Risk-related standards of competence: continuing the debate over risk-related standards of competence.
This discussion paper addresses Ian Wilks' defence of the risk-related standard of competence that appears in Bioethics 11. Wilks there argues that the puzzle posed by Mark Wicclair in Bioethics 5 against Dan Brock's argument in favour of a risk-related standard of competence -- namely that Brock's argument allows for situations of asymmetrical competence -- is not a genuine problem for a risk-related standard of competence. To show this, Wilks presents what he believes to be two examples of real situations in which asymmetrical competence arises. I argue that insofar as Wilks equivocates two senses of competence in his examples -- namely, competence to perform a task and competence in performing a task -- Wilks is unable to illustrate the existence of real situations of asymmetrical competence. By examining the way in which Wilks equivocates two senses of competence in his examples, and by applying the results of this examination to the problem of patient competency within the medical field, I argue that not only does Wilks fail to show that situations of asymmetrical competence exist, but he is also unable to provide a foundation for understanding how the risk-related standard of competence can strike a balance between an individual's autonomy and benevolent intervention. I thus conclude that insofar as Wilks fails to answer the objections raised by Wicclair and others against the risk-related standard of competence, the risk-related standard of competence continues to be undermined by the problem of asymmetrical competence.


Verification of propofol sulfate as a further human propofol metabolite using LC-ESI-QQQ-MS and LC-ESI-QTOF-MS analysis.
Propofol (2,6-diisopropylphenol) is a water-insoluble, intravenous anesthetic that is widely used for the induction and maintenance of anesthesia as well as for endoscopic and pediatric sedation. After admission, propofol undergoes extensive hepatic and extrahepatic metabolism, including direct conjugation to propofol glucuronide and hydroxylation to 2,6-diisopropyl-1,4-quinol. The latter substance subsequently undergoes phase II metabolism, resulting in the formation of further metabolites (1quinolglucuronide, 4quinolglucuronide and 4quinol-sulfate). Further minor phase I propofol metabolites (2-(ω-propanol)-6-isopropylphenol and 2-(ω-propanol)-6-isopropyl-1,4-quinol)) are also described. Due to its chemical structure with the phenolic hydroxyl group, propofol is also an appropriate substrate for sulfation by sulfotransferases. The existence of propofol sulfate was investigated by liquid chromatography electrospray ionization triple quadrupole mass spectrometry (LCESIQQQ-MS) and liquid chromatography electrospray ionization quadrupole time-of-flight mass spectrometry (LCESI-QTOF-MS). A propofol sulfate reference standard was used for identification and method development, yielding a precursor at m/z 257 (deprotonated propofol sulfate) and product ions at m/z 177 (deprotonated propofol) and m/z 80 ([SO3]-). Propofol sulfate - a further phase II metabolite of propofol - was verified in urine samples by LC-ESI-QQQ-MS and LC-ESI-QTOF-MS. Analyses of urine samples from five volunteers collected before and after propofol-induced sedation verified the presence of propofol sulfate in urine following propofol administration, whereas ascertained concentrations of this metabolite were significantly lower compared with detected propofol glucuronide concentrations. The existence of propofol sulfate as a further phase II propofol metabolite in humans could be verified by two different detection techniques (LCESIQQQ-MS and LC-ESI-QTOFMS) on the basis of a propofol sulfate reference standard. Evaluation of the quantitative analyses of propofol sulfate imply that propofol sulfate represents a minor metabolite of propofol and is only slightly involved in human propofol clearance.


Assessment of knowledge of Iranian occupational therapists of handling of children with cerebral palsy.
The purpose of this study was to assess the knowledge of Iranian occupational therapists regarding the handling of children with cerebral palsy and the application of their knowledge into practice. A questionnaire with two scales of a self-report and a knowledge-based test was designed. Data were analysed by using descriptive statistics and Spearman correlation. Of 77 participants, 64.9% participants reported their knowledge of handling at moderate, 14.3% at low and 6.5% at very low level. The result of the test showed that 57.1% participants had knowledge at moderate and 16.9% at low level. Toileting and bathing are the least focused areas by occupational therapists in teaching handling techniques to caregivers. These results suggest that the participants need further training to increase their knowledge in the various areas of handling and positioning techniques especially toileting and bathing. Because participants were from one area of Iran, future research could include a larger population of occupational therapists.


Targeting Fyn Kinase in Alzheimer's Disease.
The past decade has brought tremendous progress in unraveling the pathophysiology of Alzheimer's disease (AD). While increasingly sophisticated immunotherapy targeting soluble and aggregated brain amyloid-beta (Aβ) continues to dominate clinical research in AD, a deeper understanding of Aβ physiology has led to the recognition of distinct neuronal signaling pathways linking Aβ to synaptotoxicity and neurodegeneration and to new targets for therapeutic intervention. Identifying specific signaling pathways involving Aβ has allowed for the development of more precise therapeutic interventions targeting the most relevant molecular mechanisms leading to AD. In this review, I highlight the discovery of cellular prion protein as a high-affinity receptor for Aβ oligomers, and the downstream signaling pathway elucidated to date, converging on nonreceptor tyrosine kinase Fyn. I discuss preclinical studies targeting Fyn as a therapeutic intervention in AD and our recent experience with the safety, tolerability, and cerebrospinal fluid penetration of the Src family kinase inhibitor saracatinib in patients with AD. Fyn is an attractive target for AD therapeutics, not only based on its activation by Aβ via cellular prion protein but also due to its known interaction with tau, uniquely linking the two key pathologies in AD. Fyn is also a challenging target, with broad expression throughout the body and significant homology with other members of the Src family kinases, which may lead to unintended off-target effects. A phase 2a proof-of-concept clinical trial in patients with AD is currently under way, providing critical first data on the potential effectiveness of targeting Fyn in AD.


Induction of nuclear factor kappa B after low-dose ionizing radiation involves a reactive oxygen intermediate signaling pathway.
Reactive oxygen intermediates (ROIs) have been found to be the messengers in the activation of the kappa B transcription regulator in mitogen- or cytokine-stimulated cells, operating in conjunction with or independently of various other mechanisms; these include Ca(++)-dependent and PKC-dependent cytoplasmic signaling pathways. We have recently reported that low-dose ionizing radiation induces NF-kappa B in human lymphoblastoid 244B cells. Since ionizing radiation generates free radicals in cells, we have investigated whether the ROIs generated by ionizing radiation induce NF-kappa B activity, and also whether they do so by a similar mechanism as in cells treated with PMA or H2O2. The results not only confirm a previous observation from our laboratory that low-dose ionizing radiation (0.1-2.0 Gy) activates kappa B transcription factor transiently with a maximal induction at 0.5 Gy exposure, but also demonstrate mechanistically that the activation of NF-kappa B by low-dose ionizing radiation can be inhibited considerably by the antioxidant N-acetyl-L-cysteine, indicating that at least the major part of the activation process is mediated by ROIs. These findings support the idea that ROIs can regulate the kappa B elements which in turn can serve as response elements for oxidant stress.


Regulatory Roles of Drosophila Insulin-Like Peptide 1 (DILP1) in Metabolism Differ in Pupal and Adult Stages.
The insulin/IGF-signaling pathway is central in control of nutrient-dependent growth during development, and in adult physiology and longevity. Eight insulin-like peptides (DILP1-8) have been identified in Drosophila, and several of these are known to regulate growth, metabolism, reproduction, stress responses, and lifespan. However, the functional role of DILP1 is far from understood. Previous work has shown that dilp1/DILP1 is transiently expressed mainly during the pupal stage and the first days of adult life. Here, we study the role of dilp1 in the pupa, as well as in the first week of adult life, and make some comparisons to dilp6 that displays a similar pupal expression profile, but is expressed in fat body rather than brain neurosecretory cells. We show that mutation of dilp1 diminishes organismal weight during pupal development, whereas overexpression increases it, similar to dilp6 manipulations. No growth effects of dilp1 or dilp6 manipulations were detected during larval development. We next show that dilp1 and dilp6 increase metabolic rate in the late pupa and promote lipids as the primary source of catabolic energy. Effects of dilp1 manipulations can also be seen in the adult fly. In newly eclosed female flies, survival during starvation is strongly diminished in dilp1 mutants, but not in dilp2 and dilp1/dilp2 mutants, whereas in older flies, only the double mutants display reduced starvation resistance. Starvation resistance is not affected in male dilp1 mutant flies, suggesting a sex dimorphism in dilp1 function. Overexpression of dilp1 also decreases survival during starvation in female flies and increases egg laying and decreases egg to pupal viability. In conclusion, dilp1 and dilp6 overexpression promotes metabolism and growth of adult tissues during the pupal stage, likely by utilization of stored lipids. Some of the effects of the dilp1 manipulations may carry over from the pupa to affect physiology in young adults, but our data also suggest that dilp1 signaling is important in metabolism and stress resistance in the adult stage.


Serum free testosterone, leptin and soluble leptin receptor changes in a 6-week strength-training programme.
Strength training is usually associated with a reduction in fat mass and with muscle hypertrophy. The aim of the present study was to examine whether the serum free leptin index (FLI), measured by the molar excess of soluble leptin receptor (sOB-R) over leptin, is increased by 6 weeks of strength training. Eighteen male, physical education students were randomly assigned to two groups: a strength-training (n 12) and a control group (n 6). Body composition (lean body mass and body fat) determined by dual-energy X-ray absorptiometry (DXA), muscle performance and leptin, sOB-R, total testosterone and free testosterone concentrations were determined before and after training. Fat mass was reduced by 1 kg with strength training (P<0.05). Lean body mass of trained extremities was increased by 3% (P<0.05), while the concentration of free testosterone in serum was reduced by 17% (P<0.05) after training. However, despite the reduction in fat mass and free testosterone, serum leptin concentration was not significantly affected by strength training, even after accounting for the differences in body fat. By contrast, for a given fat mass, the sOB-R was increased by 13% (P<0.05) at the end of the strength-training programme, although the molar excess of sOB-R over leptin remained unchanged. Therefore, the quantity of free leptin available to bind to the target tissues was not significantly affected by the short strength-training programme, which elicited a 7% reduction in fat mass.


