Synthesis, nucleic acid binding and cytotoxicity of polyethyleneimine-copper(II) complexes containing 1,10-phenanthroline and l-valine.
The polymer-copper(II) complex samples, [Cu(phen)(l-Val) BPEI]Cl·H(2)O, with varying degrees of coordination in the polymer chain, were prepared and characterized by elemental analysis and spectroscopic methods. The binding of these complex samples with both DNA and RNA has been investigated. The experimental results indicate that the polyethyleneimine-copper(II) complex samples bind with DNA and RNA mostly through surface binding; but hydrogen bonding and van der Waals interactions are also present. Evaluation of cytotoxic activity of a sample of polymer-copper(II) complex with higher degree of coordination against different cancer cell lines proved that the complex exhibited cytotoxic specificity and significant cancer cell inhibition rate.


Synthesis of Polysubstituted Furan Frameworks via [3 + 2] Annulation of N-Enoxyimides with Chelated Alkynes Initiated by Rh(III)-Catalyzed C-H Activation.
A variety of 2,3,5-trisubstituted furans were synthesized by virtue of a Rh(III)-catalyzed vinylic C-H coupling of N-enoxyimides with propargyl alcohols or amines. In this protocol, N-enoxyimides served as a one-oxygen and two-carbon synthon and the -OH/-NHR moiety in the alkynes was found to be crucial for realizing the desired chemo-/regioselectivity. Detailed experimental mechanistic studies together with DFT calculations clarified the sequential C-H activation/regioselective alkyne insertion/simultaneous O-N bond cleavage and hydrogen transfer/intramolecular nucleophilic addition/aromatization reaction path, which involved a distinctive Rh(V) carbene species as the active intermediate.


Redescription of Ceratothoa carinata (Bianconi, 1869) and Ceratothoa oxyrrhynchaena Koelbel, 1878 (Crustacea: Isopoda: Cymothoidae), buccal-attaching fish parasites new to Australia.
Ceratothoa carinata (Bianconi, 1869) and Ceratothoa oxyrrhynchaena Koelbel, 1878 are recorded for the first time from Australia and redescribed. Ceratothoa curvicauda Nunomura, 2006 is synonymised with Ceratothoa carinata. Brief accounts are given on the distribution and hosts of these species.


Corneal decompensation after laser in situ keratomileusis in fuchs' endothelial dystrophy.
To report corneal decompensation after laser in situ keratomileusis (LASIK) in a patient with Fuchs' endothelial dystrophy. Observational case report. A 47-year-old woman with cornea guttata without symptoms or findings of corneal edema had uneventful LASIK for -5.50 -0.50 x 150 in the right eye and -4.00 -1.25 x 170 in the left eye. Postoperatively, she developed corneal edema, with significant loss of best-corrected visual acuity in both eyes. Preoperative corneal thickness was 587 microm in the right eye and 549 microm in the left eye, measured by ultrasound pachymetry. These readings were 550 and 560 microm on day 67 postoperatively. Endothelial cell counts showed means of 1209 and 1661 cells/mm2 in the right and left eyes, respectively. Caution is suggested when considering LASIK in eyes with severe cornea guttata.


Effect of different blood groups on tympanometric findings and acoustic reflex thresholds.
The blood group can have an effect on the auditory system, and it is suggested that it could be an indicator of noise-induced hearing loss. There could be changes in the immittance findings, too, in adults having different blood groups. The present study attempted to determine if there are any differences in tympanometric results (admittance, peak pressure, gradient, resonance frequency, and ear canal volume) and acoustic reflex thresholds (ART) at 500, 1000, 2000 and 4000 Hz between individuals with different blood groups (A positive, B positive, O positive and AB positive). Eighty normal hearing adults between the age of 18 and 27 years were considered for the study. They were divided into 20 participants, each with blood groups A, B, AB, and O. The immittance findings were recorded from all the participants of the study. The results showed that the resonance frequency was slightly higher in blood group O compared to other blood groups. Also, the acoustic reflex thresholds were slightly elevated at all frequencies (ipsilateral and contralateral) for individuals with blood group O. The results of the study suggest possible reduced outer hair cells in persons with blood group O. This could have resulted in elevated acoustic reflex thresholds.


Comorbidity and insurance as predictors of disability after traumatic brain injury.
To examine the unique contribution of self-reported medical comorbidity and insurance type on disability after traumatic brain injury (TBI). Inception cohort design at 1-year follow up. A university affiliated rehabilitation hospital. Adults with mild-complicated to severe TBI (N=70). Not applicable. Self-reported medical comorbidities were measured using the Modified Cumulative Illness Rating Scale, while insurance type was classified as commercial or government-funded; disability was measured using the Disability Rating Scale. Two models were run using multiple linear regression, and the best-fitting model was selected on the basis of Bayesian information criterion. The full model, which included self-reported medical comorbidity and insurance type, was significantly better fitting than the reduced model. Participants with a longer duration of posttraumatic amnesia, more self-reported medical comorbidities, and government insurance were more likely to have higher levels of disability. Meanwhile, individual organ systems were not predictive of disability. The cumulative effect of self-reported medical comorbidities and type of insurance coverage predict disability above and beyond well-known prognostic variables. Early assessment of medical complications and improving services provided by government-funded insurance may enhance quality of life and reduce long-term health care costs.


Integration of Lean Visual Management Tools Into Quality Improvement Practices in the Hospital Setting.
Lean management tools have proven effective in achieving high reliability in health care. Unstructured leader rounds, decentralized prevention bundle repositories, and unfavorable patient experience outcomes prompted leaders on a thoracic and cardiovascular surgery unit to find other methods to address these issues and positively impact outcomes. Nurse sensitive indicator prevention bundles, root cause analysis tools, and best practices were used to develop Kamishibai Cards (K-Cards) for each measure targeted. K-Cards were implemented to standardize processes, engage patients in their care, and promote staff identification of barriers and solutions. Nurse-sensitive indicators and patient experience metrics were positively impacted by Kamishibai Rounding. K-Cards promote a state of continuous improvement, which supports sustainability of evidence-based practice and best practices that were implemented. K-Cards use high-reliability principles to standardize nursing practice to promote quality outcomes.


The determination of protein phosphorylation on electrophoresis gel blots by laser ablation inductively coupled plasma-mass spectrometry.
Laser ablation interfaced with inductively coupled plasma-mass spectrometry is described as a new method to determine the presence of phosphorylated proteins on electrophoresis gel blots. The method was applied to the phosphoprotein beta-casein with good detection levels being observed at 16 pmole. Attempts at using the technique to detect beta-casein on electrophoresis gels are also described.


Clinical comparison of the visual parameters in infants with intrauterine growth retardation vs. infants with normal birth weight.
We measured vision function in a number of 7-month-old infants with intrauterine growth retardation (IUGR) and compared these findings to those for 7-month-old infants of normal birth weight. The IUGR infants had an average visual acuity of 6/162 (20/540) and an average spherical refractive error of 1.49 D hyperopia. The normal birth weight infants had an average visual acuity of 6/118.8 (20/396) and an average spherical refractive error of 0.94 D hyperopia. However, the differences between the infant groups for visual acuity and refractive error were not statistically significant. Anisometropia, astigmatism, and strabismus were infrequent for both infant groups. The results of this study suggest that IUGR infants have visual abilities resembling those of normal birth weight infants.


Real-world outcomes of patients with renal cell carcinoma, surgically treated at regional hospitals, based on a prospective long-term survey of the pre-robotic era.
Renal cancer surgery is frequently performed in small regional hospitals in Japan. This study evaluated the outcomes of renal cancer surgery, comparing results from the pre-robotic surgery era with those obtained with robotic surgery. This prospective cohort study was conducted on patients who underwent renal cancer surgery between 2008 and 2013 at 14 hospitals, comprising 13 regional hospitals and a university hospital, registered in the Tohoku Urological Evidence-Based Medicine Study Group. The patients' backgrounds; perioperative data; annual postoperative renal function; and prognostic surveys, performed over a median follow-up period of 10 years were obtained. In 930 surgical cases at the 14 registered hospitals, the 10-year recurrence-free survival rates of cT1a, cT1b, cT2, and cT3 were 0.9326, 0.8501, 0.5786, and 0.5101, respectively. Meanwhile, the 10-year overall survival rates were 0.9612, 0.8662, 0.7505, and 0.7209, respectively. Long-term observation in patients with cT1 showed that vessel involvement and high tumor grade were prognostic factors for recurrence. As a noteworthy fact, radical nephrectomy was performed in 53.3% of patients with cT1a at the regional hospitals. However, even in patients with preoperative chronic kidney disease stage 3, radical nephrectomy was not a prognostic factor of renal function. This indicates that compensatory mechanisms had been working for a long time in many patients who underwent radical nephrectomies without hypertension and preoperative proteinuria, which were predictors of end-stage renal disease. Based on a prospective long-term survey of the pre-robotic era, our results suggested no difference of the survival outcomes between the university hospital and regional hospitals. Our study provides baseline data to evaluate the outcomes of renal cancer robotic surgery, performed at regional hospitals.


Electron modulated arc therapy (EMAT) using photon MLC for postmastectomy chest wall treatment I: Monte Carlo-based dosimetric characterizations.
To study the dosimetric properties of electron arc beams delivered by photon-beam multi-leaf collimators (pMLC) in electron modulated arc therapy (EMAT) for postmastectomy chest wall treatments. Using the Monte Carlo method, we simulated a 2100EX Varian linear accelerator and verified the beam models in a water tank. Dosimetric characterizations were performed on cylindrical water phantoms of elliptical bases with various field sizes, arc ranges and source-to-surface distances (SSDs) for 6, 9 and 12 MeV beam energy. The arc beam has a higher bremsstrahlung dose than the static beam at the isocenter due to crossfire, but choosing a field size greater than 5 cm effectively reduces the bremsstrahlung dose. The depths of the 90% maximum dose located at 1.7, 2.8 and 4.1 cm for 6, 9 and 12 MeV, respectively, are similar to those of the static beams and independent of the field size and arc range. Based on the study, we recommend using the 5 cm field width for electron arc beams considering both bremsstrahlung dose at the isocenter and the arc profile penumbra. To ensure sufficient PTV edge coverage, we recommend a field length extension of at least 4 cm from PTV's edge for all beam energies and an arc extension of around 7°, 5°, and 5° for beam energies 6, 9, and 12 MeV, respectively. These dosimetric characterizations are the basis of pMLC-delivered EMAT treatment planning for postmastectomy chest wall patients.


