculosis. Two genes regulated by Rv1404, rv1403c and rv1405c, encode putative SAM-dependent methyltransferases. To elucidate gene function, M. tuberculosis rv1403c and rv1405c mutants were constructed. The mutants showed attenuated growth in response to in vitro stress conditions that mimic the intracellular milieu. Our data sheds new light on the function of a novel regulon controlled by Rv1404 that coordinates adaptation of M. tuberculosis to the in vivo environment and reveals the Rv1405c and Rv1403c methyltransferases as playing a role in this adaptive process.


Giant coronary sinus and a review of the literature.
We report a case of persistent left superior caval vein whom presented with angina pectoris and exertional dyspnea. Echocardiography showed wall motion disturbances with an ejection fraction of 40% and a very large coronary sinus. Our case is a very rare case with a very large coronary sinus presented with angina pectoris.


Monoclonal antibodies against the major zymosan-induced chemotactic factor in rabbit serum.
The major zymosan-induced chemotactic factor in rabbit serum was purified by a two-step ion exchange chromatography procedure. The purified chemoattractant was used as antigen for production of murine monoclonal antibodies against the major chemotactic factor. The primary screening of the hybridoma cultures was an indirect ELISA using purified chemotactic factor as antigen. The final selection among ELISA-positive clones was performed according to the results obtained in a chemotactic inhibition assay. Six monoclonal antibodies were raised. These antibodies completely abrogated or substantially reduced the chemotactic activity in crude zymosan-activated serum. The chemotactic factor(s) could be absorbed onto an immunosorbent column containing monoclonal antibody and subsequently be specifically eluted with acid. By Western blot analysis the molecular weight of the major chemotactic factor was estimated to be approximately 15,000, and isoelectric focusing indicated a pI of about 9.4.


Improved motion correction capabilities for fast spin echo T1 FLAIR propeller using non-cartesian external calibration data driven parallel imaging.
Patient motion is a common challenge in the clinical setting and fast spin echo longitudinal relaxation time fluid attenuating inversion recovery imaging method with motion correction would be highly desirable. The motion correction provided by transverse relaxation time- and diffusion-weighted periodically rotated overlapping parallel lines with enhanced reconstruction methods has seen significant clinical adoption. However, periodically rotated overlapping parallel lines with enhanced reconstruction with fast spin echo longitudinal relaxation time fluid attenuating inversion recovery-weighting has proved challenging since motion correction requires wide blades that are difficult to acquire while also maintaining short echo train lengths that are optimal for longitudinal relaxation time fluid attenuating inversion recovery-weighting. Parallel imaging provides an opportunity to increase the effective blade width for a given echo train lengths. Coil-by-coil data-driven autocalibrated parallel imaging methods provide greater robustness in the event of motion compared to techniques relying on accurate coil sensitivity maps. However, conventional internally calibrated data-driven parallel imaging methods limit the effective acceleration possible for each blade. We present a method to share a single calibration dataset over all imaging blades on a slice by slice basis using the APPEAR non-cartesian parallel imaging method providing an effective blade width increase of 2.45×, enabling robust motion correction. Results comparing the proposed technique to conventional cartesian and periodically rotated overlapping parallel lines with enhanced reconstruction methods demonstrate a significant improvement during subject motion and maintaining high image quality when no motion is present in normal and clinical volunteers.


Determinants of LA reservoir strain: Independent effects of LA volume and LV global longitudinal strain.
Left atrial (LA) deformation during the reservoir phase (LASr) has demonstrated strong prognostic value in different clinical settings. Although determinants of left atrial reservoir strain including left atrial relaxation, left atrial compliance, and left ventricular longitudinal systolic function are fairly well defined, there is incomplete information regarding the effect of left atrial volume on this relationship which is the focus of our study. Consecutive patients without prior cardiac disease referred for transthoracic echocardiography were prospectively recruited. All participants underwent clinical assessment, transthoracic echocardiography (TTE), and screening exercise stress test. Only patients with normal left ventricular ejection fraction (LVEF) without left ventricular hypertrophy (LVH) or myocardial ischemia on stress testing were included. A total of 260 patients (57% male, mean age 59 ± 14 years) were included. 70% had hypertension, 33% had diabetes mellitus, and 31% had both HTN and DM. On multivariate analysis, age, e', LAVI, and LV GLS (P < .01 for all) showed an independent association with LASr. Of interest, at lower tertiles of LAVI, a linear decrease in LASr was observed parallel to worsening LV GLS, whilst at higher tertiles of LAVI, the reduction in LASr was non-linear implying that LA enlargement, consequent to LA remodeling, had an incremental effect on LASr. Age, e', LV GLS, and LAVI were independently associated with LASr. LA remodeling reflected by larger LAVI had an incremental negative association with LASr independent of LV GLS.


Effects of different protein and lipid levels on the growth performance and intestinal microflora of loach (Paramisgurnus dabryanus).
The aim of this study was to examine the effects of dietary protein and lipid levels on the growth performance and homeostasis of the intestinal flora in Paramisgurnus dabryanus. An 8-wk 3 × 3 two-factorial experiment was conducted to investigate the interaction between dietary crude protein (CP: 30%, 35%, 40%) and ether extract (EE: 6%, 10%, 14%) on the growth rate and the intestinal microflora of P. dabryanus. A total of 2,160 fish (5.19 ± 0.01 g) were randomly allotted to 36 aquariums each with 60 fish. Fish were fed the experimental diet twice daily. Results revealed that weight gain rate (WGR), specific growth rate (SGR), protein efficiency ratio and net protein utilization significantly increased when increasing protein levels from 30% to 40% (P < 0.05). Both WGR and SGR enhanced first but reduced thereafter with maximum value at 10% lipid level as dietary lipid increased from 6% to 14% (P < 0.05). Significant interactions between protein and lipid were found with feed conversion rate, lipid efficiency ratio and net lipid utilization (P < 0.05). At the phylum level, Proteobacteria and Actinobacteria were the dominant bacteria; at the genus level, Burkholderia-Caballeronia-Paraburkholderia was the dominant bacteria. Fish fed the diet containing 10% lipid had a higher abundance of Proteobacteria and unclassified_f_Eenterobacteriaceae than those fed the 14% lipid diet, and a higher abundance of Rhodobacter than those fed the 6% lipid diet (P < 0.05). Analysis of the predicted functions showed that metabolism in the intestine of fish in the CP40EE10 group was more active than that in CP30EE14 group. Polynomial regression analysis found that a diet containing 40.87% protein and 9.88% lipid can be considered optimal for P. dabryanus.