Aptamer-modified PLGA nanoparticle delivery of triplex forming oligonucleotide for targeted prostate cancer therapy.
Presented study aimed to prepare A10 aptamer-modified poly (D,L-lactic-co-glycolic acid) (PLGA) nanoparticles loaded with triplex forming oligonucleotides(TFO) for targeted prostate cancer therapy. We first synthesized a PLGA-PEG-Apt copolymer. The PLGA-PEG-Apt nanoparticles (NP-Apt) were loaded with TFO using double emulsion solvent evaporation method. Carboxy-fluorescein labeled TFO-NP-Apt, TFO-NP and TFO were prepared for cellular uptake experiments. Cell counting kit-8 (CCK-8) test was used to determine the ability of TFO-NP-Apt to inhibit LNCaP cell proliferation. RT-PCR and Western blot was conducted to analyze AR gene expressing. Then, a mouse model of prostate cancer was used to evaluate the anti-cancer effect of TFO-NP-Apt in vivo. We confirmed that the PLGA-PEG-Apt conjugation was successful. The TFO encapsulation efficiency and drug loading percentage were 46.1± 3.6% and 40.8±5.3%, respectively. TFO-NP-Apt showed a more efficient cellular uptake than TFO-NP or TFO in LNCaP cells. TFO-NP-Apt was significantly more cytotoxic than TFO-NP and TFO in the CCK-8 test (p<0.001). TFO-NP-Apt silenced the AR gene better than unconjugated Apt, naked TFO, NP or saline. TFO-NP-Apt were more effective than TFO-NP, naked TFO, NP and saline at inhibiting prostate cancer growth in vivo (p<0.05). Aptamer-modified TFO-loaded PLGA nanoparticles may prove useful in targeted therapy for advanced prostate cancer.


Reducible Dimeric Conjugates of Small Internally Segment Interfering RNA for Efficient Gene Silencing.
The condensation of nucleic acids into compact nanoparticles with cationic carriers is a powerful tool for translocating exogenous nucleic acids into cells. To date, most efforts have been focused on the development of novel gene carriers for safe and efficient gene delivery. However, small interfering RNA (siRNA) is generally not strongly associated with cationic carriers due to its stiff structure and low spatial charge density. To overcome this limitation, this work introduces a well-defined dimeric conjugate of small internally segment interfering RNA (sisiRNA) linked via a disulfide bond for enhanced cellular uptake and gene silencing. Dimeric sisiRNA is synthesized through oxidizing two monomeric sisiRNA molecules, each of which consists of a sense strand carrying a nick and an antisense strand modified with a thiol group at the 3'-end. The nick in the sense strand enables the dimeric sisiRNA to be more effectively condensed into nanosized complexes due to the increased structural flexibility, which results in a higher gene silencing efficiency compared with the dimeric siRNA containing the intact sense strands. The results indicate that the discontinuity of the sense strands is a simple method of adding more flexibility to various siRNA-based nanostructures for enhanced gene silencing.


Microcanonical finite-size scaling in second-order phase transitions with diverging specific heat.
A microcanonical finite-size ansatz in terms of quantities measurable in a finite lattice allows extending phenomenological renormalization (the so-called quotients method) to the microcanonical ensemble. The ansatz is tested numerically in two models where the canonical specific heat diverges at criticality, thus implying Fisher renormalization of the critical exponents: the three-dimensional ferromagnetic Ising model and the two-dimensional four-state Potts model (where large logarithmic corrections are known to occur in the canonical ensemble). A recently proposed microcanonical cluster method allows simulating systems as large as L=1024 (Potts) or L=128 (Ising). The quotients method provides accurate determinations of the anomalous dimension, eta, and of the (Fisher-renormalized) thermal nu exponent. While in the Ising model the numerical agreement with our theoretical expectations is very good, in the Potts case, we need to carefully incorporate logarithmic corrections to the microcanonical ansatz in order to rationalize our data.


Impact of maxillary sinus augmentation on oral health-related quality of life.
The aim of this study was to measure the oral health-related quality of life (OHRQoL) after maxillary sinus augmentation to determine the physical and psychological impact of this procedure for the patient. Three hundred sixteen patients treated with an external or internal maxillary sinus augmentation and a total of 863 implants in the Department of Oral and Maxillofacial Surgery, Johannes Gutenberg University, Mainz, Germany, between July 2002 and December 2007 were included in this retrospective study. Total implant survival was assessed. Completion of a modified 26-item version of the Oral Health Impact Profile (OHIP-G) for assessing the oral health-related quality of life before and after the treatment was asked for. Subcategories were (1) functional limitations, (2) physical and psychological disabilities, and (3) complaints due to the surgical procedure. In 53 patients available for clinical follow-up examination, assessment of soft tissue parameters was performed. After an average time in situ of 41.2 ± 27 months (3.4 years), the in situ rate was 95.4%. One-year survival rate and five-year survival rate according to Kaplan Meier were 95.4 and 94.4%. Concerning functional limitations, significant better values for OHRQoL after sinus augmentation procedure than before the treatment (p < 0.001) were seen. In the subcategory physical and psychological disabilities, all questions had significant better values after the sinus lift (p < 0.001). Concerning complaints due to the surgical procedure, mean total scores were 5.1 ± 5.4 pre-operative, 6.9 ± 6.1 (0-31) post-operative, and 2.4 ± 3.7 recently. This meant a significant difference between "pre-operative" vs. "post-operative" (p = 0.003), "pre-operative" vs. "recently" (p < 0.001), and "post-operative" vs. "recently" (p < 0.001). Concerning the influence of implant indication, edentulous patients showed the most distinct improvement after the procedure. Clinical assessment showed stable soft tissue parameters. Evaluation of OHRQoL after sinus augmentation showed a significant improvement indicating a remarkable benefit for the patients through this procedure.


Botryllus schlosseri: a model ascidian for the study of asexual reproduction.
Botryllus schlosseri, a cosmopolitan colonial ascidian reared in the laboratory for more than 50 years, reproduces both sexually and asexually and is used as a model organism for studying a variety of biological problems. Colonies are formed of numerous, genetically identical individuals (zooids) and undergo cyclical generation changes in which the adult zooids die and are replaced by their maturing buds. Because the progression of the colonial life cycle is intimately correlated with blastogenesis, a shared staging method of bud development is required to compare data coming from different laboratories. With the present review, we aim (1) to introduce B. schlosseri as a valuable chordate model to study various biological problems and, especially, sexual and asexual development; (2) to offer a detailed description of bud development up to adulthood and the attainment of sexual maturity; (3) to re-examine Sabbadin's (1955) staging method and re-propose it as a simple tool for in vivo recognition of the main morphogenetic events and recurrent changes in the blastogenetic cycle, as it refers to the developmental stages of buds and adults.


Separation of low molecular weight RNA species by high-speed gel filtration.
By employing a high-speed gel filtration method using a column of silica-based aqueous gel, TSK-GEL G 300 SW, the three low molecular weight RNA species, 5.8S and 5S rRNA, and tRNA, were clearly separated from each other and from high molecular weight RNA species in 200 mM sodium phosphate buffer, pH 7.0, containing 0.1% SDS. Excellent reproducibility and resolution were obtained under these conditions, about 30 min being required for a single run. Furthermore, the 5.8S rRNA from rat liver cells was eluted at a different position compared with that of the yeast, Saccharomyces cerevisiae, although they have the same nucleotide chain length but at different sequence. The 5.8S rRNA from the cellular slime mold, Dictyostelium discoideum, was eluted at the same position as that of yeast.


EphrinB-EphB Signaling Induces Hyperalgesia through ERK5/CREB Pathway in Rats.
There are numerous studies implicating that EphB receptors and ephrinB ligands play important roles in modulating the transduction of spinal nociceptive information. EphrinB-EphB signaling may contribute to hyperalgesia via various kinds of downstream molecules, the mechanisms of which have not been completely understood. The aim of the present study was to identify whether ephrinB-EphB signaling could contribute to hyperalgesia through ERK5/CREB pathway. Controlled animal study. University laboratory. This study attempted to detect the changes of pain behaviors and the protein level of p-ERK5 and p-CREB by activating EphB receptors in the spinal cord of rats. To further confirm our hypothesis, we designed LV-siRNA for knockdown of spinal ERK5. When ERK5 was inhibited, we recorded the changes of spinal p-CREB expression and the pain behaviors of rats after activating EphB receptors. We also confirmed this conclusion in rat CCI model. Statistical analyses were performed using GraphPad Prism 5. Intrathecal injection of ephrinB2-Fc in rats evoked thermal hyperalgesia and mechanical allodynia, along with activation of ERK5 and CREB in the spinal cord. Knockdown of ERK5 inhibited ephrinB2-Fc-induced CREB activation and hyperalgesia. Blocking EphB receptors prevented CCI-induced neuropathic pain and spinal ERK5/CREB activation. More underlying mechanisms that underlie the relationship between ephrinB-EphB signaling and ERK5/CREB pathway will need to be explored in future studies. Our study suggests that ERK5/CREB pathway plays important roles in the transduction of nociceptive information associated with ephrinB-EphB signaling. This study provides further understanding of the downstream mechanisms of ephrinB-EphB signaling and helps to explore new targets for treating pathological pain.


Robotic versus Freehand Needle Positioning in CT-guided Ablation of Liver Tumors: A Randomized Controlled Trial.
Purpose To compare the accuracy of freehand versus robotic antenna placement in CT-guided microwave ablation (MWA) of liver tumors. Materials and Methods This study was conducted as a prospective single-center nonblinded randomized controlled trial (Netherlands Trial Registry, NTR6023). Eligible study participants had undergone clinically indicated CT-guided MWA of liver tumors and were able to receive a CT contrast agent. Randomization was performed per tumor after identification on contrast material-enhanced CT images. The primary outcome was the number of antenna repositionings, which was compared by using the Mann-Whitney U test. Secondary outcomes were lateral targeting error stratified by in-plane and out-of-plane targets and targeting time. Results Between February 14 and November 12, 2017, 31 participants with a mean age of 63 years (range, 25-88 years) were included: 17 women (mean age, 57 years; range, 25-77 years) and 14 men (mean age, 70 years; range, 52-88 years). The freehand study arm consisted of 19 participants, while the robotic study arm consisted of 18 participants; six participants with multiple tumors were included in both arms. Forty-seven tumors were assessed; five tumors were excluded from the analysis because of technical limitations. In the robotic arm, no antenna repositioning was required. In the freehand arm, a median of one repositioning was required (range, zero to seven repositionings; P < .001). For out-of-plane targets, lateral targeting error was 10.1 mm ± 4.0 and 5.9 mm ± 2.9 (P = .007) for freehand and robotic procedures, respectively, and for in-plane targets, lateral targeting error was 6.2 mm ± 2.7 and 7.7 mm ± 5.9, respectively (P = .51). Mean targeting time was 19 minutes (range, 8-55 minutes) and 36 minutes (range, 3-70 minutes; P = .001) for freehand and robotic procedures, respectively. Conclusion Robotic antenna guidance reduces the need for antenna repositioning in microwave ablation to accurately target liver tumors and increases accuracy for out-of-plane targets. However, targeting time was greater with robotic guidance than with freehand targeting. © RSNA, 2019.