Radical promoted Wagner-Meerwein-type rearrangement of epoxides in camphoric systems using a Ti(III) radical source.
[Chemical reaction: see text] A radical based Wagner-Meerwein-type rearrangement has been observed in camphoric systems. The radical was generated from the epoxide using Cp2TiCl as the radical source. The radical initiator Cp2TiCl was prepared in situ from commercially available Cp2TiCl2 and Zn dust in THF under argon.


Sustained and intensified lacustrine methane cycling during Early Permian climate warming.
Lakes are a major emitter of the atmospheric greenhouse gas methane (CH4); however, their roles in past climate warming episodes remain poorly understood owing to a scarcity of geological records. Here we report the occurrence of sustained and intensified microbial CH4 cycling in paleo-Lake Junggar in northwestern China, one of the largest known Phanerozoic lakes, during Early Permian climate warming. High-precision U-Pb geochronology refines the age of the upper Lucaogou Formation to the Artinskian, which marks a major glacial-to-postglacial climate transition. The 13C-enriched authigenic dolomites indicate active methanogenesis in the anoxic lake sediments, and 13C-depleted hopanes suggest vigorous methanotrophy in the water column. The intensification of CH4 cycling coincided with increasing global temperature, as evidenced from elevated continental chemical weathering. Our results suggest that the lacustrine CH4 emissions acted as a positive feedback to global warming and contributed to the demise of the Late Paleozoic Ice Age.


Bleeding patterns and acceptability among Norplant users in two Asian countries.
Changes in menstrual bleeding patterns are the most frequent reason for discontinuing NORPLANT during the first year of use. Although NORPLANT is used by more women in Asia than in any other region, the changes that occur among these women are not well documented. In pre-introductory clinical trials of NORPLANT in the Philippines and Sri Lanka, 175 women were enrolled with greater than 95% continuing the method after one year. Daily menstrual bleeding calendars were kept by 94% of subjects for nine months and by 66% for one year. In contrast to findings in previous studies which showed that approximately 60% of NORPLANT users had bleeding disruptions in the first year of use, almost all of these women experienced bleeding disruptions. In a one-year study of menstrual pattern changes, increased bleeding was found to occur with the same frequency as reduced bleeding. However, the changes experienced by the Asian women tended to be decreases, rather than increases, in menstrual bleeding.


Syndecan-1 and -4 differentially regulate oncogenic K-ras dependent cell invasion into collagen through α2β1 integrin and MT1-MMP.
Syndecans function as co-receptors for integrins on different matrixes. Recently, syndecan-1 has been shown to be important for α2β1 integrin-mediated adhesion to collagen in tumor cells by regulating cell adhesion and migration on two-dimensional collagen. However, the function of syndecans in supporting α2β1 integrin interactions with three-dimensional (3D) collagen is less well studied. Using loss-of-function and overexpression experiments we show that in 3D collagen syndecan-4 supports α2β1-mediated collagen matrix contraction. Cell invasion through type I collagen containing 3D extracellular matrix (ECM) is driven by α2β1 integrin and membrane type-1 matrix metalloproteinase (MT1-MMP). Here we show that mutational activation of K-ras correlates with increased expression of α2β1 integrin, MT1-MMP, syndecan-1, and syndecan-4. While K-ras-induced α2β1 integrin and MT1-MMP are positive regulators of invasion, silencing and overexpression of syndecans demonstrate that these proteins inhibit cell invasion into collagen. Taken together, these data demonstrate the existence of a complex interplay between integrin α2β1, MT1-MMP, and syndecans in the invasion of K-ras mutant cells in 3D collagen that may represent a mechanism by which tumor cells become more invasive and metastatic.


Heat-shock inducible polyubiquitin gene UbI undergoes alternative initiation and alternative splicing in mature chicken testes.
Ubiquitin, a heat-shock protein highly expressed during spermatogenesis, plays an essential role in the differentiation of the germinal cells, particularly in the structural changes of chromatin taking place at the end of the process. To shed light on the mechanisms that modulate transcriptional activity of the heat-shock inducible polyubiquitin gene UbI during spermatogenesis and stabilize the message when transcription is not longer active, we have compared the characteristics of UbI transcripts in mature and immature testes and somatic cells. In mature chicken testes, transcription starts at a site placed closer to the heat-shock promoters than in somatic tissues. This site is upstream from the TATA box used in somatic cells. In addition, UbI transcript undergoes an alternative splicing that produces a longer 5' untranslated region in mature testis. These findings may provide a basis for the observed increase in expression of UbI in mature chicken testes and for the stability of the message when transcription ceases at the end of spermatogenesis.


Effects of long-term, high-dose bovine thyrotropin administration on human thyroid tissues from patients with graves' disease and normal subjects xenografted into nude mice.
We have attempted to determine whether the administration of thyrotropin would have any different functional or histological effects on Graves' tissue as opposed to human normal thyroid tissue in an in vivo situation (i.e., after xenograft into nude athymic mice). A dosage of 0.03 units per mouse of bovine thyroid-stimulating hormone (b-TSH) was injected intraperitoneally daily for 6 consecutive weeks into xenografted mice. The parameters measured included the free T4 index and thyroid autoantibodies during the course of b-TSH injections. Tritiated (3H)-thymidine incorporation into thyroid epithelial cells (TECs) and TEC HLA-DR expression were measured in the thyroid tissue at the time of human surgery and at sacrifice; in addition, light-microscopical observations were made at those times. Although there was a decline in free T4 index values during the course of the study, there was light-microscopical evidence suggestive of hyperplasia in both types of xenografted thyroid tissue. The TSH appeared to result in thyrocyte down-regulation, possibly of receptor or postreceptor origin. The administration of the b-TSH seemed to induce TEC HLA-DR expression in this study. Because these results differ from the effects of TSH on TEC in vitro with respect to TEC HLA-DR expression, it may be postulated that there are other factors liberated in vivo in the nude mice that interact with the TEC and TSH and initiate the TEC HLA-DR expression. We conclude that there are no significant differences between the responses of Graves' tissue and the normal human thyroid tissue in these studies.


Correction: Transcript Analysis and Regulative Events during Flower Development in Olive (Olea europaea L.).
[This corrects the article DOI: 10.1371/journal.pone.0152943.].


In vitro antileishmanial activity and cytotoxicity of essential oil from Lippia sidoides Cham.
Leishmaniasis is a widespread tropical infection caused by different species of Leishmania protozoa. There is no vaccine available for Leishmania infections and conventional treatments are very toxic to the patients. Therefore, antileishmanial drugs are urgently needed. In this study we have analyzed the effects of essential oils from Lippia sidoides (LSEO) and its major compound thymol on the growth, viability and ultrastructure of Leishmania amazonensis. The essential oil and thymol showed significant activity against promastigote forms of L. amazonensis, with IC(50)/48 h of 44.38 and 19.47 μg/mL respectively. However, thymol showed toxicity against peritoneal macrophages and low selectivity against the promastigotes when compared with the crude LSEO. On the other hand, no cytotoxic effect was observed in macrophages treated with the crude essential oil. Incubation of L. amazonensis-infected macrophages with LSEO showed a marked reduction in amastigote survival within the macrophages. Significant morphological alterations as accumulation of large lipid droplets in the cytoplasm, disrupted membrane and wrinkled cells were usually seen in treated parasites. The LSEO's activity against both promastigote and the amstigote forms of L. amazonensis, together with its low toxicity to mammalian cells, point to LSEO as a promising agent for the treatment of cutaneous leishmaniasis.


A new method for resolution of two- and three-component mixtures of fluorophores by phase-sensitive detection of fluorescence.
We describe a new method for the analysis of phase-sensitive fluorescence emission spectra. This method permits the resolution of three-component mixtures using spectra measured at a single modulation frequency. Phase-sensitive spectra are recorded using one modulation frequency, at a number of arbitrary detector phase angles. It is not necessary to suppress any one component. The spectra are then used to estimate the component lifetimes and steady-state fractional intensities using a nonlinear least-squares analysis procedure. The only requirement for the analysis is the knowledge of the steady-state spectra of the individual components. This procedure allowed the resolution of a two-component mixture of 9-methylanthracene (4.5 ns) and 9,10-diphenylanthracene (5.9 ns). It should be noted that resolution of two lifetimes which differ by only 30% is a difficult task. Additionally, we resolved a three-component mixture with lifetimes that differed fourfold: p-bis[2-(5-phenyloxazolyl)]benzene (1.3 ns), 9-methylanthracene (4.5 ns), and 9,10-diphenylanthracene (5.9 ns). Conveniently, the technique utilizes a commercially available fixed-frequency phase fluorometer.


Effects of PTH on osteocyte function.
Osteocytes are ideally positioned to detect and respond to mechanical and hormonal stimuli and to coordinate the function of osteoblasts and osteoclasts. However, evidence supporting the involvement of osteocytes in specific aspects of skeletal biology has been limited mainly due to the lack of suitable experimental approaches. Few crucial advances in the field in the past several years have markedly increased our understanding of the function of osteocytes. The development of osteocytic cell lines initiated a plethora of in vitro studies that have provided insights into the unique biology of osteocytes and continue to generate novel hypotheses. Genetic approaches using promoter fragments that direct gene expression to osteocytes allowed the generation of mice with gain or loss of function of particular genes revealing their role in osteocyte function. Furthermore, evidence that Sost/sclerostin is expressed primarily in osteocytes and inhibits bone formation by osteoblasts, fueled research attempting to identify regulators of this gene as well as other osteocyte products that impact the function of osteoblasts and osteoclasts. The discovery that parathyroid hormone (PTH), a central regulator of bone homeostasis, inhibits sclerostin expression generated a cascade of studies that revealed that osteocytes are crucial target cells of the actions of PTH. This review highlights these investigations and discusses their significance for advancing our understanding of the mechanisms by which osteocytes regulate bone homeostasis and for developing therapies for bone diseases targeting osteocytes.