The effects of theophylline and choleragen on sodium and chloride ion movements within isolated rabbit ileum.
1. Theophylline (10 mM) and choleragen change the direction of net Cl- movements across rabbit ileum, in the short-circuit current condition, from absorption to secretion. The specific activity ratio R of Cl- tracers within the tissue coming from mucosal and serosal solutions respectively is increased, which is consistent with an increase in Cl- exchange flux across the mucosal border. 2. Net Na+ movement is also changed from net absorption to secretion by theophylline and choleragen; the specific activity ratio R of Na+ tracers is raised by theophylline. Because of the large paracellular component to transepithelial Na+ movements, an increase in Na+ exchange flux across the mucosal border is not detected. 3. 2,4,6-Triaminopyrimidine (20 mM) which has been previously shown to block paracellular Na+ movements, blocks both the theophylline and choleragen-dependent reversal of net Na+ movement by preventing the decrease in m-s Na flux. The theophylline-dependent increase in the ratio R of Na+ is still present, and is consistent with an increase in Na+ exchange flux across the mucosal border--unmasked by removal of the paracellular flux components. 4. Ouabain (0.1 mM) abolishes net absorption of Na+ and Cl- in control and net secretion of Na+ and Cl- in theophylline-treated tissue. Ouabain does not affect the theophylline-dependent increase in Cl- exchange across the mucosal border. 5. Replacement of Ringer Cl- with SO24- or Na+ by choline prevents the effects of theophylline and choleragen on Na+ and Cl- fluxes respectively. 6. Ethacrynate (0.1 mM) prevents the theophylline-dependent effects on net Na+ movement. Raising ethacrynate to 0.2 mM abolishes the effects of theophylline on Cl- exchange. An interpretation of these results is that theophylline and choleragen raise the Cl- permeability of the brush border. This increases NaCl leakage from the hypertonic lateral intercellular space into the mucosal solution thereby causing secretion. The selective action of triaminopyrimidine and ethacrynate (0.1 mM) on Na+ flux indicates that Na+ and Cl- move via separate transport pathways across the mucosal border.


Pretreatment with EDU decreases rat lung cellular responses to ozone.
The phenylurea compound EDU (N-[2-(2-oxo-1-imidazolindinyl)ethyl]-N'-phenylurea) has been shown to protect plants from the damaging effects of ozone exposure. Models of rat lung injury, based on acute exposure to 2 ppm ozone for 3 hr and on exposure to 0.85 ppm ozone for 2 days, were used to determine whether EDU pretreatment of rats protected lungs from oxidant injury. Rats were pretreated with 100 mg/kg body wt EDU by ip administration for 2 days prior to and on the days of ozone exposure. No adverse toxicological effects of EDU pretreatment were observed. Lung superoxide dismutase (SOD) and catalase (CAT) activities were significantly enhanced from 636 to 882 U/lung and from 599 to 856 U/lung, respectively. One day following acute exposure (2 ppm for 3 hr), an ozone-induced increase of polymorphonuclear leukocytes (PMNs) from 0.01 to 1.18 million cells/lung was decreased to 0.68 million by EDU pretreatment. No alteration occurred in the degree of lung permeability indicated by increased lavage fluid albumin. EDU pretreatment also significantly decreased ozone-induced increases in PMN recovery after 2 days exposure to 0.85 ppm ozone from 5.54 to 2.12 million cells/lung. However, in this second case, EDU pretreatment reduced the observed ozone damage, indicated by a decrease in lavage fluid albumin and by a decrease in the macrophage and lymphocyte infiltration associated with this length of ozone exposure. The observation that EDU-treated cultured pulmonary arterial endothelial cells increased SOD and CAT activities identified a potential lung site of EDU interaction. These data demonstrated that although EDU pretreatment appears not to prevent initial ozone damage, it does reduce the infiltration of PMNs and might therefore prevent amplification of the injury associated with this cell type.


EcircPred: Sequence and secondary structural property based computational identification of exonic circular RNAs.
Circular RNAs are new class of stable non-coding RNAs, whose expressions are specific to tissues as well as developmental stages and reported to act as gene regulators. Conspicuous presences of some of them as biomarkers for cancers, aging etc. are well reported. Biogenesis of circular RNA competes with Pre-mRNA splicing using the same splicing machinery and gene loci. Also, some circular RNAs are reported to have open reading frames and internal ribosome entry site for ribosome binding, which increases the chance of overlapping features among circular and mRNA transcripts. Therefore, discriminating the Exonic circular RNAs and mRNAs solely through sequence properties is challenging. However, possible discriminating factors, such as, reports on non-canonical arrangement of exons in circular RNAs were cited. This study was dedicated to classify Circular RNAs from mRNAs by recruiting features extracted from sequences as well as predicted secondary structures and ANN classifier models for all these feature types. The features were statistics of di-nucleotide index, emission probability of RNA sequences and entropy of di-nucleotides. Finally a simple decision voting was applied to combine decisions obtained from multiple classifiers. After performing 10 fold cross validation we obtained average values of efficiency, sensitivity, specificity and Mathews correlation coefficient as 0.8374, 0.8544, 0.8203 and 0.6753 respectively. In the backdrop of few reports of identification of circular RNAs from constitutive exons and other long non-coding RNAs, this is the first report of discriminating exonic circular RNAs from mRNAs using sequence and sequence-derived properties.