Four Steps To My Future (4STMF): acceptability, feasibility and exploratory outcomes of a universal school-based mental health and well-being programme, delivered to young adolescents in South Africa.
Mental health disorders affect many children in South Africa, where vulnerability is high, and treatment is limited. We sought to determine the feasibility and acceptability of a universally delivered classroom-based programme for the promotion of mental health in young adolescents. We pilot tested an 8 session, cognitive-behavioural therapy-based programme, 4 Steps To My Future (4STMF) in two schools. Participants were grade 5 learners (n = 222; Meanage = 10.62 (Standard deviation = 0.69)). 4STMF was delivered in class time by trained psychology postgraduates. Feasibility (rates of parental opt-out, child assent, assessment completion at baseline and follow-up, programme completion, session attendance and programme fidelity), acceptability (teacher feedback and focus groups with learners), as well as demographic data and data on a battery of a psychological measures were collected at baseline, postintervention and at one-month follow-up. Most eligible learners at both schools agreed to participate (85% - school 1; 91% - school 2) with more than 80% completing postintervention measures. Learner session attendance and programme fidelity were high. Teachers rated facilitators highly on confidence, preparedness, enthusiasm and classroom management and observed children to be enjoying the programme. Focus group data suggest that learners liked the programme, could recall the content and had shared some of the content with their family. An exploratory analysis of outcomes showed significant pre-post differences on self-esteem at school 1 and on emotion regulation at school 1 and school 2, maintained at follow-up. This pilot study has shown that 4STMF can acceptably and feasibly be delivered, at classroom level, as a universal school-based prevention programme to young adolescent learners in South African primary schools. The programme could fit in with school context, could be delivered by nonspecialists, showed significant improvements on self-esteem and emotion regulation and was liked by the learners.


Safety Study of Single-Dose Intravenously Administered DOTA-Siglec-9 Peptide in Sprague Dawley Rats.
The peptide-based radioactive compound [68Ga]Ga-DOTA-Siglec-9 is a novel agent for imaging of inflammation with positron emission tomography. The drug target of [68Ga]Ga-DOTA-Siglec-9 is vascular adhesion protein 1. Previous studies have obtained promising results with [68Ga]Ga-DOTA-Siglec-9 in experimental animals. However, before taking this novel imaging agent into clinical trials, safety and toxicological studies need to be performed with the nonradioactive precursor compound DOTA-Siglec-9. This extended single-dose toxicity study was designed to provide information on the major toxic effects of DOTA-Siglec-9 and to indicate possible target organs after a single intravenous (iv) injection in rats. The study was performed using 60 adult Hsd: Sprague Dawley rats and included a control group and a treatment group to investigate the toxicity of DOTA-Siglec-9 solution at a final concentration of 0.2 mg/mL after a single iv injection of 582 µg/kg. The maximum dose tested was 1,000-fold the clinical dose on a mg/kg basis as indicated in European Medicines Agency International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guideline M3(R2). The planned human clinical dose is approximately 0.582 µg of DOTA-Siglec-9 per kg of body mass. This study demonstrates that iv administration of DOTA-Siglec-9 at a dose of 582 µg/kg was well tolerated in rats and did not produce toxicologically significant adverse effects.


A Phase I Trial of a Guadecitabine (SGI-110) and Irinotecan in Metastatic Colorectal Cancer Patients Previously Exposed to Irinotecan.
Chemotherapeutic resistance eventually develops in all patients with metastatic colorectal cancer (mCRC). Gene silencing through promoter demethylation is one potential reversible mechanism of resistance with administration of hypomethylating agents. We evaluated the safety and tolerability of guadecitabine and irinotecan in patients with mCRC previously treated with irinotecan. In this 3+3 dose-escalation study, patients with mCRC previously exposed to irinotecan received guadecitabine days 1 to 5 of a 28-day cycle and irinotecan 125 mg/m2 days 8 and 15 [dose level (DL) 1, guadecitabine 45 mg/m2; DL -1: guadecitabine 30 mg/m2; DL -1G: guadecitabine 30 mg/m2 with growth factor support (GFS); DL 1G: guadecitabine 45 mg/m2 with GFS]. Twenty-two patients were treated across four DLs. Dose-limiting toxicities were neutropenic fever (DL 1 and -1G), biliary drain infection (DL -1), colonic obstruction (DL -1), and severe dehydration (DL 1G). Most common toxicities were neutropenia (82% any grade, 77% Grade 3/4), neutropenic fever (23%), leukopenia (73% any grade, 50% Grade 3/4), and injection site reactions (64% total, 0% Grade 3/4). Patients received a median of 4.5 cycles of treatment; 12/17 evaluable patients had stable disease as best response, with one having initial disease progression but subsequently durable partial response. Circulating tumor DNA showed decrease in global demethylation by LINE-1 after treatment. We report the first study of chemo-priming with epigenetic therapy in gastrointestinal cancers. Guadecitabine 45 mg/m2 and irinotecan 125 mg/m2 with GFS was safe and tolerable in patients with mCRC, with early indication of benefit. These data have provided the basis for an ongoing phase II randomized, multicenter trial.


Soluble Fas and interleukin-6 and interleukin-8 levels in seminal plasma of infertile men.
The seminal plasma levels of soluble Fas (sFas) and interleukins IL-6 and IL-8 were measured and their relationship with semen qualities was examined. The seminal plasma sFas level in fertile males was significantly higher than that in the infertile group. On the other hand, seminal plasma level of IL-6 was significantly lower in fertile males than in the infertile group. In the infertile group, patients with oligozoospermia had a lower seminal plasma sFas and a higher IL-6 level than those with normal sperm concentration. There was an inverse correlation between IL-6 and sperm concentration in infertile patients. Seminal plasma IL-8 was not correlated with sperm parameters. It would appear that certain kinds of cytokine in the seminal plasma might play an important role in improving semen quality.


Two-dimensional variation of bursting properties in a silicon-neuron half-center oscillator.
We are developing hardware models of central pattern generators (CPGs) to enhance neural prostheses, create biologically based controllers for autonomous machines, and to better understand how biology creates stable and robust movements. Previously, we designed and implemented an analog integrated circuit model of a neuron with Hodgkin-Huxley like dynamics, the silicon neuron. In this work, we use silicon neurons to implement a half-center oscillator and show that the underlying dynamics of this CPG produce bursting behaviors that are well matched to the biological counterpart on which our model is based. In addition, we demonstrate the robustness of the bursting behavior by systematically varying two parameters in each silicon neuron and mapping the corresponding effects on the bursting.


Use of Erythropoietin in the Correction of Anemia in Pre-dialysis Patients.
Anemia is a well recognized complication of chronic renal failure (CRF). Although the use of erythropoietin (EPO) in the treatment of anemia in patients on dialysis is well established, its use in pre-dialysis patients is less well recognized. The preferred route of administration of EPO in pre-dialysis patients is subcutaneous and it is indicated in any patient with CRF who is symptomatic of anemia. Studies have shown that EPO is effective in correcting anemia in these patients with a considerable improvement in quality-of-life scores. There have been no deleterious effects on blood pressure or rate of decline of renal function. However, these two indices should be monitored closely. Common causes of treatment failure include iron deficiency, blood loss and occult sepsis. The available evidence indicates that EPO therapy is safe and effective in the treatment of anemia in pre-dialysis patients.


Anoplophorahuangjianbini sp. n. from Fujian and Guangxi, China (Coleoptera: Cerambycidae: Lamiinae).
The genus Anoplophora Hope, 1839 (Coleoptera: Cerambycidae: Lamiinae: Lamiini) includes 47 species (without subspecies) occurring in East, South and Southeast Asia. Amongst them, 38 species are known from CHINA. Members of this genus are familiar to Chinese people with a widely-used common name: " [starry longhorn beetle]". Anoplophora species have great economic importance, attacking and damaging numerous hardwood trees and some coniferous trees. A new species of starry longhorn beetle, Anoplophorahuangjianbini sp. n. (Coleoptera: Cerambycidae: Lamiinae: Lamiini) is described from Fujian and Guangxi, CHINA. Diagnostic characters of the new species are illustrated and comparison with closely-related congeners is provided.


Comparison between indirect immunofluorescence and microneutralization for detection of antibodies to polioviruses.
Indirect immunofluorescence and microneutralization methods for the detection of antibodies to poliovirus serotypes 1, 2, and 3 were compared. Of the 41 sera tested for poliovirus type 1 antibody, 40% were in complete agreement, 55% differed by one dilution, and 5% differed by two dilutions. For poliovirus type 2, 37 sera were tested; 56% completely agreed, and 44% differed by only one dilution. For poliovirus type 3, complete agreement occurred in 59% of 33 sera, while 41% differed by one dilution. No false-negative results were obtained. These findings suggest that indirect immunofluorescence for poliovirus types 1, 2, and 3 is as sensitive as the microneutralization method and could represent a less cumbersome alternative.


Traction and attraction: haptotaxis substrates collagen and fibronectin interact with chemotaxis by HGF to regulate myoblast migration in a microfluidic device.
Cell migration is central to development, wound healing, tissue regeneration, and immunity. Despite extensive knowledge of muscle regeneration, myoblast migration during regeneration is not well understood. C2C12 mouse myoblast migration and morphology were investigated using a triple-docking polydimethylsiloxane-based microfluidic device in which cells moved under gravity-driven laminar flow on uniform (=) collagen (CN=), fibronectin (FN=), or opposing gradients (CN-FN or FN-CN). In haptotaxis experiments, migration was faster on FN= than on CN=. At 10 h, cells were more elongated on FN-CN and migration was faster than on the CN-FN substrate. Net migration distance on FN-CN at 10 h was greater than on CN-FN, as cells rapidly entered the channel as a larger population (bulk-cell movement, wave 1). Hepatocyte growth factor (HGF) stimulated rapid chemotaxis on FN= but not CN=, increasing migration speed at 10 h early in the channel at low HGF in a steep HGF gradient. HGF accelerated migration on FN= and bulk-cell movement on both uniform substrates. An HGF gradient also slowed cells in wave 2 moving on FN-CN, not CN-FN. Both opposing-gradient substrates affected the shape, speed, and net distance of migrating cells. Gradient and uniform configurations of HGF and substrate differentially influenced migration behavior. Therefore, haptotaxis substrate configuration potently modifies myoblast chemotaxis by HGF. Innovative microfluidic experiments advance our understanding of intricate complexities of myoblast migration. Findings can be leveraged to engineer muscle-tissue volumes for transplantation after serious injury. New analytical approaches may generate broader insights into cell migration.