[Long-term follow up of children with transposition of great vessels with intact interventricular septum].
From January 1971 to January 1988, 140 patients were diagnosed of complete transposition of the great arteries with an intact ventricular septum. These patients are the 6% of the 2,322 children diagnosed of congenital heart disease by catheterization and angiography in this 17 year period. The overall mortality was 63.5%. Sixty children died at a mean age of 55 days before cardiac surgery was performed, mostly before 1982. Forty nine patients underwent a Senning procedure with a surgical mortality of 30.6%. Between 1983 and 1988, with the use of infusion of prostaglandin E in the neonatal period, 28 children underwent a Senning procedure at a mean age of 12 months with a surgical mortality of 17.8%, and an actuarial survival rate of 80.9%. At late examination the 55.8% of the survivors were asymptomatic and the 8.8% showed caval or pulmonary venous obstruction.


[Transport of large organic ions through syringomycin channels in the membranes containing dipole modifiers].
The effect of the membrane dipole potential (Phid) on a conductance and a steady-state number of functioning channels formed by cyclic lipodepsipeptide syringomycin E (SRE) in bilayer lipid membranes made from phosphocholine and bathed in 0.4 M solution of sodium salts of aspartate, gluconate and chloride was shown. The magnitude of Phid was varied with the introduction to membrane bathing solutions of phloretin, which reduces the Phid, and RH 421, increasing the Phid. It was established that in all studied systems the increase in the membrane dipole potential cause a decrease in the steady-state number of open channels. In the systems containing sodium salts of aspartate (Asp) or gluconate (Glc), changes in the number of functioning channels are in an order of magnitude smaller than in systems containing sodium chloride. At the same time, the conductance (g) of single SRE-channels on the membranes bathed in NaCI solution increases with the increase in Phid, and in the systems containing NaAsp or NaGlc the conductance of single channels does not depend on the Phid. The latter is due to the lack of cation/anion selectivity of the SRE-channels in these systems. The different channel-forming activity of SRE in the experimental systems is defined by the gating charge of the channel and the partition coefficient of the dipole modifiers between the lipid and aqueous phases.


The widespread presence of triazole fungicides in greenhouse soils in Shandong Province, China: A systematic study on human health and ecological risk assessments.
Triazole fungicides (TFs) are extensively used on greenhouse vegetables and are ubiquitously detected in the environment. However, the human health and ecological risks associated with the presence of TFs in the soil are unclear. In this study, ten widely used TFs were measured in 283 soil samples from vegetable greenhouses across Shandong Province, China, and their potential human health and ecological risks were assessed. Among all soil samples, difenoconazole, myclobutanil, triadimenol, and tebuconazole were the top detected TFs, with detection rates of 85.2-100%; these TFs had higher residues, with average concentrations of 5.47-23.8 μg/kg. Although most of the detectable TFs were present in low amounts, 99.3% of the samples were contaminated with 2-10 TFs. Human health risk assessment based on hazard quotient (HQ) and hazard index (HI) values indicated that TFs posed negligible non-cancer risks for both adults and children (HQ range, 5.33 × 10-10 to 2.38 × 10-5; HI range, 1.95 × 10-9 to 3.05 × 10-5, <1). Ecological risk assessment based on the toxicity exposure ratio (TER) and risk quotient (RQ) values indicated that difenoconazole was a potential risk factor for soil organisms (TERmax = 1 for Eisenia foetida, <5; RQmean = 1.19 and RQmax = 9.04, >1). Moreover, 84 of the 283 sites showed a high risk (RQsite range, 1.09-9.08, >1), and difenoconazole was the primary contributor to the overall risk. Considering their ubiquity and potential hazards, TFs should be continuously assessed and prioritized for pesticide risk management.


Mental health parity: a review of research and a bibliography.
This article summarizes the content of a meeting held in July 2001 to (1) review what is known about the effect of parity based on research already done, (2) identify what is likely to be known from research in progress, and (3) identify the knowledge gaps that still exist. An annotated bibliography of studies and reports on parity from 1996 through 2001 is included.


Two cases of dorsal defect of the patella with arthroscopically visible cartilage surface perforations.
Dorsal defect of the patella is an approximately 1-cm, circular, radiolucent, well-marginated benign lesion invariably located in the superlateral aspect of the patella. Only approximately 50 cases have been described in the world literature, of which < 10 cases have been studied histologically. We report two patients with bilateral, virtually symmetrical, dorsal defects of the patella and describe the arthroscopic and histologic findings. Case 1 was a 14-year-old girl and case 2 was a 35-year-old man. Cartilage perforations were seen via arthroscopy on the cartilage surface of both knees. The pathophysiology of this disorder remains to be clarified, although van Holsbeeck et al. proposed that vastus lateralis traction injury in the ossification process of the patella may be involved, as in the case of bipartite patella. The present arthroscopic and histological findings support this hypothesis.


Auditory attention to frequency and time: an analogy to visual local-global stimuli.
Two priming experiments demonstrated exogenous attentional persistence to the fundamental auditory dimensions of frequency (Experiment 1) and time (Experiment 2). In a divided-attention task, participants responded to an independent dimension, the identification of three-tone sequence patterns, for both prime and probe stimuli. The stimuli were specifically designed to parallel the local-global hierarchical letter stimuli of [Navon D. (1977). Forest before trees: The precedence of global features in visual perception. Cognitive Psychology, 9, 353-383] and the task was designed to parallel subsequent work in visual attention using Navon stimuli [Robertson, L. C. (1996). Attentional persistence for features of hierarchical patterns. Journal of Experimental Psychology: General, 125, 227-249; Ward, L. M. (1982). Determinants of attention to local and global features of visual forms. Journal of Experimental Psychology: Human Perception and Performance, 8, 562-581]. The results are discussed in terms of previous work in auditory attention and previous approaches to auditory local-global processing.


An immunoglobulin G capture assay (GACRIA) for anti-HTLV III/LAV and its use as a confirmatory test.
An immunoglobulin G (IgG) antibody capture assay (GACRIA) methodologically distinct from other assays for the detection of antibodies to human T-lymphotropic virus type III/lymphadenopathy-associated virus (anti-HTLV III/LAV) was developed and used to test 1,055 serum samples previously screened by a competitive assay (COMPRIA). Eight hundred and twenty-three (78%) sera were positive and 129 (12.2%) negative in both assays. The coefficient of correlation between the two assays was 0.87, and COMPRIA appeared more sensitive than GACRIA. On retesting 103 sera that gave initially conflicting results, 81 discrepancies were resolved, 77 because of a change in the COMPRIA result. The 22 persistently discrepant samples gave an equivocal or positive result by COMPRIA and were negative by GACRIA. Thirteen of these 22 were positive in a commercial ELISA (ELAVIA). Twenty of them were also tested by Western blot; all were reactive with at least two HTLV III/LAV protein bands. The persistently discrepant samples were of four types: laboratory control sera (n = 2); naturally occurring weakly reactive samples (n = 5); samples that were anti-HTLV III/LAV IgG negative but IgM positive (n = 5; all five individuals from whom these samples were drawn were symptomatic); samples from one laboratory that were probably accidentally contaminated with anti-HTLV III/LAV-positive serum (n = 10). It was concluded that GACRIA for anti-HTLV III/LAV is specific and adequately sensitive and, in conjunction with other assays, is a useful confirmatory test whose format could readily be changed to ELISA.


Epigenetic and genetic alterations and their influence on gene regulation in chronic lymphocytic leukemia.
To understand the changes of gene regulation in carcinogenesis, we explored signals of DNA methylation - a stable epigenetic mark of gene regulatory elements - and designed a computational model to profile loss and gain of regulatory elements (REs) during carcinogenesis. We also utilized sequencing data to analyze the allele frequency of single nucleotide polymorphisms (SNPs) and detected the cancer-associated SNPs, i.e., the SNPs displaying the significant allele frequency difference between cancer and normal samples. After applying this model to chronic lymphocytic leukemia (CLL) data, we identified REs differentially activated (dREs) between normal and CLL cells, consisting of 6,802 dREs gained and 4,606 dREs lost in CLL. The identified regulatory perturbations coincide with changes in the expression of target genes. In particular, the genes encoding DNA methyltransferases harbor multiple lost-in-cancer dREs and zero gained-in-cancer dREs, indicating that the damaged regulation of these genes might be one of the key causes of tumor formation. dREs display a significantly elevated density of the genome-wide association study (GWAS) SNPs associated with CLL and CLL-related traits. We observed that most of dRE GWAS SNPs associated with CLL and CLL-related traits (83%) display a significant haplotype association among the identified cancer-associated alleles and the risk alleles that have been reported in GWAS. Also dREs are enriched for the binding sites of the well-established B-cell and CLL transcription factors (TFs) NF-kB, AP2, P53, E2F1, PAX5, and SP1. We also identified CLL-associated SNPs and demonstrated that the mutations at these SNPs change the binding sites of key TFs much more frequently than expected. Through exploring sequencing data measuring DNA methylation, we identified the epigenetic alterations (more specifically, DNA methylation) and genetic mutations along non-coding genomic regions CLL, and demonstrated that these changes play a critical role in carcinogenesis through damaging the regulation of key genes and alternating the binding of key TFs in B and CLL cells.


SK2 channels regulate mitochondrial respiration and mitochondrial Ca2+ uptake.
Mitochondrial calcium ([Ca2+]m) overload and changes in mitochondrial metabolism are key players in neuronal death. Small conductance calcium-activated potassium (SK) channels provide protection in different paradigms of neuronal cell death. Recently, SK channels were identified at the inner mitochondrial membrane, however, their particular role in the observed neuroprotection remains unclear. Here, we show a potential neuroprotective mechanism that involves attenuation of [Ca2+]m uptake upon SK channel activation as detected by time lapse mitochondrial Ca2+ measurements with the Ca2+-binding mitochondria-targeted aequorin and FRET-based [Ca2+]m probes. High-resolution respirometry revealed a reduction in mitochondrial respiration and complex I activity upon pharmacological activation and overexpression of mitochondrial SK2 channels resulting in reduced mitochondrial ROS formation. Overexpression of mitochondria-targeted SK2 channels enhanced mitochondrial resilience against neuronal death, and this effect was inhibited by overexpression of a mitochondria-targeted dominant-negative SK2 channel. These findings suggest that SK channels provide neuroprotection by reducing [Ca2+]m uptake and mitochondrial respiration in conditions, where sustained mitochondrial damage determines progressive neuronal death.