The metronomic combination of paclitaxel with cholinergic agonists inhibits triple negative breast tumor progression. Participation of M2 receptor subtype.
Triple negative tumors are more aggressive than other breast cancer subtypes and there is a lack of specific therapeutic targets on them. Since muscarinic receptors have been linked to tumor progression, we investigated the effect of metronomic therapy employing a traditional anti-cancer drug, paclitaxel plus muscarinic agonists at low doses on this type of tumor. We observed that MDA-MB231 tumor cells express muscarinic receptors, while they are absent in the non-tumorigenic MCF-10A cell line, which was used as control. The addition of carbachol or arecaidine propargyl ester, a non-selective or a selective subtype 2 muscarinic receptor agonist respectively, plus paclitaxel reduces cell viability involving a down-regulation in the expression of ATP "binding cassette" G2 drug transporter and epidermal growth factor receptor. We also detected an inhibition of tumor cell migration and anti-angiogenic effects produced by those drug combinations in vitro and in vivo (in NUDE mice) respectively. Our findings provide substantial evidence about subtype 2 muscarinic receptors as therapeutic targets for the treatment of triple negative tumors.


On the mechanism and site of action of enkephalin on single myenteric neurons.
Intracellular recordings were made from neurons in the isolated myenteric plexus of the guinea-pig ileum. Methionine- and leucine-enkephalin were applied to the neurons either by adding them to the perfusing solution in known concentrations or be ejecting them by microiontophoresis. When applied in the perfusion solution, the enkephalin (1 nM-1micron) hyperpolarized the soma membrane of less than half the neurons. The hyperpolarization was of rapid onset and reversed fully when the enkephalin was washed out; in a proportion of cells the hyperpolarization was associated with a fall in neuronal input resistance. This hyperpolarization was reversed or prevented by naloxone. When applied by iontophoresis to the soma membrane, enkephalin never hyperpolarized the myenteric neurons. Hyperpolarization in response to iontophoretic application of enkephalin was observed only when the enkephalin was applied to the surface of the ganglion away from the soma membrane; such hyperpolarization was prevented by addition of naloxone to the perfusion solution. The results indicate that the site at which enkephalin causes the naloxone-reversible hyperpolarization is not the soma membrane. The possibility is discussed that enkephalin may cuase presynaptic inhibition in this preparation by hyperpolarizing or increasing the conductance sites on the cellular processes from which acetylcholine is released.


Real-time multispectral transmission of hard tooth tissues and dental composites with their heating.
The objective of the study was to investigate the real-time transmission of Violet, Blue, Red and Near Infra-Red (NIR) irradiation through 2 or 4 mm thick dental composites and tooth tissue samples at varying positions of Light Curing Unit (LCU) with polymerization temperature monitoring. The composites tested were: Filtek Universal Restorative (FUR), Filtek One Bulk Fill (FBF), Tetric EvoCeram (TEC), Tetric Bulk Fill (TBF) and Tetric PowerFill (TPF). The new LCU Pinkwave (a four-wavelength source manufactured by Vista Apex, USA) was placed either centrally or eccentrically for 3 mm above the sample. A Fiber spectrometer detected irradiation and Infrared Thermal camera polymerization temperatures. All eccentric LCU positions significantly weaken transmitted spectra for all composites in both thickness, jeopardizing Blue light. The LCU position did not affect transmitted irradiation for tooth tissues. The reduction in wavelength intensity when penetrating through thicker compared to thinner composite samples was 62%, 50% and 31% for Blue, NIR and Red, respectively, and 90%, 50% and 35% for tooth tissue samples, respectively. The temperature of bulk fill composites with additional photoinitiators rises faster. Eccentric LCU positions cause a significant decrease in both speed and the maximal value of temperature rise. Red and NIR irradiations contribute to the polymerization temperature. Tested LCU source cause considerable inhomogeneity in the emitted and transmitted spectra. Tooth tissues homogenize irradiation, but drastically attenuates it. Red light has better potential than Blue light concerning penetration and could be further investigated as the wavelength for activation of an adjusted photoinitiator.


[Pondering in-situ induction of endogenous neural stem cells in hippocampus of rats with Alzheimer disease by acupuncture].
Analysis of domestic and overseas literature on the relationship between Alzheimer disease (AD) and neural stem cells (NSC) shows that inducing the proliferation and differentiation of hippocampal endogenous NSC in-situ by acupuncture is probably the mechanism of acupuncture therapy in treating AD, and that it may further improve the method for the research on AD.


Intraoral midline mandibulotomy improves laryngeal access for transoral resection of laryngeal cancer.
Intraoral midline mandibulotomy is a technique that can be used to increase exposure for transoral endoscopic laser microsurgery (TLS). We describe the case of a 51 year old male with persistent T1 glottic carcinoma. At initial diagnosis, he had been referred for curative radiotherapy as laryngeal access was not sufficient for TLS. For treatment of his recurrence, we describe the technique of performing a midline mandibular osteotomy to improve access to the larynx allowing for safe and effective transoral endoscopic laser microsurgery. Surgical access to the larynx was greatly improved, and we were able to perform TLS in a case that would have otherwise not been amenable to TLS. An intraoral midline mandibulotomy can improve access to the larynx and allow for successful transoral resection of laryngeal cancer in patients with otherwise inaccessible tumors.


Imaging of cysts and bursae about the knee.
Cystic lesions are common around the knee and are often encountered as an incidental finding on routine magnetic resonance imaging examinations. The clinical presentation of cysts and other fluid collections is variable, depending on their size, location, and relationship to adjacent anatomic structures. This article reviews the anatomy, etiology, clinical presentation, and imaging features of commonly occurring cystic lesions around the knee and discusses some of the potential pitfalls that may be encountered in clinical practice.


Primate enamel evinces long period biological timing and regulation of life history.
The factor(s) regulating the combination of traits that define the overall life history matrix of mammalian species, comprising attributes such as brain and body weight, age at sexual maturity, lifespan and others, remains a complete mystery. The principal objectives of the present research are (1) to provide evidence for a key variable effecting life history integration and (2) to provide a model for how one would go about investigating the metabolic mechanisms responsible for this rhythm. We suggest here that a biological rhythm with a period greater than the circadian rhythm is responsible for observed variation in primate life history. Evidence for this rhythm derives from studies of tooth enamel formation. Enamel contains an enigmatic periodicity in its microstructure called the striae of Retzius, which develops at species specific intervals in units of whole days. We refer to this enamel rhythm as the repeat interval (RI). For primates, we identify statistically significant relationships between RI and all common life history traits. Importantly, RI also correlates with basal and specific metabolic rates. With the exception of estrous cyclicity, all relationships share a dependence upon body mass. This dependence on body mass informs us that some aspect of metabolism is responsible for periodic energy allocations at RI timescales, regulating cell proliferation rates and growth, thus controlling the pace, patterning, and co-variation of life history traits. Estrous cyclicity relates to the long period rhythm in a body mass-independent manner. The mass-dependency and -independency of life history relationships with RI periodicity align with hypothalamic-mediated neurosecretory anterior and posterior pituitary outputs. We term this period the Havers-Halberg Oscillation (HHO), in reference to Clopton Havers, a 17th Century hard tissue anatomist, and Franz Halberg, a long-time explorer of long-period rhythms. We propose a mathematical model that may help elucidate the underlying physiological mechanism responsible for the HHO.