Minithoracotomy and Beating Heart Strategy for Mitral Surgery in Secondary Mitral Regurgitation.
In patients with secondary mitral regurgitation (MR) associated with low ejection fraction or previous heart surgery, minimally invasive mitral valve surgery without aortic cross-clamp (MIMVS-WAC) has shown promising results. We report our experience for this strategy in our centers. Between August 2011 and April 2017, 46 patients (mean age 69 ± 11 years, 76% males) received MIMVS-WAC. Indications for this technique were prior coronary bypass surgery (26%), severe or recent left ventricular (LV) dysfunction (30%), or both (39%). The mean EuroSCORE II was 12 ± 10. For each procedure, we conducted right minithoracotomy and hypothermic cardiopulmonary bypass (CPB) after peripheral cannulation. Mean CPB time was 159 ± 39 minutes. A mitral valve replacement (MVR) was performed in 23 cases (50%), an annuloplasty in 22 cases (48%), and a prosthesis pannus removal in 1 case (2%). Mean hospital length of stay was 12 ± 5.4 days. We report no sternotomy conversions, six reoperations for bleeding, and three deaths at 30 days. Transfusion was requested in 62% (mean infusion 2 ± 2.4 packed red blood cells). The postoperative echocardiography showed an LV function preservation in 69% of cases and a reduction of pulmonary arterial pressure in 73% of cases. Four additional deaths occurred in the long-term follow-up (mean 637 ± 381 days, median 593 days). No mitral reoperation was required, with a MR ≤ 2 in 90% of patients. In high-risk patients, the MIMVS-WAC is a safe technique. It avoids hard dissections while ensuring excellent preservation of cardiac function.


Nephrogenic adenoma: an update on an innocuous but troublesome entity.
Nephrogenic adenoma (NA) is a rare benign lesion of the urothelial tract that is typically preceded by some form of genitourinary insult. The pathogenesis of NA is not entirely clear. Although generally presumed to be a metaplastic process of the urothelium, recent evidence suggests that NA may in fact be derived from detached renal tubular cells implanting along the urothelial tract in previously injured areas, at least in cases associated with a kidney transplant. On light microscopy, NA shows a variety of patterns, including tubulocystic, papillary, and much less frequently solid, that often coexist. Recognition of its characteristic patterns, and awareness of its unusual architectural and cytologic features, is key to making the diagnosis of NA and distinguishing this lesion from malignant neoplasms occurring at the same sites, in particular, clear cell carcinoma, nested or microcystic variants of urothelial carcinoma and prostatic adenocarcinoma. Although straightforward in most cases, the correct diagnosis may be difficult to make on limited tissue samples. A number of immunohistochemical markers have been studied in an attempt to characterize NA; however, to date there is no specific immunohistochemical profile to distinguish this lesion from its malignant mimickers, although PAX2, a new marker, may prove to be helpful in this regard. Clinicopathologic correlation with careful attention to morphology remains the pillar in establishing the correct diagnosis.


[Number of nucleoli as an index of the proliferative activity of cells in vitro].
The number of nucleoli in cells is commonly insignificant (from 1 to 2). It may increase under numerous normal (regeneration) and pathological conditions. The data obtained suggest that activation of the nucleoli and the increase in the number cannot be specific characteristics of any pathological condition. Any disorders of tissue proliferative homeostasis will result in a change in the ratio of proliferative and resting cells and increase in the number of nucleoli.


Colostomy and ileostomy care in nursing education: Which is more effective: Synchronous or asynchronous?
To compare the effects of synchronous and asynchronous training on the academic achievements and e-learning attitudes of nursing student trained in colostomy and ileostomy care. The quasi-experimental, descriptive study was conducted at the Nursing Department of a health facility after approval from the Tekirdag Namik Kemal University, Tekirdag, Turkey, from May to June 2020, and comprised nursing students who were divided in intervention group A and control group B. Those in group A were given synchronous training on colostomy and ileostomy care using active learning techniques on an online platform, while those group B received their training only asynchronously. Data was collected using Colostomy and Ileostomy Knowledge Test, and the e-Learning Attitude Scale at baseline and post-intervention. Data was analysed using SPSS 17. Of the 154 students, there were 77(50%) in each of the two groups. Overall, 53(34.4%) students were in 2nd grade, 60(39%) in 3rd, and 41(26.6%) in 4th grade of their training. The mean age of the sample was 21.50±1.10 years. Post-intervention mean scores for knowledge and e-learning tendency were significantly higher in both the groups compared to the baseline (p<0.01). Mean score for e-learning avoidance was significantly lower and mean knowledge score was significantly higher in group A than group B (p<0.05). The application of active learning activities among students was found to have a positive effect on nursing education compared to asynchronous teaching.


A reduction in selective immune pressure during the course of chronic hepatitis C correlates with diminished biochemical evidence of hepatic inflammation.
It is considered that selection pressure exerted by the host immune response during early HCV infection might influence the outcome of that infection particularly as it relates to persistence or clearance of the agent. However, it is unclear whether positive selection pressure plays a role in determining the severity of hepatitis C during the course of persistent HCV infection. To address the evolutionary mechanism by which HCV escapes from the host immune response and to assess the relationship between viral evolution and hepatic inflammation, we determined 57 sequences (3-5 serial samples per patient) from 5 individuals with persistent HCV infection of genotype 1a who were under long-term follow-up ranging from 15.6 to 21.6 years. We applied a novel method to estimate serial alternations of selective pressure against the HCV enveloped region and compared this to fluctuation in transaminase level over time. Positive selection pressure was reduced over time postinfection, as evidenced by a reduction in nonsynonymous substitutions in the later phase of infection. Furthermore, serum transaminase, as a measure of inflammatory necrosis of hepatocytes, was reduced in parallel with decreased positive selection pressure. These results suggest that during persistent HCV infection, the virus faces diminished immune pressure over time, either from mutation to an immune resistant sequence or from immunologic exhaustion, and that this diminished immune attack is reflected in diminished inflammatory activity. This observation may be applicable to other viruses characterized by a slow rate of disease progression.


Microbial metagenome profiling using amplicon length heterogeneity-polymerase chain reaction proves more effective than elemental analysis in discriminating soil specimens.
The combination of soil's ubiquity and its intrinsic abiotic and biotic information can contribute greatly to the forensic field. Although there are physical and chemical characterization methods of soil comparison for forensic purposes, these require a level of expertise not always encountered in crime laboratories. We hypothesized that soil microbial community profiling could be used to discriminate between soil types by providing biological fingerprints that confer uniqueness. Three of the six Miami-Dade soil types were randomly selected and sampled. We compared the microbial metagenome profiles generated using amplicon length heterogeneity-polymerase chain reaction analysis of the 16S rRNA genes with inductively coupled plasma optical emission spectroscopy analysis of 13 elements (Al, B, Ca, Cu, Fe, K, Mg, Mn, Na, P, S, Si, and Zn) that are commonly encountered in soils. Bray-Curtis similarity index and analysis of similarity were performed on all data to establish differences within sites, among sites, and across two seasons. These data matrices were used to group samples that shared similar community patterns using nonmetric multidimensional scaling analysis. We concluded that while chemical characterization could provide some differentiation between soils, microbial metagenome profiling was better able to discriminate between the soil types and had a high degree of reproducibility, therefore proving to be a potential tool for forensic soil comparisons.


Operational Insights From the Longitudinal Analysis of a Linear Accelerator Machine Log.
Purpose This study aimed to perform a longitudinal analysis of linear accelerator (linac) technical faults reported with a cloud-based Machine Log system in use in a busy academic clinic and derive operational insights related to linac reliability, clinical utilization, and performance. Methods We queried the Machine Log system for the following parameters: linac type, number of reported technical faults, types of fault, number of faults where the linac was disabled, and estimated clinical downtime. The number of fractions treated and monitor units (MU) delivered were obtained from the record and verify system as metrics of linac utilization and to normalize the number of reported linac faults, facilitating inter-comparison. Two Varian TrueBeam C-arm linacs (Varian Medical Systems, Palo Alto, CA), one Varian 21iX C-arm linac (Varian Medical Systems, Palo Alto, CA), and one newly installed Varian Halcyon ring gantry linac (Varian Medical Systems, Palo Alto, CA) were evaluated. The linacs were studied over a 30-month period from September 2017 to March 2020. Results Over 30 months, comprising 677 clinical days, 1234 faults were reported from all linacs, including 153 "linac down" events requiring rescheduling or cancellation of treatments. The TrueBeam linacs reported nearly twice as many imaging, multileaf collimator (MLC), and beam generation faults per fraction, and MU as the Halcyon. Halcyon experienced fewer beam generation/steering, accessory, and cooling-related faults than the other linacs but reported more computer and networking issues. Although it employs a relatively new MLC design compared to the C-arm linacs and delivers primarily intensity-modulated treatments, Halcyon reported fewer MLC faults than the other linacs. The 21iX linac had the fewest software-related faults but was subject to the most cooling-related faults, which we attributed to extensive use of this linac for treatment techniques with extended beam-on times. Conclusions A longitudinal analysis of a cloud-based Machine Log system yielded operational insights into the utilization, performance, and technical reliability of the linacs in use at our institution. Several trends in linac sub-system reliability were identified and could be attributed to either age, design, clinical use, or operational demands. The results of this analysis will be used as a basis for designing linac quality assurance schedules that reflect actual linac usage and observed sub-system reliability. Such a practice may contribute to a clinic workflow subject to fewer disruptions from linac faults, ultimately improving efficiency and patient safety.


[Abdominal presentation of B-cell non-Hodgkin's lymphoma (B-NHL) - surgical treatment and its results. Report of the Polish Paediatric Leukaemia/Lymphoma Study Group].
The aim of this study was to analyse the effect of LMB-89 protocol and surgical procedure at initial laparotomy on the outcome in children with abdominal B-cell NHL. The initial surgery intervention was: complete resection (20% pts), subtotal resection (20%), partial resection (4%), biopsy (36%). Postoperative complications occurred in 5 children. Complete recovery (CR) was achieved in 92% pts. There were 4% non responder patients. Two patients died before CR evaluation (tumour lysis syndrome; bleeding and multi organ failure after initial surgery). One patient died in CCR from sepsis probably influenced by the previous local operation. 10.8% patients relapsed. The estimate EFS for all patients with AB-NHL is 81%, 85% for stage III and 73% for stage IV. Major surgery in advanced stages is not recommended since it delays chemotherapy and fails to improve overall survival.