Phosphorus supply level is more important than wheat variety in safe utilization of cadmium-contaminated calcareous soil.
Screening and cultivating crop varieties with low Cd accumulation is an effective way to safely utilize the Cd slightly contaminated soil. The characteristics and mechanism of Cd uptake by 13 wheat varieties in two calcareous soils with similar Cd contamination level but different P supply level were studied. The grain Cd concentration of almost all varieties in low-P soil was significantly higher than that in high-P soil and exceeded the maximum level of 0.2 mg kg-1 recommended by the Codex Alimentarius Commission. The pH value of low-P soil was significantly lower than that of high-P soil by 0.27 units, while leaf [Mn] (proxy for rhizosphere carboxylates) and the activities of soil alkaline phosphatase and phytase were significantly higher than those of high-P soil by 35%, 55%, and 286%, respectively. The exchangeable Cd concentration in low-P soil was 2.93 times higher than that in high-P soil, while the Cd concentration of oxides and organic species was significantly lower than that in high-P soil by 21% and 64%, respectively, collectively increasing soluble Cd concentration in low-P soil by 38%. In low-P calcareous soil, P mobilization induced the change of root-zone microenvironment, resulting in the mobilization of Cd.


Fear of COVID-19 and Preventive Health Behavior: Mediating Role of Post-Traumatic Stress Symptomology and Psychological Distress.
The COVID-19 pandemic has been implicated in several mental health challenges faced by many people. These challenges can also arise due to the fear of being infected with COVID-19 and engaging in preventative behavior. This study investigated the mediating role of post-traumatic stress symptomology and psychological distress in the relationship between fear of COVID-19 and preventive health behavior. A sample of 1172 individuals (mean age = 22.9 years, 54.5% females) participated in the online survey. Correlation analysis revealed that preventive health behavior has a positive relationship with fear of COVID-19 and post-traumatic stress symptomology but a negative relationship with psychological distress. Further analysis indicated that post-traumatic stress symptomology and psychological distress mediated the relationship between fear of COVID-19 and preventive health behavior. Post-traumatic stress symptomology caused by the fear of COVID-19 could contribute to improving preventive health behavior while psychological distress caused by the fear of COVID-19 tends to hinder preventive health behavior. It is recommended that public and private agencies should assist in promoting COVID-19 targeted education. Attention should also be focused on people's mental health status as means of preventing COVID-19.


Novel Definition of Stroke "Good Responders" Predicts 90-Day Outcome after Thrombolysis.
Identifying predictors of good response in thrombolytic-treated stroke is important to clinical care, resource allocation, and research design. We developed a simple, novel measure of "Good Responders" to assess if 2 short-term variables could predict 90-day outcomes after thrombolysis in stroke. Intravenous thrombolysis-treated stroke cases from June 2004 to June 2018 were analyzed from a stroke registry. Intraarterial treatment cases were excluded. Good responders (GR++) were defined as those with length of stay less than or equal to 3 days and discharge to home. Poor responders (GR- -) had length of stay more than 3 days and discharge other than home. Mixed responders (GR+/-) composed the remainder. Baseline characteristics and predictors of 90-day outcome were assessed. Of 261 patients, there were 101(38.7%) GR++, 67(25.7%) GR- -, and 93(35.6%) GR+/-. For GR++ versus GR- - versus GR+/-, there were differences in mean age (62.7, 71.2, 69.2; P = .0016), and baseline modified Rankin score (mRS) 0-2 (%: 94.9, 74.6, 84.8; P = .008). Younger age, male sex, lower values for systolic BP, glucose, and baseline mRS were associated with good responders. Older age, atrial fibrillation, symptomatic intracerebral hemorrhage, and baseline mRS greater than 2 were associated with poor responders. At 90 days, mortality was reduced in GR++ versus GR- - versus GR+/- (%alive: 92.6, 72, 86; P = .04), and mRS(0-2) (%: 36.8, 0, 11.8; P < .001). Good responders to thrombolysis are younger and have better baseline functional status. Our novel definition of "Good Responders", using 2 early variables of home disposition and short length of stay, may help predict 90-day post-thrombolytic outcome. Future work should focus on validating this definition.


Fabrication of a fluorescence probe via molecularly imprinted polymers on carbazole-based covalent organic frameworks for optosensing of ethyl carbamate in fermented alcoholic beverages.
Ethyl carbamate (EC), which is a group 2A carcinogen, is a byproduct formed in the alcohol fermentation process that can accumulate with heating, transportation, and storage. In this study, molecularly imprinted polymers (MIPs) on carbazole-based covalent organic frameworks (COFs) were prepared as a fluorescence probe for the optosensing of EC in fermented alcoholic beverages. The excellent optical properties of carbazole-based COFs coupled with the good adsorption and selectivity of MIPs provided fast and efficient recognition of EC. MIPs on carbazole-based COFs exhibited advantages of high efficiency, a good separation effect, fluorescence dependence, and reproducibility. A good linear relationship was obtained over the concentration range of 1-200 μg L-1, with a low limit of detection (LOD) of 0.607 μg L-1. The RSD precision and five-cycle reproducibility were lower than 4.91% and 6.38%, respectively, and the recoveries were 85.30%-109.49%. This optosensor was applied to quantify EC contents in several fermented alcoholic beverages, all of which were less than LOD. The results of the optosensors based on MIPs on carbazole-based COFs were then validated using standard gas chromatography-mass spectrometry (GC-MS), which gave results consistent with the proposed method.


Induction of mating behavior by apomorphine in sexually sated rats.
We have tested the hypothesis, suggested by our previous neurochemical studies, that the inhibition of sexual behavior that follows unrestricted mating could be caused by a blockade of dopaminergic transmission. Male rats were allowed to copulate until they reached a satiety criterion. The following day, after verification that they were sexually inactive, the animals were injected with the dopamine agonist, apomorphine, at doses of 80, 200, and 500 micrograms/kg body weight and their behavior with receptive females was recorded. A bell-shaped dose-response curve was found, with the 200 micrograms/kg dose having the maximal stimulatory effects on mating. Whereas these findings seem to support the above hypothesis, it should be noted that apomorphine treatments were unable to restore fully the copulatory pattern shown by sexually rested animals. This could be due to several factors including the interference of apomorphine-induced stereotypies, and/or the involvement of additional transmitter systems in the mechanisms of sexual satiety.


Timing the window of implantation by nucleolar channel system prevalence matches the accuracy of the endometrial receptivity array.
To test if nucleolar channel system (NCS) prevalence matches the accuracy of the endometrial receptivity array (ERA) for identification of the window of endometrial receptivity. Comparative retrospective study, May 2008-May 2012. University-affiliated infertility clinic. Forty-nine healthy oocyte donors, regularly cycling, aged 20-34 years with a body mass index of 19-25 kg/m2. Endometrial biopsies were collected throughout the menstrual cycle. All samples underwent transcriptomic signature identification by ERA testing (performed in a prior study) and quantification of NCS prevalence by using indirect immunofluorescence (performed in the present study). Concordance of ERA results determining the window of implantation with NCS prevalence was statistically analyzed using the kappa index. Based on dating according to the luteinizing hormone surge, specimens were dichotomized into receptive (n=24) and nonreceptive (n=25). The NCS prevalence was expressed as percentage of NCSs per endometrial epithelial cells in each endometrial biopsy. Concordance of ERA and NCS dating vs. luteinizing hormone yielded comparable kappa indices of 0.878 and 0.836, respectively. Direct comparison of ERA and NCS dating resulted in a kappa index of 0.796. Prevalence of NCS identifies the window of endometrial receptivity previously identified by their transcriptomic signature using the ERA.


Bone disease, hypophosphatemia and hyperparathyroidism after renal transplantation.
Long-term survivors after renal transplantation (RT) show: 1) decreased s-phosphorus 2) increased s-PTH 3) no correlation between s-PTH and s-phosphorus 4) increased amount of non-mineralized bone (osteomalacia), inversely correlated to s-phosphorus 5) decreased amount of trabecular bone (osteopenia) in RT patients with aseptic necorsis of bone. aseptic necrosis of bone after RT is mainly due to osteoid-induced osteopenia, perhaps aggravated by hypophosphatemic osteomalacia.


Modeling Challenges in Cost-Effectiveness Analysis of First-Line Immuno-Oncology Therapies in Non-small Cell Lung Cancer: A Systematic Literature Review.
The introduction of immuno-oncology (IO) therapies has changed the treatment landscape of non-small cell lung cancer (NSCLC). Numerous cost-effectiveness analyses (CEAs) and technology appraisals (TAs) evaluating IO therapies have been recently published. We reviewed economic models of first-line (1L) IO therapies for previously untreated advanced or metastatic NSCLC to identify methodological challenges associated with modeling cost effectiveness from published literature and TAs and to make recommendations for future CEAs in this disease area. A systematic literature review was conducted following Cochrane and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We searched MEDLINE, Embase, EconLit (January 2009-January 2020), and select conferences (since 2016) for CEAs of 1L IO treatments in patients with recurrent or metastatic, epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) mutation-negative NSCLC, published in English. TAs from England, Scotland, Canada, Australia, Germany, and France were also examined. Two reviewers screened the results and extracted the data. The quality of the CEAs was described using the Drummond checklist. In total, 46 records reporting on 38 unique models met protocol-defined criteria and were included. Five models adjusted for treatment switching or crossover in base-case analyses, and the remainder considered treatment switching or crossover to represent clinical practice and made no adjustment. Seven models used external real-world data for survival modeling or extrapolation validation. Six models that assumed long-term treatment benefit stopped at 3 or 5 years after initiation. Seven models used the observed time-on-treatment distribution from the trial, and eight used progression-free survival for treatment duration. All models compared one or more IO monotherapies or combination therapies with chemotherapy. Only one study directly compared different IO agents but did not consider the concordance issue across programmed death-ligand 1 (PD-L1) testing methods. Utilities were modeled by health state in 12 models, four applied a time-to-death approach, and ten explored both. None applied cure models. Variations in methodological challenges were seen across studies. Previous models took approaches that were followed in subsequent models, such as a 2-year stopping rule of IO duration or treatment-effect waning. Challenges such as heterogeneity in PD-L1 testing and survival extrapolation and validation using real-world data should be further considered for future models in advanced or metastatic NSCLC.