On the relationship between long-distance and heterogeneous electron transfer in electrode-grown Geobacter sulfurreducens biofilms.
The ability of certain microorganisms to live in a multi-cell thick, electrode-grown biofilm by utilizing the electrode as a metabolic electron acceptor or donor requires electron transfer across cell membranes, through the biofilm, and across the biofilm/electrode interface. Even for the most studied system, anode-grown Geobacter sulfurreducens, the mechanisms underpinning each process and how they connect is largely unresolved. Here we report on G. sulfurreducens biofilms grown across the gap separating two electrodes by maintaining one electrode at 0.300V vs. Ag/AgCl (0.510V vs. SHE) to act as a sustained metabolic electron acceptor while the second electrode was at open circuit. The poised electrode exhibited the characteristic current-time profile for electrode-dependent G. sulfurreducens biofilm growth. The open circuit potential (OCP) of the second electrode however increased after initially decreasing for 1.5-2days. The increase in OCP is taken to indicate the point at which the growing biofilm bridged the gap between the electrodes, enabling cells in contact with the open circuit electrode to utilize the poised electrode as an electron acceptor. After but not prior to reaching this point, the second electrode was able to act as a sustainable electron acceptor immediately after being placed under potential control without requiring further time to develop. These results indicate that heterogeneous ET (H-ET) across the biofilm/electrode interface and long-distance ET (LD-ET) through the biofilm are highly correlated, if not inseparable, and may share many common components.


Novel N-acetyl-Glycol-split heparin biotin-conjugates endowed with anti-heparanase activity.
Heparanase is regarded as a promising target for anticancer drugs and Ronepastat is one of the most promising heparanase inhibitors insert in clinical study for Multiple Myeloma Therapy. To improve its pharmacokinetic/pharmacodynamic profile, as well to have an antidote able to neutralize its activity in case of over dosages or intolerance, a new class of its derivatives was obtained inserting non-carbohydrate moieties of different length between the polysaccharide chain and biotin or its derivatives. In vitro these novel derivatives maintain the anti-heparanase activity without induced toxicity. The newly synthesized compounds retained the ability to attenuate the growth of CAG myeloma tumors in mice with potency similar, or in one case even higher than that of the reference compound Roneparstat as well as inhibited metastatic dissemination (lung colonization) of murine B16-F10 melanoma cells in vivo.


An evaluation of the production effects of video self-modeling.
A multiple baseline across tasks design was used to evaluate the production effects of video self-modeling on three activities of daily living tasks of an adult male with Autism Spectrum Disorder and Intellectual Disability. Results indicated large increases in task accuracy after the production of a self-modeling video for each task, but before the video was viewed by the participant. Results also indicated small increases when the participant was directed to view the same video self-models before being prompted to complete each task.


Influence of age on the renal renin response to a high salt intake in the rat.
Saline drinking combined with DOCA-treatment was found to decrease renal renin in weanlings at a higher rate than in adult rats, with a comparable saline consumption level. The decrease was not potentiated by uninephrectomy.


The effect of biodiesel production method on its combustion behavior in an agricultural tractor engine.
In this study, biodiesel fuel was produced from waste cooking oil (WCO) using a heterogeneous catalyst under microwave (MB) and conventional (CB) heating, and fueled in an agricultural tractor engine to evaluate the engine performance as well as emissions. The biodiesels presented different fatty acid methyl ester (FAME) profiles where MB had lower unsaturated FAME chains. Beyond the transesterification reaction time, the energy consumed for MB biodiesel production diminished by around eight times compared to that required for CB production. The engine results confirmed the positive influence of blending net diesel fuel with biodiesel for enhancing the engine performance and reducing the emissions. More than 20% increment in the engine power and torque was detected at all engine loads (the engine speed was adjusted at 1500 rpm). The hydrocarbon (HC), carbon monoxide (CO), and smoke opacity (SO) indicated significant reductions compared to when net diesel fuel was used. According to statistical analysis, CB25 and MB25 fuels presented a suitable combination as fuel where MB25 provided better engine performance, lower HC and SO emissions, with CO emissions reaching the minimum amount by CB fuels.


Leukocyte motility in response to neuropeptides is heparan sulfate proteoglycan dependent.
Activation of neuropeptide receptors on leukocytes induces chemotaxis. We determined in Boyden chambers with micropore filters, whether in human monocytes and lymphocytes this migratory response is heparan sulfate proteoglycan (HSPG) dependent. Chemotaxis toward calcitonin gene-related peptide, secretoneurin, vasoactive intestinal peptide (VIP), and substance P (SP) was abolished by removal of heparan sulfate side chains from cell surface proteoglycans or by addition of anti-syndecan-4 antibodies. Inhibition of neuropeptide-induced chemotaxis by dimethyl sphingosine (DMS), an inhibitor of sphingosine kinase, indicates transactivation of the sphingosine-1-phosphate chemotaxis pathway which was previously identified as being syndecan-4-related. Data suggest that HSPGs are involved in neuropeptide-induced chemotaxis of leukocytes.


Walk headache: an unusual manifestation of ischemic heart disease.
A 71 year old man sought neurological advice because for two years he had suffered from headache every time he made an effort. A treadmill stress test showed a relation between effort, headache and depression of ST segments on E.C.G. With isosorbide dinitrate and diltiazem, the manifestations improved. This suggests a referred head pain due to myocardial ischemia.