The false-positive rate of thoracic outlet syndrome shoulder maneuvers in healthy subjects.
To estimate the incidence of false-positive findings of thoracic outlet syndrome (TOS) shoulder maneuvers, Adson's test (AT), costoclavicular maneuver (CCM), elevated arm stress test (EAST), and supraclavicular pressure (SCP) in healthy subjects. A cross-sectional, observational study was performed in a medical school and affiliated emergency medicine residency program setting. Participants included healthy adult volunteers without symptoms of TOS. The shoulder maneuvers AT, CCM, EAST, and SCP were performed in randomized order for 30 sec, 30 sec, 3 min, and 30 sec, respectively. Pulse quality and the presence and timing of pain or paresthesias were assessed. 53 subjects were enrolled, including 27 women, aged 29.7 +/- 6.4 years (range 21-58 years). AT, CCM, EAST, and SCP resulted in an altered pulse in 11%, 11%, 62%, and 21%; pain in 0%, 0%, 21%, and 2%; and paresthesias in 11%, 15%, 36%, and 15% of cases, respectively. The following outcomes had reasonable false-positive rates (upper 95% confidence limit): pain with the AT (7%), CCM (7%), SCP (10%), or any 2 TOS shoulder maneuvers (10%); discontinuing the EAST because of symptoms (16%); or any symptom with 3 (13%) or 4 (7%) TOS shoulder maneuvers. In a study of TOS shoulder maneuvers in healthy subjects, the outcomes of pulse alteration or paresthesias were unreliable in general. However, TOS shoulder maneuvers have reasonably low false-positive rates when a positive outcome is defined as pain after AT, CCM, or SCP; discontinuation of the EAST secondary to pain; pain in the same arm with > or =2 maneuvers; or any symptom in the same arm with > or =3 maneuvers.


Current practice and potential strategy in diagnosing COVID-19.
To summarize the current practice and potential strategy in diagnosing coronavirus disease 2019 (COVID-19). PubMed, Web of Science were systematically searched using terms including "COVID-19", "SARS-CoV-2" and "2019-nCoV". After removing duplicates, we then identified articles, letters and commentaries regarding diagnosing COVID-19. Here we summarized relatively mature diagnostic methods like nuclear acid test and computed tomography. Besides, new aspects regarding these detection methods like suitable specimens for nuclear acid test, possible use of 18F-FDG PET/CT were also reported. Especially, we also presented several novel techniques for diagnosing COVID-19 like lung ultrasound. Chinese Clinical Guidance for COVID-19 Pneumonia Diagnosis and Treatment (7th edition) by National Health Commission is recommended to follow as it provides detailed diagnostic procedures using currently available tools. We suggest clinicians further explore the saliva's utility as a specimen for nuclear acid test and the use of lung ultrasound.


[Clinical profile and results of acute pancreatitis in the Intensive and Intermediate Care Unit of a general hospital].
Intraductal papillary mucinous neoplasms (IPMN) are diagnosed more frequently because the higher use of radiologic exams, in that sense they are a great challenge to define its management and treatment in relation to its potential malignant transformation. To describe IPMN clinical profile, endoscopic ultrasound (EUS) characteristics and survival in all patients diagnosed with IPMN by EUS at HNERM. Retrospective cohort of patients with IPMN diagnosed at HNERM by EUS from 2013 to 2018. Descriptive statistics was used for clinical profile and EUS characteristics. Kaplan Meir Method and Cox regression analysis was applied for survival analysis. 133 patients with IPMN were included. Medium age was 68.6 years, 80 (60.2%) were female. According to IPMN subtypes, 89 (66.9%) originated from secondary branch, 23 (17.3%) from main duct (MD) and 21 (15.8%) were mixed type (MT). Head of pancreas was the main localization (41.4%). In follow-up, 22 (16.5%) were derived to surgery. Mortality occurred in 16.5% (22 cases) after a median follow-up of 522 days. Malignant transformation was diagnosed in 6% (8 cases). Survival was 86.8% (IC 95%, 79.6-91.6) at 1 year and 81.9% (IC95%, 73.3-88.0) at 3 years. Univariate analysis demonstrated that factors associated to survival were MD-IPMN (p=0.02) y MT-IPMN (p=0.005), male gender (p=004), nodule size ≥30 mm (p=0.000), presence of nodules (p=0.014) and Wirsung ≥10 mm (p=0.01). Multivariate analysis showed that predictive factors for survival were MD-IPMN (HR=6.3, p=0.005), MT-IPMN (HR=4.9, p=0.008) and nodule size ≥30 mm (HR=7.1, p=0.000). Diagnosis of MD-IPMN and MT-IPMN are predictive factors for survival as well as nodule size ≥ 30mm.


Assessment of microwave-assisted enzymatic digestion by measuring glycated hemoglobin A1c by mass spectrometry.
Enzymatic digestion of proteins and analysis of the resulting peptides by mass spectrometry is an established approach in proteomics and in clinical and environmental chemistry. The long digestion times of several hours prevent the fast turnover of samples and results. Qualitative applications showed that microwave radiation profoundly shortens enzymatic digestion. However, its usefulness for quantitative applications had not been assessed. In this study, the microwave-assisted enzymatic digestion of hemoglobin at different temperatures, buffer concentrations, and digestion times was assessed and compared with conventional digestion for the proteolytic enzymes trypsin and Glu-C. A microwave-assisted enzymatic digestion method optimized for digestion time and temperature was applied for the analysis of glycated hemoglobin HbA1c and compared with a reference method. Using trypsin, complete digestion was obtained at 50 degrees C within 20 min. Under these conditions, the digestion efficiency was 20% higher than with conventional trypsin digestion. These effects were not observed with Glu-C as enzyme, probably because of the decreased stability of Glu-C at elevated temperatures in comparison with the trypsin used. The comparison of the optimized microwave-assisted digestion method using trypsin with the reference method for HbA1c using Glu-C gave a close correlation in the results (R2: 0.996). A significant bias of 0.33% HbA1c was observed, with higher values obtained with the microwave-assisted tryptic digest; this finding might have resulted from the use of a different enzyme. This study showed that microwave-assisted enzymatic digestion can substantially reduce digestion times to minutes and can be used in qualitative as well as quantitative applications.


Comparison of genotypic and phenotypic HIV type 1 tropism assay: results from the screening samples of Cenicriviroc Study 202, a randomized phase II trial in treatment-naive subjects.
Cenicriviroc is a once-daily oral CCR5/CCR2 antagonist in development for treatment of HIV infection. CVC Study 202 (652-2-202; NCT01338883) excluded treatment-naive subjects demonstrated to harbor non-R5 (CXCR4-tropic or dual-mixed) tropic HIV-1 by either genotypic or phenotypic tropism testing. Here we compare the results of genotypic and phenotypic tropism testing in Study 202. A total of 304 subjects screened had paired genotypic and phenotypic results. Genotypic tropism testing (GTT) incorporated triplicate population sequencing using the geno2pheno algorithm and the PSSM algorithm, followed by ultradeep sequencing (UDS) for samples with R5 results. All samples were further evaluated with a phenotypic test, the enhanced-sensitivity Trofile assay (ESTA). Concordance between GTT and ESTA was 80% and increased to 84% when only geno2pheno was used for triplicate population sequencing. GTT (geno2pheno) classified 18% of the samples as non-R5 compared to 16% by ESTA. Only one-third of samples with non-R5 results by either test were classified as non-R5 by both tests. Median CD4((+)) cell counts were lower in patients with concordant non-R5 results by UDS and ESTA than in subjects with an R5 result by either assay (p=0.0004). UDS detected non-R5 virus in an additional 27/304 subjects (median 15% non-R5, interquartile range: 3.7-62%) with R5 results by ESTA. In conclusion, the geno2pheno algorithm improves concordance of GTT with a clinically validated phenotypic tropism assay as does the use of UDS. These findings provide support for recent guidelines indicating that genotypic tropism testing may be considered as an alternative to phenotypic testing.


Patient acceptance of fetal monitoring as a helpful tool.
In 1972, 50 women on a postpartum unit were interviewed to investigate responses to fetal monitoring. Not one woman interviewed had a positive initial response; 31 women had negative initial responses. In 1977, in a replication of the study, 11 women had positive initial responses, 11 had negative initial responses, and 28 had neutral initial responses. Two significant findings: 1) older women initially reacted more positively to fetal monitoring than younger women; and 2) married women initially reacted more positively to fetal monitoring than single women. This indicates a need for nurses to be more sensitive to young, single women's initial responses to fetal monitoring. In the 1977 study subsequent responses were 37 positive, 4 negative, and 9 neutral.


[New trends in the treatment of hemodynamic disorders in liver cirrhosis].
The paper reviews literature data available and first-hand experience in relation to hemodynamics of portal blood flow, lesser and greater circulation in patients with chronic diffuse hepatic diseases. Relevance of circulatory changes to hepatic lesions is also considered. With regard to specific features of hemodynamic disturbances in hepatic lesions it is suggested to use cardiovascular drugs. A pharmacodynamic effect is compared for beta-adrenoblockers, calcium antagonists and nitrates administered to patients with affected hepatobiliary system.


Assessment of the geographic origins of pinewood nematode isolates via single nucleotide polymorphism in effector genes.
The pinewood nematode, Bursaphelenchus xylophilus, is native to North America but it only causes damaging pine wilt disease in those regions of the world where it has been introduced. The accurate detection of the species and its dispersal routes are thus essential to define effective control measures. The main goals of this study were to analyse the genetic diversity among B. xylophilus isolates from different geographic locations and identify single nucleotide polymorphism (SNPs) markers for geographic origin, through a comparative transcriptomic approach. The transcriptomes of seven B. xylophilus isolates, from Continental Portugal (4), China (1), Japan (1) and USA (1), were sequenced in the next generation platform Roche 454. Analysis of effector gene transcripts revealed inter-isolate nucleotide diversity that was validated by Sanger sequencing in the genomic DNA of the seven isolates and eight additional isolates from different geographic locations: Madeira Island (2), China (1), USA (1), Japan (2) and South Korea (2). The analysis identified 136 polymorphic positions in 10 effector transcripts. Pairwise comparison of the 136 SNPs through Neighbor-Joining and the Maximum Likelihood methods and 5-mer frequency analysis with the alignment-independent bilinear multivariate modelling approach correlated the SNPs with the isolates geographic origin. Furthermore, the SNP analysis indicated a closer proximity of the Portuguese isolates to the Korean and Chinese isolates than to the Japanese or American isolates. Each geographic cluster carried exclusive alleles that can be used as SNP markers for B. xylophilus isolate identification.


[A voluminous foraminal and extra foraminal disk hernia mimicking a tumor].
In some cases, disc herniation can be voluminous and can then constitute a differential diagnosis with tumours. We report the case of a 46 years-old female with sciatica and crural neuralgia which resisted to medical treatment. X-rays exams were normal, but the computerized tomography showed a voluminous mass in contact with the L5 nervous root and which was developed in the psoas major muscle. The MRI revealed a voluminous foraminal and extra foraminal herniation at the L4-L5 vertebral disc, extended up to the psoas major muscle and associated with an important inflammatory infiltration. Surgical treatment was successful with a follow up of 8 months.