Patients' perspective about speech, swallowing and hearing status post-SARS-CoV-2 (COVID-19) recovery: E-survey.
The present study investigates the COVID-19 survivors' perspective on speech, swallowing, and hearing-related issues post-COVID-19. We further investigate the recovery duration for speech, swallowing, and hearing-related symptoms post-COVID. Survey study; E-survey. A total of 78 subjects (35.78 years ± 11.93) participated in the survey. All the participants were diagnosed with the RTPCR method. To understand the recovery duration for the speech, swallowing and hearing issues post-COVID-19, we conducted a three-phase study. In the first phase of the survey, 68 subjects reported symptoms related to speech, swallowing, and hearing issues 15 days of post-COVID recovery. A total of 76.4% of subjects reported only swallowing-related issues, 4.41% only speech-related issues, whereas 1.47% reported the problem in speech and hearing functions. The 2nd phase of the study was conducted after the first phase of the study. Only 22 subjects reported the presence of swallowing, speech and hearing-related issues from the 68 subjects. During the last phase, only 12 subjects reported speech, swallowing, and hearing issues. All subjects recovered from the olfaction and gustation impairment, whereas 50% of subjects reported the presence of xerostomia. From the present study, we conclude that the SARC-CoV-2 virus directly affects the respiratory system and affects the aero-digestive system and laryngeal system physiology. Individuals with comorbid conditions admitted in ICU during COVID-19 treatment and prolonged hospital stay were at higher risk of developing speech, swallowing, and hearing-related issues post-COVID-19. The present study indicated that all COVID-19 survivors should be screened for speech, swallowing, and hearing-related issues for early rehabilitation if needed.


KeMRE: Knowledge-enhanced medical relation extraction for Chinese medicine instructions.
Medicine instructions usually contain rich medical relations, and extracting them is very helpful for many downstream tasks such as medicine knowledge graph construction and medicine side-effect prediction. Existing relation extraction (RE) methods usually predict relations between entities from their contexts and do not consider medical knowledge. However, understanding a part of medical relations may need some expert knowledge in the medical field, making it challenging for existing methods to achieve satisfying performances of medical RE. In this paper, we propose a knowledge-enhanced framework for medical RE, which can exploit medical knowledge of medicines to better conduct medical RE on Chinese medicine instructions. We first propose a BERT-CNN-LSTM based framework for text modeling and learn representations of characters from their contexts. Then we learn representations of each entity by aggregating representations of their characters. Besides, we propose a CNN-LSTM based framework for entity modeling and learn entity representations from their relatedness. In addition, there are usually many different instructions for the same medicine, which usually share general knowledge on this medicine. Thus, to obtain medical knowledge of medicines, we annotate relations on a randomly-sampled instruction of each medicine. Then we build knowledge embeddings to represent potential relations between entities from knowledge of medicines. Finally, we use an MLP network to predict relations between entities from their representations and knowledge embeddings. Extensive experiments on a real-world dataset show that our method can significantly outperform existing methods.


Making BAC transgene constructs with lambda-red recombineering system for transgenic animals or cell lines.
The genomic DNA libraries based on Bacteria Artificial Chromosomes (BAC) are the foundation of whole genomic mapping, sequencing, and annotation for many species like mice and humans. With their large insert size, BACs harbor the gene-of-interest and nearby transcriptional regulatory elements necessary to direct the expression of the gene-of-interest in a temporal and cell-type specific manner. When replacing a gene-of-interest with a transgene in vivo, the transgene can be expressed with the same patterns and machinery as that of the endogenous gene. This chapter describes in detail a method of using lambda-red recombineering to make BAC transgene constructs with the integration of a transgene into a designated location within a BAC. As the final BAC construct will be used for transfection in cell lines or making transgenic animals, specific considerations with BAC transgenes such as genotyping, BAC coverage and integrity as well as quality of BAC DNA will be addressed. Not only does this approach provide a practical and effective way to modify large DNA constructs, the same recombineering principles can apply to smaller high copy plasmids as well as to chromosome engineering.


Mazindol self-administration in the rhesus monkey.
The ability of the intravenous administration of mazindol (SaH 42-548) to act as a reinforcer in monkeys previously conditioned to self-administer cocaine was ascertained. Unit dosages i.e. dosage per injection, of 50 and 100 mug/kg resulted in self-administration rates significantly greater than that which occurred with saline. An inverse relationship existed between unit dosage and frequency of self-administration over the unit dosage range 50-200 mug/kg. The total mazindol dosage self-administration per session was however independent of unit dosage. Approximately 2-3 mg/kg was self-administered by each animal during a 4 hr session at each of the 3 unit dosages. This tends to indicate that the 200 mug/kg unit dosage was also reinforcing even though the self-administration rate was similar to that of saline. This study indicates that mazindol can serve as a reinforcer and that the relationship between total session intake, unit dosage, and self-administration frequency of mazindol are similar to these seen with other reinforcing psychomotor stimulant drugs.


Antibiotic resistance heterogeneity and LasR diversity within Pseudomonas aeruginosa populations from pneumonia in intensive care unit patients.
This study investigated within-host heterogeneity of 66 Pseudomonas aeruginosa populations from pneumonia in 51 critically ill ventilated patients by examining 30 colonies per bronchoalveolar lavage (BAL). Differences in antibiotic susceptibility and quorum-sensing (QS) phenotypes were observed between the members of 14 (21.2%) and 10 (15.2%) populations, respectively. A significant association was found between QS deficiency and ceftazidime resistance. QS deficiency was associated with various lasR modifications, and was observed in 25 of 51 (49.0%) patients, including seven patients who received ≤48 h of ventilation. This study confirms the need to examine diverse colonies when analysing BAL cultures, particularly in β-lactam-exposed patients, to avoid missing ceftazidime- or imipenem-resistant isolates.


Probing Efficient N-Type Lanthanide Dopants for Mg3Sb2 Thermoelectrics.
The recent discovery of n-type Mg3Sb2 thermoelectrics has ignited intensive research activities on searching for potential n-type dopants for this material. Using first-principles defect calculations, here, a systematic computational screening of potential efficient n-type lanthanide dopants is conducted for Mg3Sb2. In addition to La, Ce, Pr, and Tm, it is found that high electron concentration (≳1020 cm-3 at the growth temperature of 900 K) can be achieved by doping on the Mg sites with Nd, Gd, Ho, and Lu, which are generally more efficient than other lanthanide dopants and the anion-site dopant Te. Experimentally, Nd and Tm are confirmed as effective n-type dopants for Mg3Sb2 since doping with Nd and Tm shows higher electron concentration and thermoelectric figure of merit zT than doping with Te. Through codoping with Nd (Tm) and Te, simultaneous power factor improvement and thermal conductivity reduction are achieved. As a result, high zT values of ≈1.65 and ≈1.75 at 775 K are obtained in n-type Mg3.5Nd0.04Sb1.97Te0.03 and Mg3.5Tm0.03Sb1.97Te0.03, respectively, which are among the highest values for n-type Mg3Sb2 without alloying with Mg3Bi2. This work sheds light on exploring promising n-type dopants for the design of Mg3Sb2 thermoelectrics.


Management issues related to effectively implementing a nutrition education program using peer educators.
To explore the influence of administrative aspects of a nutrition education program with peer educators delivering the program. Telephone interviews with peer educators trained to deliver La Cocina Saludable, a nutrition education program for Hispanics. Open- and closed-ended questions. Abuelas (grandmothers) recruited and trained as peer educators for the program. The sample included peer educators no longer teaching (22%), currently teaching (30%), and who never taught after training. Motives and incentives for becoming peer educators, challenges for peer educators, and reasons peer educators withdrew from the program. Descriptive statistics were used to analyze quantitative data from the closed-ended questions. Qualitative analysis was applied to data from open-ended questions. Working with community and learning about nutrition were prime motivators. Recruiting participants and coordination of classes appeared to be major challenges. Personal issues and traveling in a large geographic area were cited as the main reasons for quitting. The effectiveness of using peer educators for La Cocina Saludable may be improved through empowerment, additional training, a structured and equitable reimbursement system, and assistance to carry out administrative tasks.


The effect of child neglect and abuse information studies on parents' awareness levels during the COVID-19 pandemic.
The research was conducted in order to increase the knowledge and awareness of parents with children between the ages of 4-6 during the COVID-19 pandemic process, through social media applications and programs. The research was designed as a quasi-experimental study with pre-testing, post-testing, and control groups using a quantitative research method. There are 67 parents in the study group, 32 of which are experimental, and 35 are of a controlled group. Data was obtained using The Personal Information Form, Child Neglect and Abuse Awareness Scale for Parents, and Parental Abuse Scale. The "Child Neglect and Abuse WhatsApp and Online Education Program" was applied to the participants in the experimental group. Each day, three messages were sent to the participants in the experimental group on the subjects of child neglect, physical abuse, emotional abuse and sexual abuse, respectively. In addition, online training was given on the same subjects and in the same order in four sessions over the Zoom application. The participants in the control group did not receive any intervention. Before and after the implementation of the Child Neglect and Abuse WhatsApp and Online Education Program, data collection tools were given to the participants in the experimental and control groups. Paired samples t Test, Wilcoxon Signed Ranks Test were used to analyze the data. As a result of the study, there was no statistically significant difference between the pre-test scores and the post test scores of the parents in the control group. When the differences between the pre and post test scores of the parents in the experimental group and the pre and post tests scores of the parents in the experimental and control groups were compared, it was observed that there was a significant difference in favor of the experimental group. In line with this result, it can be said that the education applied has had an impact on the parents' knowledge and awareness of child neglect and abuse.


Transperitoneal versus retroperitoneal laparoscopic ureterolithotomy: a prospective randomized comparison study.
We compared laparoscopic transperitoneal and retroperitoneal ureterolithotomy approaches, and determined whether one technique is superior to the other. In this prospective randomized study from January 2009 to May 2012, 48 patients with proximal or mid ureteral stones underwent transperitoneal laparoscopic ureterolithotomy or retroperitoneal laparoscopic ureterolithotomy. The randomization occurred on a 1:1 basis. Groups 1 and 2 consisted of patients who underwent transperitoneal laparoscopic ureterolithotomy and retroperitoneal laparoscopic ureterolithotomy, respectively. Demographic and clinical characteristics as well as postoperative data were collected and analyzed. Statistical analysis was performed with SPSS® version 15.0 using the Fisher exact and Mann-Whitney U tests with p <0.05 considered statistically significant. The difference in visual pain analog score and mean tramadol requirement on days 1 and 2 between the 2 groups was statistically significant, and was higher in group 1 (p <0.05). Postoperative hospital stay and paralytic ileus rates were significantly higher in group 1 (p <0.05). The differences in total operative time and intracorporeal suturing time between the 2 groups were not statistically significant. However, successful stone removal was equal in the 2 groups. For proximal or mid ureteral large and impacted stones, transperitoneal laparoscopic ureterolithotomy is significantly associated with pain, greater tramadol requirement, ileus and longer hospital stay than retroperitoneal laparoscopic ureterolithotomy. However, successful stone removal remains the same in both groups.