Socioeconomic Status and Mental Health Service Use Among National Guard Soldiers.
Convergent evidence suggests that low socioeconomic status (SES) may be related to reduced mental health service use. However, this relationship has not been tested in the National Guard (NG) population, in which the prevalence of mental health symptoms is high. Surveys were completed by 1,262 NG soldiers. SES was measured by education and income. Adjusted multivariable regression models assessed associations between SES, overall service use, and use of specific types of services. SES was not associated with overall use but was associated with use of certain types of services. Higher SES was associated with lower likelihood of psychotropic medication use (odds ratio=.83, 95% confidence interval=.72-.96), and higher SES strengthened the positive relationship between PTSD and use of individual therapy. Higher SES may increase the use of individual therapy among soldiers with PTSD. Barriers to care among individuals with low SES merit continued attention and outreach efforts.


First-year experience of transitioning from registered nurse to nurse practitioner.
Transitioning to advanced practice, novice nurse practitioners need to take on new roles, learn new practice areas, and develop new skills. This process requires breaking old practices and work habits and facing new challenges. To explore the nature of nurse practitioners' work experiences during the first year of transition from registered nurse to nurse practitioner. This qualitative study was based on Husserl's phenomenological methodology. A purposive sample of 16 first-year nurse practitioners was recruited. Data were collected through in-depth interviews and analyzed by thematic content analysis. The approaches of Lincoln & Guba were applied to improve the validity of the study. Results showed that the first-year experience of transitioning from registered nurse to nurse practitioner fell into two overarching themes: challenge and adjustment. The challenge consists of five subthemes: "facing the expectation-reality gap," "managing others' expectations," "striving to acquire professional skills," "handling situational variability," and "bearing emotional burdens" subthemes. The adjustment includes five subthemes: "finding resources," "gaining experiences," "building relationships," "relieving stress," and "overcoming obstacles." Novice nurse practitioners face many challenges as they adjust to a new role during their first year on the job. New nurse practitioners develop coping strategies to help themselves adjust to their work. They also gradually gain new resources and experiences to help them stay positive in stressful situations and restore work-life balance. The challenges of transitioning from a registered nurse to a nurse practitioner cannot be overlooked. Novice nurse practitioners need appropriate support measures to adapt to advanced practice roles.


Comprehensive study of nine novel cases of TFEB-amplified renal cell carcinoma: an aggressive tumour with frequent PDL1 expression.
First described in 2014, renal cell carcinoma (RCC) with TFEB amplification (6p21) is a rare molecular subgroup whose diagnosis is challenging. The prognosis and therapeutic implications remain unclear. We report here the clinical, histological, immunohistochemical, and genetic features of nine novel cases. The pathological and immunohistochemical features were centrally reviewed by expert uropathologists. Fluorescence in situ hybridisation (FISH) confirmed the diagnosis and comparative genomic hybridisation (CGH) was performed to determine quantitative genomic alterations. We also performed an exhaustive review of the literature and compiled our data. TFEB-amplified RCC were locally advanced, with initial lymph node involvement in one case and liver metastasis in another case. They were high-grade eosinophilic tumours with papillary/pseudopapillary architecture, frequent positivity for melanocytic markers, and frequent PDL1 expression. FISH demonstrated high-level TFEB amplification in six cases. One case showed concomitant TFEB translocation. CGH analysis identified complex alterations with frequent losses of 1p, 2q, 3p, 6p, and frequent 6p and 8q gains. VEGFA coamplification was identified in all cases with a lower level than TFEB. The prognosis was poor, with five patients having lymph node or distant metastases. TFEB-amplified RCC is a rare molecular subgroup with variable morphology whose diagnosis is confirmed by FISH analysis. The complex alterations identified by CGH are consistent with an aggressive clinical behaviour. The coamplification of VEGFA and the expression of PDL1 could suggest a potential benefit from antiangiogenics and targeted immunotherapy in combination for these aggressive tumours.


Lymphomatosis cerebri: a rare variant of primary central nervous system lymphoma and MR imaging features.
Lymphomatosis cerebri (LC) is a rare variant of primary central nervous system lymphoma (PCNSL), characterized by diffuse infiltration without the formation of a discrete mass. The diagnosis of LC is a challenge because the imaging findings are atypical for lymphoma. The purpose of present study is to investigate MRI characteristics and clinical features of LC and potentially facilitate an early and accurate diagnosis of this often-missed disease. Seven patients (average 44 years, 19-58 years) with LC proved basing on MRI and histology were retrospectively reviewed the clinical data and cerebral MR imaging findings. The common presenting symptoms were cognitive decline, behavioral disturbance, gait disturbance. All patients had both deep and lobar lesion distribution, and two of them had infratentorial involvement. Lack of contrast enhancement and subtle patchy enhanced pattern were observed in two and three patients, respectively. The remaining two patients presented multiple patchy enhancement. Most of the lesions were slightly hyperintense to normal brain on DWI as well as hyperintense on ADC maps. Three patients presented a pattern of marked decrease of NAA/Cr, increase of Cho/Cr, and two of the three cases showed increased Lip/Cr and Lac/Cr on MRS. We conclude that diffuse bilateral lesions especially in deep and lobar region including white and gray matter, without enhancement or with patchy enhancement, marked decrease of NAA/Cr and increase of Cho/Cr, and increased Lip/Cr and Lac/Cr are suggestive of LC. Prompt recognition of these imaging patterns may lead to early diagnosis of LC and brain biopsy with improved prognosis.


The effect of boromycin on the Ca2+ homeostasis.
A boron-containing antibiotic, boromycin (BM), was found to influence the Ca2+ homeostasis in both excitable and non-excitable cells. In non-excitable cells (human erythrocytes and leucocytes) it inhibited the resting passive 45Ca2+ transport in 10(-6)-10(-5) mol/L concentrations. In human erythrocytes, the passive 15Ca2+ transport induced by the presence of 1 mmol/L NaVO3 was inhibited by boromycin (90% inhibition) as well. The inhibitory effect of BM on the NaVO3-induced passive 45Ca2+ transport was diminished in the presence of inhibitory concentrations of nifedipine (10 micromol/L -60% inhibition) or of those of K+o (75 mmol/L -20% inhibition). On the other hand, in rat brain synaptosomes, and rat cardiomyocytes, BM stimulated the passive 45Ca2+ transport in 'resting' cells at similar concentrations. In rat cardiomyocytes the stimulation was transient. The stimulatory effect on the passive 45Ca2+ transport in rat brain synaptosomes was accompanied with the increase of cytoplasmic Ca2+ concentration measured by means of the entrapped fluorescent Ca2+ chelator fura-2. The stimulatory effect of BM was diminished when synaptosomes were pre-treated with veratridine (10 micromol/L) which itself stimulated the passive 45Ca2+ transport. At saturating concentrations of veratridine, no stimulatory effect of BM was observed. These results could be explained by the indirect interaction of BM with both Ca2+ and Na+ transport systems via transmembrane ionic gradients of monovalent cations and could be useful in determining whether the cells belong to excitable, or non-excitable cells.