Technical note: Digital quantification of eye pigmentation of cattle with white faces.
Cancer of the eye in cattle with white faces occurs less frequently in cattle with pigmented eyelids. Corneoscleral pigmentation is related to eyelid pigmentation and occurrence of lesions that may precede cancer. Objectives of this study were to assess 1) variation in the proportion of eyelid and corneoscleral pigmentation in Hereford, Bos taurus, and Bos indicus crossbreds and 2) the occurrence of lesions with the presence of pigmentation in those areas. Hereford and Bos indicus crosses (Brahman or Nellore with Angus and Hereford and straightbred Brafords) and Bos taurus crosses (Angus-Hereford) were included in the study (n = 1,083). Eyelid pigmentation proportions were estimated by pixel quantification and were evaluated as total proportions and for upper and lower eyelids distinctly for each eye. Fixed effects included breed type, age categories, and sex of the animal. Lesion presence (1) or absence (0) was obtained by visual appraisal of image and was assumed to be binomially distributed. Eyelid pigmentation proportions (overall, upper, and lower eyelids) for Hereford ranged from 0.65 ± 0.03 to 0.68 ± 0.03 and were significantly lower than Bos indicus (range from 0.93 ± 0.02 to 0.95 ± 0.02) or Bos taurus (ranged from 0.88 ± 0.02 to 0.92 ± 0.02) crosses. Corneoscleral pigmentation in Hereford cows (0.17 ± 0.06) did not differ (P = 0.91) from Hereford calves and yearlings (0.16 ± 0.07). Bos indicus and Bos taurus crossbred cows had larger corneoscleral pigmentation (0.38 ± 0.05 and 0.48 ± 0.04 for left eyes and 0.37 ± 0.05 and 0.53 ± 0.04 for right eyes, respectively) than all calves (P < 0.001), and their corneoscleral pigmentations were greater than that of Hereford cows (P < 0.003). Bos indicus and Bos taurus cows had greater proportions of left eye corneoscleral pigmentation (0.38 ± 0.05 and 0.48 ± 0.04, respectively) than Hereford cows (0.17 ± 0.06) and all young animal breed types (P < 0.05). Right eye proportions differed for all cow groups (P < 0.05; 0.53 ± 0.04, 0.37 ± 0.05, and 0.17 ± 0.06). Among calves and yearlings, Hereford had a lower right eye corneoscleral pigmentation proportion (0.16 ± 0.07) than Bos taurus (P = 0.02). The lesion proportion for Hereford (0.08 ± 0.03) was significantly greater than that of either Bos indicus (0.01 ± 0.005) or Bos taurus (0.01 ± 0.003). Crossbreeding with Bos taurus or Bos indicus animals appears to increase eye pigmentation, which may help reduce the occurrence of cancer in eyes of cattle with white faces.


The dry season in haiti: a window of opportunity to eliminate cholera.
Since the beginning of the cholera epidemic in Haiti, attack rates have varied drastically with alternating peak and lull phases, which were partly associated with the fluctuating dry, rainy and cyclonic seasons. According to a study conducted in 2012, the toxigenic V. cholerae O1 strain responsible for the outbreak did not settle at a significant level in the Haitian aquatic environment. Therefore, we hypothesize that some areas of lingering cholera transmission during the dry season could play an important role in the re-emergence of outbreaks during the rainy season. Our objective was therefore to describe the dynamics of cholera and assess the fight against the disease during the dry season. A field study was conducted from February 19 to March 29, 2013. After identifying the affected communes by analyzing the national cholera database, we visited corresponding health facilities to identify patient origins. We then conducted a field assessment of these foci to confirm the presence of cholera, assess factors associated with transmission and examine the activities implemented to control the epidemic since the beginning of the current dry season. We found that the great majority of Haitian communes (109/140) presented no sign of cholera transmission in February and March 2013. Suspected cases were concentrated in a small number of urban and rural areas, almost all of which were located in the northern half of the country and often in inland locales. In these areas, community health activities appeared insufficient and were often inappropriately targeted. Out of 49 analyzed foci, only 10 had benefited from at least one intervention involving the distribution of water treatment products together with an awareness campaign since December 2012. Cholera continues to affect Haiti as observed in early 2013; however, activities implemented to interrupt cholera transmission appear insufficient and poorly suited. This deficiency in the fight against cholera, especially at a period when transmission is weak, may explain the persistence of cholera even in the absence of significant aquatic reservoirs in Haiti.


The Relationship between Alcohol Consumption and other Risk Factors Assessed Using An Ongoing Population-based Surveillance System.
The aim of this study was to determine the relationship of alcohol consumption (reported in four different ways) with other specific disease-related risk factors (that is, smoking, high body mass index, low physical activity and insufficient fruit and vegetables). Data were collected from 2003 to 2015 in South Australia using an on-going monthly chronic disease and risk factor telephone survey of randomly selected persons (18+ years). The proportion of alcohol drinkers and, for those who drank alcohol, the proportion drinking more than one day per week, the proportion drinking on six or more days per week, and the mean alcohol drinks per day were assessed. Logistic regression and linear regression modelling were used on age and sex adjusted data. In total, over 71,000 respondents aged 18 years and older were interviewed (48.8% male). Overall prevalence of alcohol consumption was 81.3%. Trends in the direction promoted by current policies and preventative authorities were apparent with appropriate changes for all four measures for overall and for those underweight, undertaking sufficient activity, consuming <2 serves of fruit per day, consuming <5 serves of vegetables per day and with 3+ total risk factors. This research has provided evidence on the trends in alcohol consumption in relation to a range of other specific modifiable disease-related risk factors. The trends analysis has shown different patterns for each risk factor, and highlights the interplay between the respective modifiable or preventive risk factors.


Bi-frontal transcranial alternating current stimulation in the ripple range reduced overnight forgetting.
High frequency oscillations in the hippocampal structures recorded during sleep have been proved to be essential for long-term episodic memory consolidation in both animals and in humans. The aim of this study was to test if transcranial Alternating Current Stimulation (tACS) of the dorsolateral prefrontal cortex (DLPFC) in the hippocampal ripple range, applied bi-frontally during encoding, could modulate declarative memory performance, measured immediately after encoding, and after a night's sleep. An associative word-pair learning test was used. During an evening encoding phase, participants received 1 mA 140 Hz tACS or sham stimulation over both DLPFCs for 10 min while being presented twice with a list of word-pairs. Cued recall performance was investigated 10 min after training and the morning following the training session. Forgetting from evening to morning was observed in the sham condition, but not in the 140 Hz stimulation condition. 140 Hz tACS during encoding may have an effect on the consolidation of declarative material.


Does mid-luteal progesterone predict pregnancy in intrauterine insemination cycles following sequential clomiphene citrate and gonadotropin treatment?
This study aimed to determine whether serum mid-luteal progesterone (MLP) levels measured in the current treatment cycles of infertile women undergoing controlled ovarian hyperstimulation and intrauterine insemination following the sequential use of clomiphene citrate and gonadotropin may predict pregnancy. A total of 107 consecutive anovulatory women were included in this prospective cohort study. Patients with other causes of infertility were also excluded from the study. None of the patients received progesterone treatment for luteal phase support. The data recorded for each woman included age, body mass index, infertility type and duration, basal hormone levels, and previous and current cycle characteristics with MLP levels. Ovulation was confirmed using MLP and sonographic evaluation in all patients. An MLP level of > 3 ng/mL was regarded as a sign of ovulation. After treatment, the patients were divided into 2 groups according to the presence or absence of pregnancy, and the obtained data were compared between the groups. There were no significant differences in age, body mass index, or basal hormone levels between the 2 groups (all P > .05). However, the duration of infertility was significantly shorter in the pregnancy group (P = .003). The anovulation rate in this cohort was 18.7% (n = 20). A total of 15 (14%) were examined. MLP levels were 25.1 ± 13.8 ng/mL and 18.3 ± 14.5 ng/mL in the pregnant and nonpregnant groups, respectively (P:.089). Based on the receiver operating characteristic curve analysis, it was determined that there was no predictive value of the mid-luteal phase progesterone level for pregnancy in patients in whom ovulation was detected. Mid-luteal serum progesterone levels did not predict pregnancy in infertile women who underwent controlled ovarian hyperstimulation with sequential clomiphene citrate plus gonadotropin treatment and intrauterine insemination.


Endotoxin impairs biliary glutathione and HCO3- excretion and blocks the choleretic effect of nitric oxide in rat liver.
Cholestasis in patients with sepsis has been attributed to the effects of endotoxin (lipopolysaccharides, LPS) and LPS-induced cytokines, which are also potent stimulators of systemic and hepatic nitric oxide (NO) synthesis. NO donors stimulate bile acid-independent bile flow in normal rat liver, but the effects of LPS-induced NO on bile formation remain unclear. To address this question we examined the effects of NO and its mediator guanosine 3',5'-cyclic monophosphate (cGMP) on bile flow and biliary HCO3- and glutathione excretion in isolated perfused rat livers (IPRL) from LPS-treated rats. Portal and systemic NO2- + NO3- plasma levels were increased 47-fold in LPS-treated rats and were also elevated in perfusate (6-fold) and bile (9-fold) after isolating and perfusing livers from these animals. Bile flow, HCO3-, and glutathione output were decreased by 33%, 25%, and 81% in these IPRL, respectively. Stimulation of NO synthesis with L-arginine or inhibition of inducible NO synthesis with aminoguanidine did not change bile flow, although pretreatment with aminoguanidine inhibited NO production by 85%. Moreover, the choleretic effects of infusions of the NO donors sodium nitroprusside (SNP) and S-nitroso-acetyl-penicillamine were markedly reduced in endotoxemic IPRL compared with normal controls, and SNP-induced HCO3- and glutathione excretion were reduced by 61% and 86%, respectively. SNP-induced cyclic GMP production was 2.3-fold lower than in normals, but the choleretic effect of dibutyryl cGMP was only slightly reduced in endotoxemic livers. These findings indicate that LPS reduces bile acid-independent bile flow primarily by inhibiting biliary excretion of glutathione and to a lesser extent HCO3-, whereas LPS-induced NO does not modulate bile formation in endotoxemia. Thus, impairment of the major determinants of bile acid-independent bile flow by LPS may contribute significantly to the pathogenesis of the cholestasis of sepsis.