Fluorescence detection of the transglycosylation activity of amylosucrase.
The purpose of this study was to investigate the novel fluorescence-based assay for the transglycosylation activity of amylosucrase (ASase). The transglycosylation activity of ASase from Deinococcus geothermalis (DGAS), ASase from Neisseria polysaccharea (NPAS), and DGAS-B (chimeric ASase wherein the B domain from DGAS was exchanged with the B domain of NPAS in a DGAS background) was applied to modify 4-methlylumberlliferone (MU) to 4-methylumberlliferone glucoside (MUG) using MU as an acceptor and sucrose as a glucoside donor. The result of HPLC (high performance liquid chromatography) show that the bioconversion of MUG with ASases was successfully accomplished using sucrose and MU. Kinetic studies of ASases were performed to determine kinetic parameter for sucrose and MU. The order of overall performance (kcat/Km) of transglycosylation activity for MU among DGAS, DGAS-B and NPAS was as follows: DGAS-B (8.1) > DGAS (5.0) > NPAS (0.4). The fluorescence-based transglycosylation assay using MU has a potential to be used as the detection of transglycosylation activity of ASase and to screen novel ASase variants, which may be improved in their transglycosylation activities.


Characterizing a transition from limited to unlimited diffusion in energy for a time-dependent stochastic billiard.
We explore Fermi acceleration in a stochastic oval billiard which shows unlimited to limited diffusion in energy when passing from the free to the dissipative case. We provide evidence for a transition from limited to unlimited energy growth taking place while detuning the corresponding restitution coefficient responsible for the degree of dissipation. A corresponding order parameter is suggested, and its susceptibility is shown to diverge at the critical point. We show that this order parameter is also be applicable to the periodically driven oval billiard and discuss the elementary excitation of the controlled diffusion process.


[Attention impairment in patients suffering from schizophrenia and their relatives of first-degree].
Attention dysfunction as assessed by standardised tests has often been reported in schizophrenic patients. Since many cognitive dysfunctions noted in these patients occur also in their close relatives, a supposition arises that they may be indicators not so much of transient states, but rather of a stable feature of cognitive functioning. This feature perhaps is transmitted from generation to generation and might contribute to the onset of the disease. A comparison of selected attention indicators in schizophrenic patients and their first-degree relatives with these in healthy controls without family history of schizophrenia. Participants in the study were 99 patients diagnosed with schizophrenia (according to the ICD-10-DCR criteria) in an early period of remission, their first-degree relatives (N = 56), out of whom 42 were healthy and 14 had a history of psychiatric disorders, and a control group of participants (N = 42) unrelated to the subjects and with no psychiatric history. Several tests of the computer-aided Vienna Test Battery were used, and namely: the RT test measuring reaction time to simple visual or auditory stimuli, and LVT test measuring the accuracy and performance time in a task that consisted in visual tracking of lines, and required concentration of visual perception. As compared to the controls, the patient group was found to manifest attention deficits in the form of longer reaction time to simple stimuli as well as increased performance time and decreased correctness of visual line tracking. The patients had also a somewhat longer reaction time to visual (but not auditory) stimuli, and their line tracking was inferior as compared to that of their healthy relatives. As regards the reaction time to simple stimuli, the latter did not differ significantly from the controls, but in the line tracking test which required more attention, their performance was significantly inferior to that of the control group.


Respiratory Disease in Migrant Farmworkers.
Respiratory problems are prevalent among persons who work in agriculture, however, publications examining the respiratory status in LatinX farmworkers are limited. The purpose of this study is to assess the respiratory status of LatinX farmworkers across New York State. This is a retrospective analysis of data gathered from Spanish language OSHA respiratory questionnaires completed between January 2017 and March 2019. The best of three peak flows were compared with predicted normal values derived from regressions using age, gender, and height. Key information was present in 162 Spanish questionnaires. Rates of reported respiratory symptoms were low, less than 2%; 11.7% farmworkers smoked. Best of three peak flows showed a mean of 97.2 ± 16.8% of predicted. New York LatinX farmworkers do not appear to have abnormal rates of respiratory symptoms or low peak flows.


Determining the Ratio of Wedge Height to Degree of Correction for Anterior Tibial Closing Wedge Osteotomies for Excessive Posterior Tibial Slope.
Anterior closing wedge osteotomy of the proximal tibia may be considered in revision anterior cruciate ligament (ACL) reconstruction surgery for patients with excessive posterior tibial slope (PTS). (1) To determine the ratio of wedge thickness to degrees of correction for supratubercle (ST) versus transtubercle (TT) osteotomies for anterior closing wedge osteotomies and (2) to evaluate the accuracy of ST and TT osteotomies in achieving slope correction. Controlled laboratory study. The computed tomography (CT) scans of 38 knees in 37 patients undergoing revision ACL reconstruction were used to simulate both ST and TT osteotomies. A 10° wedge was simulated in all CT models. The height of the wedge along the anterior tibia was recorded for each of the 2 techniques. The ratio of wedge height to achieved degree of correction was calculated. ST and TT osteotomies were performed on 3-dimensional (3D)-printed tibias of the 12 patients from the study group with the greatest PTS, after the desired degree of correction was determined. Pre- and postosteotomy slopes were measured for each tibia, and the actual change in slope was compared with the intended slope correction. According to CT measurements, the ratio of wedge height to degree of correction was 0.99 ± 0.07 mm/deg for the ST osteotomy and 0.83 ± 0.06 mm/deg for the TT osteotomy (P < .001). When these ratios were used to perform simulated osteotomies on the twelve 3D-printed tibias, the mean slope correction was within 1° to 2° of the intended slope correction, regardless of osteotomy location (ST or TT) or whether slope was measured on the medial or lateral plateau. The ST technique tended to undercorrect and the TT technique tended to overcorrect. When anterior tibial closing wedge osteotomies were removed to correct excessive PTS, removing a wedge with a ratio of 1 mm of wedge height for every 1° of intended correction for an ST technique and a ratio of 0.8 mm to 1° for a TT technique resulted in overall average slope correction within 1° to 2° of the target. The calculated ratios will allow clinicians to more accurately correct PTS when performing anterior closing wedge tibial osteotomy.


A novel HLA-A*33 allele, HLA-A*33:131, identified by sequencing-based typing.
The novel allele HLA-A*33:131 was identified in a Chinese individual using the sequencing-based typing method.


Testing an unusual in vivo vessel network model: a method to study angiogenesis in the colonial tunicate Botryllus schlosseri.
Tunicates are the closest relatives to vertebrates and include the only chordate species able to reproduce both sexually and asexually. The colonial tunicate Botryllus schlosseri is embedded in a transparent extracellular matrix (the tunic) containing the colonial circulatory system (CCS). The latter is a network of vessels external to zooids, limited by a simple, flat epithelium that originated from the epidermis. The CCS propagates and regenerates by remodelling and extending the vessel network through the mechanism of sprouting, which typically characterises vertebrate angiogenesis. In exploiting the characteristics of B. schlosseri as a laboratory model, we present a new experimental and analysis method based on the ability to obtain genetically identical subclones representing paired samples for the appropriate quantitative outcome statistical analysis. The method, tested using human VEGF and EGF to induce angiogenesis, shows that the CCS provides a useful in vivo vessel network model for testing the effects of specific injected solutes on vessel dynamics. These results show the potentiality of B. schlosseri CCS as an effective complementary model for in vivo studies on angiogenesis and anticancer therapy. We discuss this potentiality, taking into consideration the origin, nature, and roles of the cellular and molecular agents involved in CCS growth.


Shisa7 is a GABAA receptor auxiliary subunit controlling benzodiazepine actions.
The function and pharmacology of γ-aminobutyric acid type A receptors (GABAARs) are of great physiological and clinical importance and have long been thought to be determined by the channel pore-forming subunits. We discovered that Shisa7, a single-passing transmembrane protein, localizes at GABAergic inhibitory synapses and interacts with GABAARs. Shisa7 controls receptor abundance at synapses and speeds up the channel deactivation kinetics. Shisa7 also potently enhances the action of diazepam, a classic benzodiazepine, on GABAARs. Genetic deletion of Shisa7 selectively impairs GABAergic transmission and diminishes the effects of diazepam in mice. Our data indicate that Shisa7 regulates GABAAR trafficking, function, and pharmacology and reveal a previously unknown molecular interaction that modulates benzodiazepine action in the brain.


MLL1 is required for PAX7 expression and satellite cell self-renewal in mice.
PAX7 is a paired-homeobox transcription factor that specifies the myogenic identity of muscle stem cells and acts as a nodal factor by stimulating proliferation while inhibiting differentiation. We previously found that PAX7 recruits the H3K4 methyltransferases MLL1/2 to epigenetically activate target genes. Here we report that in the absence of Mll1, myoblasts exhibit reduced H3K4me3 at both Pax7 and Myf5 promoters and reduced Pax7 and Myf5 expression. Mll1-deficient myoblasts fail to proliferate but retain their differentiation potential, while deletion of Mll2 had no discernable effect. Re-expression of PAX7 in committed Mll1 cKO myoblasts restored H3K4me3 enrichment at the Myf5 promoter and Myf5 expression. Deletion of Mll1 in satellite cells reduced satellite cell proliferation and self-renewal, and significantly impaired skeletal muscle regeneration. Pax7 expression was unaffected in quiescent satellite cells but was markedly downregulated following satellite cell activation. Therefore, MLL1 is required for PAX7 expression and satellite cell function in vivo. Furthermore, PAX7, but not MLL1, is required for Myf5 transcriptional activation in committed myoblasts.