Understanding leptin-dependent regulation of skeletal homeostasis.
Despite growing evidence for adipose tissue regulation of bone mass, the role of the adipokine leptin in bone remodeling remains controversial. The majority of in vitro studies suggest leptin enhances osteoblastic proliferation and differentiation while inhibiting adipogenic differentiation from marrow stromal cells. Alternatively, some evidence demonstrates either no effect or a pro-apoptotic action of leptin on stromal cells. Similarly, in vivo work has demonstrated both positive and negative effects of leptin on bone mass. Most of the literature supports the idea that leptin suppresses bone mass by acting in the brainstem to reduce serotonin-dependent sympathetic signaling from the ventromedial hypothalamus to bone. However, other studies have found partly or entirely contrasting actions of leptin. Recently one study found a significant effect of surgery alone with intracerebroventricular administration of leptin, a technique crucial for understanding centrally-mediated leptin regulation of bone. Thus, two mainstream hypotheses for the role of leptin on bone emerge: 1) direct regulation through increased osteoblast proliferation and differentiation and 2) indirect suppression of bone formation through a hypothalamic relay. At the present time, it remains unclear whether these effects are relevant in only extreme circumstances (i.e. models with complete deficiency) or play an important homeostatic role in the regulation of peak bone acquisition and skeletal remodeling. Ultimately, determining the actions of leptin on the skeleton will be critical for understanding how the obesity epidemic may be impacting the prevalence of osteoporosis.


The common idiotypic specificity of anti-a2 allotype antibodies: contribution of H and L chains to idiotype expression.
Previously an idiotypic specificity common to anti-a2 allotype Ab from 15 rabbits was detected and characterized. The contribution of H and L chains to the expression of this common idiotypic specificity was determined. Two types of recombinant IgG were prepared: (1) H chains from anti-a2 Ab with L chains from normal a3b4 IgG, and (2) L chains from anti-a2 Ab with H chains from normal a3b4 IgG. By inhibition of binding radioimmunoassay, recombinant IgG having either H or L chains from anti-a2 did not inhibit the binding between anti-a2 Ab and anti-idiotype Ab. By direct binding radioimmunoassay, recombinant IgG of H chains from anti-a2 Ab with L chains from a3b4 IgG reacted with anti-idiotype Ab whereas recombinant IgG with H chains from normal a3b4 IgG and L anti-a2 Ab is determined primarily by the H chain; however, the full expression of the common idiotypic specificity requires the interaction of both H and L chains from anti-a2 Ab.


Microbial Endophytes: Emerging Trends and Biotechnological Applications.
A plethora of knowledge on the role of endophytic microorganisms has been reported in recent years. The cooperative chemistry between the endophytes and the internal host tissue has turned them into a crucial aid for biotechnological applications. Microbial endophytes are ubiquitous among most plant species on earth and contribute to the benefit of host plants by generating a wide range of metabolites that provide the plant with survival value. Endophytes can either directly stimulate plant growth by producing phytohormones or indirectly stimulate plant growth by increasing the availability of soil nutrients to plants. Endophytes may also help suppress diseases in plants directly by neutralizing environmental toxic elements, and by inhibiting plant pathogens by antagonistic action, or indirectly by stimulating induced plant systemic resistance. Several natural compounds produced by endophytes as secondary metabolites are beneficial to both plants and humans. This is why endophytes are regarded as a significant source of novel natural products of value in modern medicine, agriculture, and industry. Endophytes are known for producing pigments, bioactive compounds, and industrially important enzymes, like glucanase, amylase, laccase, etc. Some endophytes can also produce nanoparticles that potentially have numerous applications in a variety of fields. They also play an important role in biodegradation and bioremediation, both of which are beneficial to the environment and ecology. In this review, we highlighted potential biotechnological applications of endophytic microbes, as well as their diverse importance in plant growth and public health.


Is sludge retention time a decisive factor for aerobic granulation in SBR?
This study investigated the role of sludge retention time (SRT) in aerobic granulation under negligible hydraulic selection pressure. Results showed that no successful aerobic granulation was observed at the studied SRTs in the range of 3-40 days. A comparison analysis revealed that hydraulic selection pressure in terms of the minimum settling velocity would be much more effective than SRT for enhancing heterotrophic aerobic granulation in sequencing batch reactor (SBR). It was shown that SRT would not be a decisive factor for aerobic granulation in SBR.


Faculty development for fellows: Developing and evaluating a broad-based career development course for critical care medicine trainees.
There is no defined training experience to teach the broad range of professional skills needed to transition from critical care trainee to practitioner. We hypothesized that a durable set of career development skills could be created for critical care medicine (CCM) trainees using a novel curriculum defined by both learners and content experts. We presented a curriculum focused on professional development skills to 8 second-year CCM fellows at a university-based training program. A needs assessment using input from faculty and fellows selected 22 topics for the course. Surveys given precurriculum and postcurriculum and at 3-year follow-up measured the perceived importance of these topics and learner comfort with the skills presented. Average class attendance was 77%. Seven subjects (87.5%) responded to each survey time point. Comfort scores increased from precourse to postcourse survey. Scores were maintained across most content areas from postcourse survey to follow-up. Respondents attributed a high level of importance to receiving training of this kind. Teaching a broad range of career development skills can result in durable confidence when reinforced by regular use postgraduation. This course fills a critical care educational need, facilitating the transition to practitioner after CCM training.


Aggressive angiomyxoma of the epididymis.
Aggressive angiomyxoma is a rare locally invasive non-metastasizing soft tissue neoplasm that is most commonly located in the female pelvis and perineum. We report a case of aggressive angiomyxoma arising from the epididymis of a young male, which was treated by radical orchiectomy.