The effect of Replens on vaginal cytology in the treatment of postmenopausal atrophy: cytomorphology versus computerised cytometry.
After the menopause decreased concentrations of oestrogen may result in insufficient maturation of the vaginal epithelium, which can lead to a range of vaginal discomforts. This state of vaginal atrophy may be treated with oestrogen replacement treatment. Replens, a non-hormonal alternative to oestrogen replacement treatment has been shown to be effective in relieving symptoms related to vaginal atrophy in previous studies. To study the effect of Replens on the maturation of the vaginal epithelium and morphology of the vaginal cells and to compare the results of a recently developed cytomorphometric method with manual assessment of the degree of maturation in vaginal smears. Vaginal smears from 38 postmenopausal women suffering from symptoms related to vaginal atrophy were analysed manually and by cytomorphometry. The maturation value (MV) and the percentages of (para)basal, intermediate, and superficial cells (maturation index; MI) were measured by both methods before and after treatment with Replens. Cytomorphometry also measured mean cellular area, mean nuclear area, and mean area ratio. A correlation was shown between the two methods in the assessment of percentages of (para) basal and intermediate cells and MV. Cytomorphometric data showed a significant increase in mean cellular area, indicating a positive effect of Replens on the maturation of the vaginal epithelium. Changes in nuclear area and ratio between nuclear and cellular areas were not significant. Treatment with Replens did not influence MI or MV, as assessed by the two methods. Replens did have an effect on vaginal morphology. The automated procedure may be useful for the assessment of maturation in vaginal smears and is more sensitive to small (subvisual) changes.


Defining chaos.
In this paper, we propose, discuss, and illustrate a computationally feasible definition of chaos which can be applied very generally to situations that are commonly encountered, including attractors, repellers, and non-periodically forced systems. This definition is based on an entropy-like quantity, which we call "expansion entropy," and we define chaos as occurring when this quantity is positive. We relate and compare expansion entropy to the well-known concept of topological entropy to which it is equivalent under appropriate conditions. We also present example illustrations, discuss computational implementations, and point out issues arising from attempts at giving definitions of chaos that are not entropy-based.


Association between severity of dental caries and the risk of stroke.
The relationship between dental caries and stroke remains inconclusive. The aim of this study is to investigate whether different severities of dental caries affect the risk of stroke. This retrospective cohort study was conducted using the 2000-2013 Taiwan National Health Insurance Database. We selected 23,662 patients with advanced/severe dental caries and 23,662 patients with incipient/moderate dental caries between 2000 and 2006. These patients were followed to the occurrence of stroke or to the end of the study in 2013. Hazard ratios (HRs) and 95% confidence intervals (CIs) derived from the Cox proportional hazards models were calculated to assess the association between severity of dental caries and the risk of stroke. The advanced/severe dental caries group had a significantly higher risk of stroke compared with incipient/moderate dental caries group (adjusted HR, 1.16; 95% CI, 1.03-1.31). Stratified analyses showed that advanced/severe dental caries was positively associated with the risk of ischemic stroke in patients aged ≥40 years and with the risk of hemorrhagic stroke in patients aged <40 years. There is a severity-dependent association between dental caries and stroke in an Asian population.


Integrated Analysis of Transcriptomics and Metabolomics Unveil the Novel Insight of One-Year-Old Precocious Mechanism in the Chinese Mitten Crab, Eriocheir sinensis.
Eriocheir sinensis is traditionally a native high-value crab that is widely distributed in eastern Asia, and the precocity is considered the bottleneck problem affecting the development of the industry. The precocious E. sinensis is defined as a crab that reaches complete sexual maturation during the first year of its lifespan rather than as normally in the second year. However, the exact regulatory mechanisms underlying the precocity are still unclear to date. This study is the first to explore the mechanism of precocity with transcriptome-metabolome association analysis between the precocious and normal sexually mature E. sinensis. Our results indicated that the phenylalanine metabolism (map00360) and neuroactive ligand-receptor interaction (map04080) pathways play an important role in the precocity in the ovary of E. sinensis. In map00360, the predicted aromatic-L-amino-acid decarboxylase and 4-hydroxyphenylpyruvate dioxygenase isoform X1 genes and the phenethylamine, phenylethyl alcohol, trans-2-hydroxycinnamate, and L-tyrosine metabolites were all down-regulated in the ovary of the precocious E. sinensis. The map04080 was the common KEGG pathway in the ovary and hepatopancreas between the precocious and normal crab. In the ovary, the predicted growth hormone secretagogue receptor type 1 gene was up-regulated, and the L-glutamate metabolite was down-regulated in the precocious E. sinensis. In the hepatopancreas, the predicted forkhead box protein I2 gene and taurine metabolite were up-regulated and the the L-glutamate metabolite was down-regulated in the precocious crab. There was no common pathway in the testis. Numerous common pathways in the hepatopancreas between male precocious and normal crab were identified. The specific amino acids, fatty acids and flavorful nucleotide (inosine monophosphate (MP), cytidine MP, adenosine MP, uridine MP, and guanosine MP) contents in the hepatopancreas and gonads further confirmed the above omics results. Our results suggest that the phenylalanine metabolism may affect the ovarian development by changing the contents of the neurotransmitter and tyrosine. The neuroactive ligand-receptor interaction pathway may affect the growth by changing the expressions of related genes and affect the umami taste of the gonads and hepatopancreas through the differences of L-glutamate metabolite in the precocious E. sinensis. The results provided valuable and novel insights on the precocious mechanism and may have a significant impact on the development of the E. sinensis aquaculture industry.


Diagnosis and management of pre-eclampsia: an update.
Pre-eclampsia is a significant, multifactorial, multiorgan disease affecting 5%-8% of all pregnancies in the US where it is the third leading cause of maternal mortality. Despite improvements in the diagnosis and management of pre-eclampsia, severe complications can occur in both the mother and the fetus, and there is no effective method of prevention. Early detection and identification of pregnant women most at risk of developing the disease have proven challenging, but recent efforts combining biochemical and biophysical markers are promising. Efforts at prevention of pre-eclampsia with aspirin and calcium have had limited success, but research on modifiable risk factors, such as obesity surgery, are encouraging. Obstetric management of severe pre-eclampsia focuses on medical management of blood pressure and prevention of seizures using magnesium sulfate, but the ultimate cure remains delivery of the fetus and placenta. Timing of delivery depends on several factors, including gestational age, fetal lung maturity, and most importantly, disease severity. Anesthetic management includes regional anesthesia with careful evaluation of the patient's airway, volume status, and coagulation status to reduce morbidity and mortality. The potential complications of general anesthesia, including intracranial hemorrhage, in these patients make regional anesthesia the preferred choice in many cases. Nevertheless, it is important to be aware of the contraindications to neuraxial anesthesia and to prepare always for the possibility of encountering a difficult airway.


Modeling Neurodegenerative Disorders in Drosophila melanogaster.
Drosophila melanogaster provides a powerful genetic model system in which to investigate the molecular mechanisms underlying neurodegenerative diseases. In this review, we discuss recent progress in Drosophila modeling Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis (ALS), Huntington's Disease, Ataxia Telangiectasia, and neurodegeneration related to mitochondrial dysfunction or traumatic brain injury. We close by discussing recent progress using Drosophila models of neural regeneration and how these are likely to provide critical insights into future treatments for neurodegenerative disorders.


Aqueous hafnium sulfate chemistry: structures of crystalline precipitates.
Crystalline precipitates resulting from the hydrolysis and subsequent condensation of Hf(IV) aqueous acidic solutions at 60-95 °C are examined and compared. By varying the concentrations of the acid and sulfate source, a variety of complex hafnium-oxo-hydroxo-sulfate clusters are isolated and structures accessed. Four novel compounds were discovered, while the structures of two known compounds, an 18-mer and a planar hexamer, were updated. In total, the compounds described herein each contain one of four cluster architectures: 18-mer, 11-mer, nonamer, and planar hexamer. In addition, one compound contains small amounts of 19-mers together with 18-mers. As well as examining the individual structure of each complex cluster, we relate them to one another, as well as to the dense phases of HfO2, to gain an understanding of their formation and stability. Finally, the solution conditions under which each cluster forms are identified by plotting the crystallization regions of each cluster against acidity and sulfate concentration. Most clusters form under slightly acidic conditions, in decreasing size as the sulfate concentration is raised. The flat hexamer is the single exception; it appears to require more acidic solutions. The degree of hydroxo- versus oxo-bridges with changing solution conditions is assessed within the broader context of the condensates. Of specific interest is the identification of these products as they relate to the use of hydrolysis reactions in designing new materials.


Multivariate Assessment and Risk Ranking of Pesticide Residues in Citrus Fruits.
Pesticides are extensively used in the cultivation and postharvest protection of citrus fruits, therefore continuous monitoring and health risk assessments of their residues are required. This study aimed to investigate the occurrence of pesticide residues on citrus fruits and to evaluate the acute and chronic risk for adults and children. The risk ranking of twenty-three detected pesticides was carried out according to a matrix ranking scheme. Multiple residues were detected in 83% of 76 analyzed samples. In addition, 28% contained pesticides at or above maximum residue levels (MRLs). The most frequently detected pesticides were imazalil, azoxystrobin, and dimethomorph. According to the risk ranking method, imazalil was classified in the high-risk group, followed by prochloraz, chlorpyrifos, azinphos-methyl, tebufenpyrad, and fenpiroximate, which were considered to pose a medium risk. The majority of detected pesticides (74%) posed a low risk. The health risk assessment indicated that imazalil and thiabendazole contribute to acute (HQa) and chronic (HQc) dietary risk, respectively. The HQc was negligible for the general population, while the HQa of imazalil and thiabendazole exceeded the acceptable level in the worst-case scenario. Cumulative chronic/acute risk (HIc/HIa) assessment showed that chronic risk was acceptable in all samples for children and adults, while the acute risk was unacceptable in 5.3% of citrus fruits for adults and 26% of citrus fruits for children. Sensitivity analyses indicated that the ingestion rate and individual body weight were the most influential risk factors.


Vibration Measurement Method of a String in Transversal Motion by Using a PSD.
A position sensitive detector (PSD) is frequently used for the measurement of a one-dimensional position along a line or a two-dimensional position on a plane, but is more often used for measuring static or quasi-static positions. Along with its quick response when measuring short time-spans in the micro-second realm, a PSD is also capable of detecting the dynamic positions of moving objects. In this paper, theoretical modeling and experiments are conducted to explore the frequency characteristics of a vibrating string while moving transversely across a one-dimensional PSD. The theoretical predictions are supported by the experiments. When the string vibrates at its natural frequency while moving transversely, the PSD will detect two frequencies near this natural frequency; one frequency is higher than the natural frequency and the other is lower. Deviations in these two frequencies, which differ from the string's natural frequency, increase while the speed of motion increases.