Clinicopathologic and Genomic Factors Impacting Efficacy of First-Line Chemoimmunotherapy in Advanced NSCLC.
Although programmed cell death protein 1 and programmed death-ligand 1 (PD-L1) blockade in combination with platinum-doublet chemotherapy has become a mainstay of first-line treatment for advanced NSCLC, factors associated with efficacy of chemoimmunotherapy (CIT) are not well characterized. In this multicenter retrospective analysis, clinicopathologic and genomic data were collected from patients with advanced NSCLC (lacking sensitizing genomic alterations in EGFR and ALK) and evaluated with clinical outcomes to first-line CIT. Among 1285 patients treated with CIT, a worsening performance status and increasing derived neutrophil-to-lymphocyte ratio in the blood were associated with a significantly reduced objective response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS). With increasing PD-L1 tumor proportion scores of less than 1%, 1% to 49%, 50% to 89%, and greater than or equal to 90%, there was a progressive improvement in ORR (32.7% versus 37.5% versus 51.6% versus 61.7%, p < 0.001), mPFS (5.0 versus 6.1 versus 6.8 versus 13.0 mo, p < 0.001), and generally mOS (12.9 versus 14.6 versus 34.7 versus 23.1 mo, p = 0.009), respectively. Of 789 NSCLCs with comprehensive genomic data, NSCLCs with a tumor mutational burden (TMB) greater than or equal to the 90th percentile had an improved ORR (53.5% versus 36.4%, p = 0.004), mPFS (10.8 versus 5.5 mo, p < 0.001), and mOS (29.2 versus 13.1 mo, p < 0.001), compared with those with a TMB less than the 90th percentile. In all-comers with nonsquamous NSCLC, the presence of an STK11, KEAP1, or SMARCA4 mutation was associated with significantly worse ORR, mPFS, and mOS to CIT (all p < 0.05); this was also observed in the KRAS-mutant subgroup of NSCLCs with co-occurring mutations in STK11, KEAP1, or SMARCA4 (all p < 0.05). In KRAS wild-type NSCLC, KEAP1 and SMARCA4 mutations were associated with a significantly shorter mPFS and mOS to CIT (all p < 0.05), but STK11 mutation status had no significant impact on mPFS (p = 0.16) or mOS (p = 0.38). In advanced NSCLC, better patient performance status, low derived neutrophil-to-lymphocyte ratio, increasing PD-L1 expression, a very high TMB, and STK11/KEAP1/SMARCA4 wild-type status are associated with improved clinical outcomes to first-line CIT.


IUPAB-serving the international biophysics community.
I have been invited, in my role as President of the International Union for Pure and Applied Biophysics, to provide a brief description of the activities of IUPAB and my own scientific journey.


Gene structure of human indoleamine 2,3-dioxygenase.
Two genomic DNA clones that encode human indoleamine 2,3-dioxygenase (IDO) were isolated from the human genomic DNA library using the IDO cDNA as a probe, and their restriction maps and partial nucleotide sequences were determined. The human IDO gene spanned 15 kilobase pairs with ten exons. The 5' terminus of the IDO mRNA was 33 nucleotides upstream of the translation initiation codon ATG. The 5' flanking region contained ISRE, X-box, and Y-box like sequences. Southern blot analysis of the human genomic DNA indicated that the human IDO gene was present in a single copy in the genome.


Isolation and selection of Bacillus spp. as potential biological agents for enhancement of water quality in culture of ornamental fish.
To isolate, select and evaluate Bacillus spp. as potential biological agents for enhancement of water quality in culture of ornamental fish. Natural isolates obtained from mud sediment and Cyprinus carpio were purified and assessed in vitro for efficacy based on the inhibition of growth of pathogenic Aeromonas hydrophila and the decrease in concentrations of ammonium, nitrite, nitrate and phosphate ions. Based on suitability to predefined characteristics, the isolates B001, B002 and B003 were selected and evaluated in vitro in the presence of Aer. hydrophila and in a preliminary in vivo trial with C. carpio. The inhibitory effect on pathogen growth and the decrease in concentrations of waste ions was demonstrated. Based on 16S RNA sequence homology, the isolates were identified as Bacillus subtilis, Bacillus cereus and Bacillus licheniformis, respectively. Isolate B002 did not contain the anthrax virulence plasmids pOX1, pOX2 or the B. cereus enterotoxin. Selected isolates effected synergistic reduction in pathogen load and the concentrations of waste ions in vitro and in vivo and are safe for use in ornamental aquaculture. A new approach for assessment of biological agents was demonstrated and has yielded putative isolates for development into aquaculture products.


Relationship between amplitude and timing of heart sounds and endocardial acceleration.
To study the correlation between heart sounds and peak endocardial acceleration (PEA) amplitudes and timings, by modulation of paced atrioventricular (AV) delay in recipients of dual chamber pacemakers. Ten recipients of dual chamber pacemakers implanted for high-degree AV block were studied. Endocardial acceleration (EA) and phonocardiographic and electrocardiographic signals were recorded during performance of an AV delay scan in VDD and DDD modes. First PEA (PEA I) and first heart sound (S1) changed similarly with the AV delay. A close intrapatient correlation was observed between S1 and PEA I amplitudes in all patients (P < 0.0001). The interpatient normalized PEA I to S1 amplitudes correlation was r = 0.89 (P < 0.0001) in DDD mode, and r = 0.81 (P < 0.0001) in VDD mode. The mean cycle-by-cycle PEA I to S1 delay was -4.3 +/- 22 ms and second PEA (PEA II) to second heart sound (S2) delay was -7.7 +/- 15 ms. A close correlation was observed between PEA I and S1 amplitudes and timings, and between PEA II and S2 timings. These observations support the hypothesis that PEA and heart sounds are manifestations of the same phenomena. EA might be a useful tool to monitor cardiac function.


First-ever stroke incidence and 30-day case fatality in the Sicilian Aeolian archipelago, Italy.
Not many data on stroke epidemiology come from studies on islands. This is the first report on a Mediterranean archipelago population. Using recommended criteria, from July 1, 1999, to June 30, 2002, information was collected on first-ever stroke and 30-day case fatality in Aeolian island residents (13,431). The overall crude incidence rate was 154 of 100,000 (95% CI, 118 to 197; 128 in men and 180 in women) or 180, 154, and 87, if adjusted to the Italian, European, and world populations, respectively. The 30-day case fatality rate was 24.2% (95% CI, 14.22 to 36.75). Besides genetic or dietary factors, our results may reflect local, limited possibilities of diagnosis and management for stroke patients.


Effect of Different Water Cooling Treatments on Changes in Rectal and Surface Body Temperature in Leisure Horses after Medium-Intensity Effort.
Cooling a horse after intensive exercise under hot conditions is commonly recommended. The study aimed to analyze changes in the rectal and surface temperature of the horses subjected to various water cooling treatments. This followed medium-intensity exercise performed by leisure horses under moderate air temperature. The experiment involved a control group without water application, and three variants of water cooling applied to 19 warmblood geldings after medium-intensity effort. Cooling of lower, upper, and lower and upper body parts was performed. In each variant, the rectal and body surface temperatures were measured five times: before; immediately after; and 10, 20, and 30 min after effort. Using water cooling under the studied conditions did not influence a post-exercise decrease in the rectal temperature. The decrease in body surface temperature depended on the used variant of cooling down the horse. Cooling the limbs by pouring water several times changed the surface body temperature from 34.2 ± 0.37 °C to 32.0 ± 0.32 °C and was more efficient than the repeated application of cool water on both the upper and lower body parts, leading to a temperature change from 34.6 ± 0.26 °C to 33.2 ± 0.36 °C. Thus, the application of cold water on the limbs only is sufficient for cooling the horse after medium-intensity exercise under moderate air temperature (about 24 °C).


Candida albicans requires iron to sustain hyphal growth.
Candida albicans is an important opportunistic fungal pathogen of immunocompromised individuals. The ability to switch between yeast and hyphal growth forms is critical for its pathogenesis. Hyphal development in C. albicans requires two temporally linked regulations for initiation and maintenance. Here, we performed transcriptome sequencing (RNA-Seq) to analyze the transcriptional consequences for the two different phases of hyphal development. Genome-wide transcription profiling reveals that the sets associated with hyphal initiation were significantly enriched in genes for hyphal cell wall, biofilm matrix and actin polarization. In addition to hypha-specific genes, numerous genes involved in iron acquisition, such as FTR1 and SEF1, are highly induced specifically during sustained hyphal development even when additional free iron is supplied in the medium. Therefore, iron uptake genes are induced by signals that can support prolonged hyphal development in an iron-independent manner. The induction of iron acquisition genes during hyphal elongation was further confirmed by quantitative reverse transcription-PCR under various hypha-inducing conditions. Remarkably, preventing C. albicans from acquiring iron blocks BRG1 activation, leading to impaired hyphal maintenance, and ectopically expressed BRG1 can sustain hyphal development bypassing the requirement of iron. Our study elucidates an underlying mechanism of how multiple virulence factors are interconnected and are induced simultaneously during infection.


GFAKluge: A C++ library and command line utilities for the Graphical Fragment Assembly formats.
GFA has emerged as a standard format for the exchange of genome assemblies and sequence graphs. To encourage further adoption in high-performance software we have developed an open-source C++ library for GFA and a set of utilities for summarizing and manipulating the format. The gfakluge source code is freely available under the MIT license at https://github.com/edawson/gfakluge. It has been tested on both Mac OS X and Linux.


The human histone gene expression regulator HBP/SLBP is required for histone and DNA synthesis, cell cycle progression and cell proliferation in mitotic cells.
Histone proteins are essential for chromatin formation, and histone gene expression is coupled to DNA synthesis. In metazoans, the histone RNA binding protein HBP/SLBP is involved in post-transcriptional control of histone gene expression. In vitro assays have demonstrated that human HBP/SLBP is involved in histone mRNA 3' end formation and translation. We have inhibited human HBP/SLBP expression by RNA interference to determine its function during the mitotic cell cycle. Inhibition of HBP/SLBP expression resulted in the inhibition of histone gene expression and DNA synthesis, the inhibition of cell cycle progression in S phase and the inhibition of cell proliferation. These findings indicate that human HBP/SLBP is essential for the coordinate synthesis of DNA and histone proteins and is required for progression through the cell division cycle.


A Nanopore Sequencing Course for Graduate School Curriculum.
The high-throughput long-read sequencing has become affordable enough for any molecular biology lab to utilize genome sequencing in their research. Complete genome sequencing and assembly of bacterial genomes is one such application which is powerful yet simple enough for anyone without advanced molecular biology or bioinformatics skills to conduct on his/her own. High-throughput sequencing will eventually become a basic routine tool in molecular biology labs just like polymerase chain reaction and electrophoresis in a near future. To assist the use of such nanopore sequencing technologies, we designed a graduate school course to learn both the experimental and bioinformatic skills of complete bacterial genome sequencing and assembly.