Robotic pancreaticoduodenectomy decreases the risk of clinically relevant post-operative pancreatic fistula: a propensity score matched NSQIP analysis.
A single-institution study demonstrated robotic pancreaticoduodenectomy (RPD) was protective against clinically-relevant postoperative pancreatic fistula (CR-POPF) compared to open pancreaticoduodenectomy (OPD). We sought to compare the national rate of CR-POPF by approach. Procedure-targeted pancreatectomy Participant User Data File was queried from 2014 to 2017 for all patients undergoing pancreaticoduodenectomy. A modified fistula risk score was calculated and patients were stratified into risk categories. Multivariate logistic regression and propensity score matching was used. The rate of CR-POPF (15.6% vs. 11.9%; p = 0.026) was higher in OPD compared to RPD. On subgroup analysis, OPD had higher CR-POPF in high risk patients (32.9% vs. 19.4%; p = 0.007). On multivariable analysis OPD was a predictor of increased CR-POPF (Odds Ratio [OR] = 1.61 [1.15-2.25]; p = 0.005). Other operative factors associated with increased CR-POPF included soft pancreatic texture (OR = 2.65 [2.27-3.09]; p < 0.001) and concomitant visceral resection (OR = 1.41 [1.03-1.93]; p = 0.031). Increased duct size (reference <3 mm) was predictive of decreased CR-POPF: 3-6 mm (OR = 0.70 [0.61-0.81]; p < 0.001) and ≥6 mm (OR = 0.47 [0.37-0.60]; p < 0.001). Following propensity score matching, RPD continued to be protective against the occurrence of CR-POPF (OR = 1.54 [1.09-2.17]; p = 0.013). This is the largest multicenter study to evaluate the impact of RPD on POPF. It suggests that RPD can be protective against POPF, especially for high risk patients.


A randomized, multicenter, single-blinded trial comparing paclitaxel-coated balloon angioplasty with plain balloon angioplasty in drug-eluting stent restenosis: the PEPCAD-DES study.
This study sought to define the impact of paclitaxel-coated balloon angioplasty for treatment of drug-eluting stent restenosis compared with uncoated balloon angioplasty alone. Drug-coated balloon angioplasty is associated with favorable results for treatment of bare-metal stent restenosis. In this prospective, single-blind, multicenter, randomized trial, the authors randomly assigned 110 patients with drug-eluting stent restenoses located in a native coronary artery to paclitaxel-coated balloon angioplasty or uncoated balloon angioplasty. Dual antiplatelet therapy was prescribed for 6 months. Angiographic follow-up was scheduled at 6 months. The primary endpoint was late lumen loss. The secondary clinical endpoint was a composite of cardiac death, myocardial infarction attributed to the target vessel, or target lesion revascularization. There was no difference in patient baseline characteristics or procedural results. Angiographic follow-up rate was 91%. Treatment with paclitaxel-coated balloon was superior to balloon angioplasty alone with a late loss of 0.43 ± 0.61 mm versus 1.03 ± 0.77 mm (p < 0.001), respectively. Restenosis rate was significantly reduced from 58.1% to 17.2% (p < 0.001), and the composite clinical endpoint was significantly reduced from 50.0% to 16.7% (p < 0.001), respectively. Paclitaxel-coated balloon angioplasty is superior to balloon angioplasty alone for treatment of drug-eluting stent restenosis. (PEPCAD DES-Treatment of DES-In-Stent Restenosis With SeQuent® Please Paclitaxel Eluting PTCA Catheter [PEPCAD-DES]; NCT00998439).


Ocular dryness assessment in Saudi employees working indoors and outdoors.
To investigate dry eye disease in Saudi employees working in indoor and outdoor environments. A single-center randomized controlled study was carried out in an optometry clinic, to assess the ocular dryness of 24 male employees (12 indoor and 12 outdoor employees, mean age 36.4±2.5 years). The Ocular Surface Disease Index questionnaire was used to assess ocular dryness. Tear film assessment was carried out using phenol red thread (PRT), tear film osmolarity test, and fluorescein tears breakup time (FTBUT) with slit-lamp biomicroscopy. Both indoor and outdoor employees showed mild-to-moderate ocular dryness. A significant difference (P=0.004) was found for the tear quality test (FTBUT) between the indoor (8.58±4.8) and outdoor (5.54±1.3) employees. However, no significant differences for the tear quantity tests (tear osmolarity and PRT) between the indoor and outdoor employees were observed. Dry eye cases were detected in both groups. This might be due to the hot dry environment in Riyadh and the use of air conditioners commonly used indoors. A significant difference was observed for the tear film stability, which might be due to the effect of environment and/or visual display unit use.


c-Met activation promotes extravasation of hepatocellular carcinoma cells into 3D-cultured hepatocyte cells in lab-on-a-chip device.
Activation of c-Met signaling is associated with an aggressive phenotype and poor prognosis in hepatocellular carcinoma (HCC); however, its contribution to organ preference in metastasis remains unclear. In this study, using a Lab on a Chip device, we defined the role of aberrant c-Met activation in regulating the extravasation and homing capacity of HCC cells. Our studies showed that (i) c-Met overexpression and activation direct HCC cells preferentially towards the hepatocytes-enriched microenvironment, and (ii) blockage of c-Met phosphorylation by a small molecule inhibitor attenuated extravasation and homing capacity of HCC cells. These results, thus, demonstrate the role of c-Met signaling in regulating the colonization of HCC cells preferentially in the liver.