Slow time evolution of two-time-scale reaction-diffusion systems: the physical origin of nondiffusive transport.
We study, from a mesoscopic point of view, the slow time-scale dynamics of a mixture of chemicals in which there is a chemical reaction that occurs much faster than all other processes, including diffusion. For a simple paradigmatic model reaction, it is possible to find a reduced set of dynamical equations analytically. This procedure, which yields the same mean field equations as the macroscopic approach described by Strier and Dawson [J. Chem. Phys, 112, 825 (2000)], clarifies the physical origin of some of the terms that appear in the reduced reaction-diffusion equations, such as "negative density dependent cross diffusion terms," whose actual meaning is hard to assess within the macroscopic framework. We also present a two-time-scale reactive lattice gas automaton with which it is possible to check the validity of the analytical results and the conditions under which the reduced description holds. Using this lattice gas we also show how the differential interaction with immobile species can give rise to the formation of stable Turing patterns in a system where all the other chemicals diffuse approximately at the same rate.


Ultrastructural morphology of sarcosporidiosis in alpine ibex (Capra ibex).
The authors describe the ultrastructural morphology of the cyst wall of sarcocysts in the muscles from Ibex, found dead and sent to this department to be examined. Several samples of the diaphragm were taken from 52 Ibex of different age and sex, one Hispanic and the others from the Gran Paradiso National Park (GPNP). The samples were prepared for electron microscopy after testing for sarcocystiosis through extemporaneous microscopic examination. Eighty-six percent were positive. The morphology of the cyst wall led to the identification of three types of sarcocysts in the Ibex of the GPNP and a further type in the Hispanic one. The morphology of the sarcocysts wall is similar to the wall of the species described in the domestic ruminants from several authors.


Rhodococcus oryzae sp. nov., a novel actinobacterium isolated from rhizosphere soil of rice (Oryza sativa L.).
A Gram-stain-positive, non-motile, creamy-white actinobacterium, which has an elementary branching rod-coccus life cycle was isolated from the rhizosphere soil of rice (Oryza sativa L.) collected from Northeast Agricultural University in Harbin, Heilongjiang province, north-east PR China, and its taxonomic status was examined by using a polyphasic approach. Results from the 16S rRNA gene sequence study showed that the isolate, designated strain NEAU-CX67T, belonged to the genus Rhodococcus and formed a cluster with Rhodococcus maanshanensis DSM 44675T, Rhodococcus kronopolitis NEAU-ML12T and Rhodococcus tukisamuensis JCM 11308T (98.3, 98.1 and 97.7% gene sequence similarity, respectively). The major fatty acids were C16 : 0, 10-methyl C18 : 0, C18 : 1 ω9c and C16 : 1 ω7c. The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannoside. The major isoprenoid quinone was MK-8(H2). Whole-cell hydrolysates contained meso-diaminopimelic acid. Arabinose, galactose and ribose were detected as diagnostic sugars from whole-cell hydrolysates. Mycolic acids were detected. The genomic DNA G+C content of strain NEAU-CX67T was 64.6 mol%. Strain NEAU-CX67T exhibited low average nucleotide identity and digital DNA-DNA hybridization values with R. maanshanensis DSM 44675T (92.1 and 45.4 %) and R. tukisamuensis JCM 11308T (81.9 and 24.4 %). On the basis of results of phylogenetic, genotypic, physiological and chemotaxonomic analysis, strain NEAU-CX67T is considered to represent a novel species of the genus Rhodococcus for which the name Rhodococcus oryzae sp. nov. is proposed. The type strain is NEAU-CX67T (=DSM 107701T=CCTCC AB 2018233T).


Underestimated collateral effects of antibiotic therapy in prosthesis-associated bacterial infections.
Antibiotic treatment of infections associated with the use of indwelling medical devices in ageing and/or severely ill patients represents a significant healthcare problem due to the difficulty of treating such infections and to the various collateral effects that may be observed following the often aggressive therapy. We summarize some effects of antibiotics on the expression of virulence factors of the microorganisms which cause such infections. These effects, particularly those resulting in a stimulation of bacterial virulence, might be usefully included among the other well-known collateral effects of antibiotic therapy.


Bone development in children living on house-boats on a river in Vietnam.
With the rapid urbanization of Vietnam, living on boats has come to be associated with underprivileged socioeconomic status, and there are major concerns regarding the health of children living under such conditions. Bone development is a critical concern in children because the foundation for skeletal health is established early in life. We evaluated the bone properties of children living under underprivileged conditions on boats in Hue City, Vietnam, with respect to a number of household factors. One hundred and twenty children aged 7-11 years selected randomly from households living on boats in Hue were included in this study. Tibial and radial speed of sound (SOS) were measured by non-invasive quantitative ultrasonometry. Socioeconomic profiles, health promotion proficiency, and nutritional intake of households were assessed by structured interview. The bone properties of 60 children aged 7-11 living on land were also assessed as controls. The Z-scores of tibial and radial SOS of boat children were -0.16 +/- 0.89 and -0.24 +/- 0.75 (mean +/- SD), respectively. Tibial SOS exhibited a significant correlation with radial SOS (r = 0.39, P < 0.01). Among the household factors examined, the educational level of fathers (P < 0.05) and the health promotion proficiency (P < 0.05) of households exhibited positive associations with the tibial bone properties of the children. The tibial and radial SOS of boat children were lower than those of children living on land (P = 0.001 and P = 0.086, respectively). The results of the present study revealed the underdevelopment of bone properties in children living on houseboats, which was correlated with their living conditions.


The Role of Preterm Birth in the Association Between Opioid Maintenance Therapy and Neonatal Abstinence Syndrome.
Pregnant women treated with methadone as opioid maintenance therapy are more likely than women treated with buprenorphine to deliver preterm. Preterm birth is associated with less risk of neonatal abstinence syndrome (NAS). We sought to assess the role of preterm birth as a mediator of the relationship between in utero exposure to methadone and NAS compared with buprenorphine. We studied 716 women receiving methadone or buprenorphine and delivering liveborn infants at Magee-Womens Hospital, Pittsburgh, Pennsylvania (2013-15). We implemented inverse probability weighted marginal structural models to isolate the role of preterm birth (<37 weeks' gestation). Weights accounted for confounding by maternal age, race, insurance, parity, delivery year, marital, employment, hepatitis C, and smoking status. Approximately 57% of the cohort were treated with methadone. Preterm birth was more common in methadone-exposed pregnancies (25% versus 14%). The incidence of NAS treatment was higher in methadone compared with buprenorphine-exposed infants (65% vs 49%), and term compared with preterm births (64% vs 36%). For every 100 infants liveborn to mothers treated for opioid dependence, there were 13 excess cases of NAS among infants exposed to methadone compared with buprenorphine (adjusted risk difference [RD] 13.3, 95% confidence interval [CI] 5.7, 20.9). Among term births, this increased to 17 excess cases of NAS in methadone- compared with buprenorphine-exposed (RD 16.7, 95% CI 9.3, 24.0). The further increased risk of NAS associated with methadone use vs buprenorphine in term deliveries emphasises the utility of buprenorphine in clinical settings aimed at decreasing NAS.


Human renal gamma-glutamyltransferase hydrolysis and transfer reactions with glutathione as substrate.
The hydrolysis and transfer reactions of purified human renal gamma-glutamyltransferase were studied in vitro with glutathione as substrate at pH and substrate concentration reflecting the physiological conditions. The pH optimum ranged from 7.48 to 8.44 for hydrolysis and 7.90 to 8.92 for transfer with glutamine as acceptor. The Michaelis constants for glutathione were 13 microM in hydrolysis and 58 microM in transfer reactions respectively. Inhibition of transfer occurred for glutathione concentrations above 0.4 mM. Various ions, urea, creatinine, uric acid and L-amino acids were shown to have no appreciable effect on both reactions except L-glutamine which acts as an activator on the hydrolysis activity. Taken together, our results, if they are transposable in vivo would be relevant of an enzyme acting like an hydrolase rather than like a transferase.


Dual Recombinase-Based Mouse Models Help Decipher Cancer Biology and Targets for Therapy.
The advent of next-generation sequencing (NGS) and single-cell profiling technologies has revealed the complex and heterogenous ecosystem of human tumors under steady-state and therapeutic perturbation. Breakthroughs in the development of genetically engineered mouse models (GEMM) of human cancers that are based on the combination of two site-specific recombinase systems [dual-recombinase system (DRS)] offer fundamental new possibilities to elucidate and understand critical drivers of the diverse tumor phenotypes and validate potential targets for therapy. Here, we discuss opportunities DRS-based cancer GEMMs offer to model, trace, manipulate, and functionally investigate established cancers, their interactions with the host, and their response to therapy.


The role of prostatitis in prostate cancer: meta-analysis.
Use systematic review methods to quantify the association between prostatitis and prostate cancer, under both fixed and random effects model. Case control studies of prostate cancer with information on prostatitis history. All studies published between 1990-2012, were collected to calculate a pooled odds ratio. the selection criteria are as follows: human case control studies; published from May 1990 to July 2012; containing number of prostatitis, and prostate cancer cases. In total, 20 case control studies were included. A significant association between prostatitis and prostate cancer was found, under both fixed effect model (pooled OR=1.50, 95%CI: 1.39-1.62), and random effects model (OR=1.64, 95%CI: 1.36-1.98). Personal interview based case control studies showed a high level of association (fixed effect model: pooled OR=1.59, 95%CI: 1.47-1.73, random effects model: pooled OR= 1.87, 95%CI: 1.52-2.29), compared with clinical based studies (fixed effect model: pooled OR=1.05, 95%CI: 0.86-1.28, random effects model: pooled OR= 0.98, 95%CI: 0.67-1.45). Additionally, pooled ORs, were calculated for each decade. In a fixed effect model: 1990's: OR=1.58, 95% CI: 1.35-1.84; 2000's: OR=1.59, 95% CI: 1.40-1.79; 2010's: OR=1.37, 95% CI: 1.22-1.56. In a random effects model: 1990's: OR=1.98, 95% CI: 1.08-3.62; 2000's: OR=1.64, 95% CI: 1.23-2.19; 2010's: OR=1.34, 95% CI: 1.03-1.73. Finally a meta-analysis stratified by each country was conducted. In fixed effect models, U.S: pooled OR =1.45, 95%CI: 1.34-1.57; China: pooled OR =4.67, 95%CI: 3.08-7.07; Cuba: pooled OR =1.43, 95%CI: 1.00-2.04; Italy: pooled OR =0.61, 95%CI: 0.13-2.90. In random effects model, U.S: pooled OR=1.50, 95%CI: 1.25-1.80; China: pooled OR =4.67, 95%CI: 3.08-7.07; Cuba: pooled OR =1.43, 95%CI: 1.00-2.04; Italy: pooled OR =0.61, 95%CI: 0.13-2.90. the present meta-analysis provides the statistical evidence that the association between prostatitis and prostate cancer is significant.