Implantation of a dual-chamber pacemaker in a patient with persistent left superior vena cava using a a steerable stylet.
A persistent left superior vena cava (PLSVC) is a rare abnormality that presents a challenge to the implanter. To our knowledge, this is the first case report of implantation of dual-chamber pacemaker via PLSVC utilizing a steerable stylet (the Locater; St. Jude Medical, Inc., Minnetonka, Minnesota) with chronic follow-up showing stable threshold.


Cardamomin protects from diabetes-induced kidney damage through modulating PI3K/AKT and JAK/STAT signaling pathways in rats.
Diabetic nephropathy is one of the common complications of diabetes mellitus, which seriously affects the life quality and health of patients. In this study, we aimed to investigate the function of cardamonin (CAD) in diabetes-induced kidney damage in rats. The normal rat kidney tubular epithelial cells (NRK-52E) were pre-treated with different doses of CAD and then stimulated with methylglyoxal (MGO). Streptozotocin (STZ) induced diabetes rat model were received different doses of CAD treatment. MTT, EdU, Transwell, and flow cytometry was used to detect cell viability, proliferation, migration, and apoptosis. Western blot analysis was used to detect the expression of apoptosis related proteins, advanced glycation end-products (AGEs), receptor for AGEs (RAGE), epithelial mesenchymal transition (EMT) related proteins, phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway related proteins, and janus kinas/signal transducer and activator of transcription 3 (JAK/STAT3) related proteins. ELISA assay was used to detect the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). The levels of malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) were detected using commercial kit. Hematoxylin and eosin staining was used to assess pathological changes in rat kidney. Compared with control group, MGO reduced cell viability and proliferation, enhanced migration and apoptosis of NRK-52E cells, while CAD inhibited these effects induced by MGO in NRK-52E cells. Moreover, CAD increased Bcl-2 expression and decreased the expression of Bax and cleaved caspase-3 in MGO-treated NRK-52E cells. Compared with control group, MGO increased the AGEs formation, the expression of RAGE and p-p65, the levels of TNF-α, IL-6, IL-1β, MDA in NRK-52E cells and reduced the levels of GSH and SOD, while treatment of CAD dose-dependently prevented these results. In addition, CAD attenuated MGO-induced EMT of MGO-treated NRK-52E cells. Mechanically, we identified that CAD repressed PI3K/AKT and JAK/STAT3 signaling in NRK-52E cells. Importantly, the kidney injury of diabetes rats was attenuated by CAD. Besides, STZ-induced inflammatory response, oxidative stress, and phosphorylation levels of PI3K, AKT, JAK2, and STAT3 were reduced by CAD in the rats. CAD protects from diabetes-induced kidney damage through modulating PI3K/AKT and JAK/STAT signaling pathways in rats.


Codiaeum variegatum (L.) Rumph. ex A. Juss. (Euphorbiaceae): An overview of its botanical diversity, traditional uses, phytochemistry, pharmacological effects and perspectives towards developing its plant-based products.
Codiaeum variegatum also called miracle shrub, is a plant species constituted of more than 300 cultivars which are mostly used as indoor plants for decoration. However, some of these varieties are used by indigenous populations for the treatment of diarrhoea, stomach ache, external wounds, intestinal worms and ulcers. This study describes an overview of the botanical diversity, medicinal uses, phytochemical composition of C. variegatum. Then it critically discusses its pharmacological activities versus toxic potential and new perspectives are suggested for the development of its plant-based products. A bibliographic assessment of publications on C. variegatum indexed in Google Scholar, PubMed, Science Direct, Scopus, Springer Link, and Web of Science online databases was conducted from 1970 to 2020, and 89 relevant articles related to the botanical diversity (17), traditional uses (22), phytochemical analysis (11), pharmacological activity (31) and toxicity profile (18) of C. variegatum were selected for this review. Most commonly, it was found that aqueous leaf extracts or decoctions of C. variegatum are used in traditional medicine to treat amoebic dysentery and stomach ache while a bath with root decoction or sap is applied in small quantities on skin related infections. A total of 14 identified and 24 non-identified varieties of C. variegatum were reported for pharmacological activity, and prominent research topics include the anti-amoebic, antimicrobial, antiviral and cytotoxic activities. Alkaloids (3), terpenoids (5) and phenolics (15) were the major compounds identified, and a new antiviral cyanoglucoside was isolated from the sap of C. variegatum. Toxic substances (5-deoxyingenol and phorbol esters) were found in some varieties used as ornamental plants, but the Mollucanum variety used in traditional medicine was found to be safe. The present review revealed that the native variety of C. variegatum (cv. Mollucanum) can be used to treat amoebic dysentery. Alkaloids, terpenoids and phenolic compounds have been characterized in this plant species while other classes of phytochemicals are not yet investigated. The development of new cultivars recommends an in-depth toxicological study before any use. No clinical trial has been reported to date, and further studies are needed to evaluate other claimed medicinal uses. Due to its efficacy and safety, the Mollucanum variety is most likely suitable for the development of a medicine against amoebiasis, which will surely lay the foundation for clinical studies.


Polymicrobial Gardnerella biofilm resists repeated intravaginal antiseptic treatment in a subset of women with bacterial vaginosis: a preliminary report.
Bacterial vaginosis is a recalcitrant polymicrobial biofilm infection that often resists standard antibiotic treatment. We therefore considered repeated treatment with octenidine, a local antiseptic that has previously been shown to be highly effective in several biofilm-associated infections. Twenty-four patients with recurrent BV were treated with a 7-day course of octenidine (octenidine dihydrochloride spray application with the commercial product Octenisept). In case of treatment failure or relapse within 6 months, patients were re-treated with a 28-day course of octenidine. In case of recurrence within 6 months after the second treatment course, patients were treated again with a 28-day course followed by weekly applications for 2 months. Treatment effect was evaluated by assessment of the presence of the biofilm on voided vaginal epithelial cells through fluorescence in situ hybridisation. The initial cure rate following a 7-day course of octenidine was as high as 87.5%. The 6-month relapse rate was, however, as high as 66.6%. Repeated treatment for 28 days led to an overall cure rate of 75.0%; however, it was also associated with emergence of complete resistance to octenidine in a subset of women. The overall cure rate after three treatment courses with 1-year follow-up was 62.5 %, with 37.5 % of the patients showing complete resistance to octenidine. Our preliminary results showed that octenidine dihydrochloride was initially highly effective, but the efficacy of repeated and prolonged treatment dropped quickly as challenge with the antiseptic rapidly led to bacterial resistance in a considerable subset of women.


[Interest of Apremilast in idiopathic recurrent aphthous stomatitis: Review of two clinical cases].
Apremilast is a phosphodiesterase 4 inhibitor used in psoriasis and psoriatic arthritis Recently, this treatment has received marketing authorization for severe and refractory oral aphthosis in Behçet's disease. Idiopathic recurrent aphthous stomatitis (RAS) outside of Behçet's disease is often difficult to treat and can affect patients' quality of life. We report our experience with the use of apremilast in two 49-year-old patients with refractory oral aphthosis not related to Behçet's disease or another etiology. In both cases, a combination of apremilast with low-dose prednisone controlled the idiopathic RAS within a few weeks. Apremilast, which already has marketing authorization for Behçet's disease, also appears to be effective in RAS.


"We charge them; otherwise we cannot run the hospital" front line workers, clients and health financing policy implementation gaps in Ghana.
This paper examines policy implementation gaps of user fees plus exemptions and health insurance in providing financial access to primary clinical care for children under five in Ghana. Methods included analysis of routine data, focus group discussions, in-depth interviews, and administration of a structured questionnaire. Providers modified exemptions policy implementation arrangements, sometimes giving partial or no exemptions. Clients who knew or suspected exemption entitlements failed to request them because of fear of negative reactions from providers. Providers attributed their modification of implementation arrangements and negative reactions to the threat posed to the financial viability of their institutions by reimbursement uncertainty and delays. At the time of the study insurance coverage was low and frontline workers were not noticeably modifying implementation arrangements. However, the underlying goal conflicts, resource scarcity, conditions of work and relationships between frontline workers and clients that fueled the exemptions policy implementation gaps were unchanged. The potential for the health insurance policy to stumble over implementation gaps as happened with the exemptions policy therefore remained. Policies that do not take into account the incentives for frontline worker adherence and align them better with policy objectives may experience implementation gaps.


Evidence that human placenta is a site of sex hormone-binding globulin gene expression.
The presence of an androgen-binding component in placenta was investigated in vitro using a tissue culture system of human placental explants. Explants of trophoblastic tissue from normal term placentas were kept in culture under appropriate conditions for at least 48 h in a serum-free medium. The existence of an androgen-binding protein was explored by binding assays, immunohistochemistry studies and Northern blot analyses of placental mRNA. Steady-state polyacrylamide gel electrophoresis and Scatchard plot analyses revealed the presence of a high affinity specific binding component for 5 alpha-dihydrotestosterone in cultured placenta. Immunohistochemical studies performed on intact placenta and on Percoll-gradient purified trophoblastic cells demonstrated the presence of specific immunoreactivity in the cytoplasm of syncytial cells. Northern blot analyses of placental mRNA showed a single hybridizable 32P-labeled human sex hormone-binding globulin (SHBG) cDNA band of approx. 1.6 kb which was identical in size to that obtained with liver mRNA. The results strongly suggest the placenta as an origin of SHBG and point out this tissue as an additional site of SHBG synthesis during pregnancy.


Phosphate content of mammalian neurofilaments.
The phosphate content of neurofilaments from bovine spinal cord and of their constituent polypeptides was determined. Neurofilament preparations, as isolated, contained substantial amounts of phosphate, having between 65 and 98 nmol of phosphate/mg of protein. When the polypeptides of the neurofilament were assayed for phosphate individually, the 210,000-and 160,000-dalton polypeptides were found to possess large numbers of phosphate groups, while the 68,000-dalton polypeptide had less than 1 mol of phosphate/mol of polypeptide. The 210,000-dalton polypeptide had about 104 mol of phosphate bound/mol of polypeptide, and the 160,000-dalton polypeptide had about 26 mol of phosphate/mol of polypeptide. This distribution of phosphate among the polypeptides of the neurofilament preparation was qualitatively confirmed when sodium dodecyl sulfate-polyacrylamide gels of the preparations were stained for phosphate. Bands corresponding to the 210,000- and 160,000-dalton polypeptides were readily detected. No other phosphate-stained bands were seen, even on heavily loaded gels.