Modulation of experimental osteoporosis in rats by the antioxidant beverage effective microorganism-X (EM-X).
Osteoporosis is a disease of aging associated with bone loss that often occurs without symptoms until microarchitectural deterioration becomes so significant that bone fracture occurs. The effective microorganism-X (EM-X) is an antioxidant beverage derived from ferment of unpolished rice, sea weeds and papaya with effective microorganisms of lactic acid bacteria, yeast and photosynthetic bacteria (containing minerals, alpha-tocopherol, lycopene, ubiquinone, saponin and flavonoids). The levels of serum estradiol (E(2)) and the bone density of the middle and epiphysis of femurs were assessed in order to determine the effect of EM-X on osteoporosis in ovariectomized rat (an animal model of postmenopausal osteoporosis). EM-X (1 ml/rat/day) was initially administrated by gavage to rats which were then allowed to consume 10% (v/v) EM-X in water freely for 3 months. There was no statistical significance of E(2) level between sham operation group and control group, indicating that sham operation did not affect E(2) level. However, the E(2) levels in the ovariectomized rats tended to increase after treatment of EM-X for 3 months. The bone density of the middle and epiphysis of femur in both sham operation and ovariectomy group decreased with time. Rats receiving EM-X for 3 months after sham operation or ovariectomy had increased bone density of the middle of femur that was statistically significant (P < 0.01 and P < 0.05). The bone density of the epiphysis of femur in both sham operation and ovariectomy group were significantly increased, an outcome highly suggestive of the beneficial effects of EM-X on bone density of the middle and the epiphysis of femur in the rats with or without ovariectomy.


An investigation into the factors affecting investigator-initiated trial start-up in Ireland.
In common with many countries, Ireland has seen an increasing trend in the number of clinical trials conducted over the past few years. Yet, as elsewhere, trialists in Ireland face several problems and barriers in the starting-up of clinical trials. These barriers impede trial activity significantly, with consequent impacts on patient care. It is critical to understand these issues, to develop approaches to facilitate trial start up. This study identifies the challenges in conducting clinical trials in Ireland and specifically the contractual, ethical, logistical, and regulatory barriers that hinder the start-up of investigator-led trials in Ireland. Data for this study were collected in two stages. In the first stage, a survey was conducted among trialists in Ireland. A total of 44 trialists responded to the survey, and information was collected about their experience in conducting clinical trials, the scale and nature of their most recently completed trial, and the details of specific barriers they encountered during the starting-up of the trial. In the second stage, nine semi-structured interviews were conducted with the awardees of 2018 Irish Health Research Board's Definitive Intervention Feasibility Award. These interviews facilitated a deeper exploration of issues and problems in conducting clinical trials in Ireland. This study identified several issues and bottlenecks in starting-up clinical trials in Ireland with contracts and ethical approval cited as the major issues. The data shows that site identification and activation was also problematic in some cases. Several respondents reported difficulties in accessing dedicated time for protocol development and believe that support in this area can be greatly beneficial. It was reported that availability of skilled staff members like statisticians and data managers was as an issue, especially for small trials. This study found that several factors impact trial initiation and progression in Ireland. Delays associated with obtaining contract and ethics approval are perceived as major barriers. Specialist supports in areas such as ethics and regulatory affairs and availability of specialised staff members in areas such as statistics and data management are key actions to enable enhanced clinical trial activity in Ireland.


Cohort study of THRIVE predicting adverse outcomes in acute ischemic stroke of the anterior circulation and posterior circulation after 3 months and 1 year of follow-up.
To evaluate the difference of Totaled Health Risks In Vascular Events (THRIVE) in predicting adverse outcomes in acute ischemic stroke (AIS) of the anterior circulation and posterior circulation at 3-month and 1-year follow-up. A total of 858 patients with AIS were followed up for 3 months and 1 year, and their data prospectively collected. The occurrence of death or moderate to severe disability (modified Rankin Scale ≥ 3 points) was regarded as the endpoint. MedCalc software was used to create the THRIVE receiver operating characteristic curve. The area under the curve (AUC) was calculated to compare the THRIVE scale in predicting adverse outcomes in AIS of the anterior and posterior circulation and compare the differences. At 3-month follow-up, the AUC of THRIVE was 0.685 (95% CI 0.644-0.724) for AIS of the anterior circulation and 0.709 (95% CI 0.647-0.765) for AIS of the posterior circulation. The area difference between them was 0.0235 (95% CI -0.0728-0.120, P = 0.6330[>0.05]). The AUC of THRIVE for AIS in the anterior circulation at 1 year was 0.701 (95% CI 0.660-0.740), and that for AIS in the posterior circulation at 1 year was 0.747 (95% CI 0.687-0.800). The area difference between them was 0.0458 (95% CI -0.0489-0.140, P = 0.3436 [>0.05]). The difference was not statistically significant. THRIVE can well predict the short-term and long-term adverse prognosis of AIS in the anterior and posterior circulation and has the same predictive effect.


A new species of the genus Arcoptilia Arenberger (Lepidoptera, Pterophoridae) from Angola.
The new species Arcoptilia naumanni sp. nov. (Lepidoptera, Pterophoridae) is described and illustrated from males found in Angola. Platyptilia rufamaculata Gielis, 2011, syn. nov. is established as a junior synonym of Arcoptilia pongola Ustjuzhanin & Kovtunovich, 2010.


Reconciling morphological and molecular classification of predatory ciliates: Evolutionary taxonomy of dileptids (Ciliophora, Litostomatea, Rhynchostomatia).
The order Dileptida is a small group of predatory ciliates characterized by a proboscis serving for prey capture. Although monophyly of the order is strongly supported, generic relationships between dileptid taxa were left mostly unresolved in 18S rRNA gene phylogenies. To overcome this problem, we applied the synergistic effect of combining multiple molecular markers with morphological data. Furthermore, we inferred dileptid evolutionary history by a multifaceted analysis strategy, including tree-building methods, phylogenetic networks, split spectrum analysis, quartet likelihood mapping, and reconstruction of ancestral morphologies. This complex approach revealed: (1) monophyly of the families Dimacrocaryonidae and Dileptidae; (2) polyphyly of Microdileptus, Pseudomonilicaryon, and Rimaleptus; and (3) homoplastic nature of several generic diagnostic features, viz., macronuclear pattern, size of oral bulge opening, and orientation of preoral kineties. Controversies in the internal phylogeny of the family Dimacrocaryonidae could be elucidated after reconstruction of ancestral morphologies at deeper nodes of phylogenetic trees in a combination with budding evolutionary processes. Moreover, we solved the "Rimaleptus" dilemma by splitting the family Dimacrocaryonidae into two new subfamilies, the Dimacrocaryoninae with two-rowed dorsal brush and the Rimaleptinae with multi-rowed brush as well as by establishing a new genus, Rurikoplites, from whose species several dimacrocaryonid genera very likely evolved by budding.