Human papillomavirus infections in children: the potential role of maternal transmission.
To date, more than 100 types of human papillomavirus (HPV) have been identified. In the past 20 years, there has been an increasing interest in HPVs because of their potential role in the pathogenesis of malignant tumors. HPV infections are known to affect predominantly adult, sexually active age groups, whereas skin warts, at various anatomic sites, are usually associated with younger individuals. The modes of viral transmission in children remain controversial, including perinatal transmission, auto- and hetero-inoculation, sexual abuse, and, possibly, indirect transmission via fomites. Recent studies on perinatal infection with HPV have been inconclusive. It is still unclear how frequently perinatal infection progresses to clinical lesions, whether genital, laryngeal, or oral. Conflicting reports have been published on the prevalence of HPV infections in children. The current consensus is, however, that newborn babies can be exposed to cervical HPV infection of the mother. The detection rate of HPV DNA in oral swabs of newborn babies varies from 4% to 87%. The concordance of HPV types detected in newborn babies and their mothers is in the range of 57% to 69%, indicating that the infants might acquire the HPV infection post-natally from a variety of sources. HPV antibodies have been detected in 10% to 57% of the children, and there is usually no correlation between seropositivity and the detection of HPV DNA in either the oral or the genital mucosa. There is also evidence that transmission in utero or post-natal acquisition is possible. The mode of in utero transmission remains unknown, but theoretically the virus could be acquired hematogenously, by semen at fertilization, or as an ascending infection in the mother. The understanding of viral transmission routes is important, particularly because several vaccination programs are being planned worldwide. The serologic response to HPV detected in different populations of young women or women at risk of cervical cancer might be due to genital infections, but the possibility that HPV infection has been acquired earlier in life through the oral mucosa or respiratory tract cannot be ruled out.


Evidence that the maternal pituitary suppresses the secretion of relaxin in the pregnant rat.
The role of the pituitary in regulating relaxin synthesis and secretion by the corpus luteum during the second half of pregnancy was investigated by hypophysectomizing rats carrying either one conceptus (1C) or a full complement (FC) of conceptuses (n greater than or equal to 8) on day 13 of pregnancy. Serum and luteal relaxin levels, serum progesterone levels, and luteal weights in 1C rats were markedly lower during the period from days 14 through 20 of pregnancy than those in FC rats, as has been previously reported. After hypophysectomy of 1C rats (H1C), serum relaxin levels, serum progesterone levels, and corpus luteum weights increased to values that were not significantly different from those of FC rats. Additionally, hypophysectomized FC rats (HFC) had higher serum relaxin levels than FC rats. Luteal relaxin content was unaffected by hypophysectomy in spite of increased relaxin secretion. Other workers have suggested that placental testosterone may support luteal function during the second half of pregnancy. Serum testosterone levels in 1C rats were markedly lower than those in FC rats, but did not increase after hypophysectomy in either H1C or HFC rats. It is concluded that the putuitary has a suppressive effect on relaxin secretion (and perhaps synthesis) as well as progesterone secretion and corpus luteum growth, and that increased luteal function after hypophysectomy is not due to increased placental testosterone secretion.


[Calcium-blocking effect of nitro compounds in human platelets: correlation with changes in the cyclic guanosine monophosphate level].
The effects of nitrates on Ca2+ increase and cyclic nucleotide content in human platelets were studied. Nitroglycerin, isosorbide dinitrate and sodium nitroprusside were found to inhibit the intracellular Ca2+ increase induced by the platelet activating factor, ADP and a stable thromboxane A2 analog--U46619. The inhibiting effect of sodium nitroprusside manifested itself at lower concentrations than those of nitroglycerin and isosorbide dinitrate. Nitroglycerin suppressed the Mn2+ entry into the cells and caused a 2-fold increase of the cGMP content which correlates with the calcium blocking activity. Methylene blue, a guanylate cyclase and glutathione reductase inhibitor, decreased the calcium blocking effect of nitroglycerin and its influence on the cyclic nucleotide content but failed to suppress the inhibitory effect of sodium nitroprusside. The data obtained suggest that the effects of nitrates on platelets are mediated by their influence on guanylate cyclase which leads to a cyclic nucleotide content increase and to a calcium blocking effect.


Modulation of stacking interactions by transition-metal coordination: ab initio benchmark studies.
A series of ab initio calculations are used to determine the C--Hpi and pipi-stacking interactions of aromatic rings coordinated to transition-metal centres. Two model complexes have been employed, namely, ferrocene and chromium benzene tricarbonyl. Benchmark data obtained from extrapolation of MP2 energies to the basis set limit, coupled with CCSD(T) correction, indicate that coordinated aromatic rings are slightly weaker hydrogen-bond acceptors but are significantly stronger hydrogen-bond donors than uncomplexed rings. It is found that pipi stacking to a second benzene is stronger than in the free benzene dimer, especially in the chromium case. This is assigned, by use of energy partitioning in the local correlation method, to dispersion interactions between metal d and benzene pi orbitals. The benchmark data is also used to test the performance of more efficient theoretical methods, indicating that spin-component scaling of MP2 energies performs well in all cases, whereas various density functionals describe some complexes well, but others with errors of more than 1 kcal mol(-1).


Highly Controllable Etchless Perovskite Microlasers Based on Bound States in the Continuum.
Lead halide perovskites have been promising materials for lasing applications. Despite that a series of perovskite microlasers have been reported, their lasing modes are confined by either the as-grown morphology or the etched boundary. The first one is quite random and incompatible with integration, whereas the latter one strongly spoils the laser performances. Herein, we propose and experimentally demonstrate a robust and generic mechanism to realize well-controlled perovskite microlasers without the etching process. By patterning a one-dimensional polymer grating onto a perovskite film, we show that the symmetry-protected bound states in the continuum (BICs) can be formed in it. The intriguing properties of BICs including a widely spread mode profile and high Q factor, associated with the exceptional gain of perovskite, produce single-mode microlasers with high repeatability, controllability, directionality, and a polarization vortex. This mechanism can also be extended to two-dimensional nanostructures, enabling BIC lasers with different topological charges.


Fibroblast growth factor-4 enhanced G2 arrest and cell survival following ionizing radiation.
Fibroblast growth factors (FGFs) bind to cell membrane receptors and activate signal transduction pathways related to cell growth, angiogenesis, and tumorigenesis. FGFs have been shown to be abundantly expressed in some of the human tumors, which are known to be poorly responsive to radiation therapy. Using adrenal cortical carcinoma cells genetically engineered to express FGF-4, we have tested cellular survival following exposure to ionizing radiation. We report here that FGF-4 enhances cellular capacity to survive ionizing radiation. Furthermore, cell cycle analysis shows a pronounced increase in the duration of G2 arrest, suggesting perturbation of a cell cycle checkpoint. These findings implicate fibroblast growth factor-mediated signal transduction in cellular resistance of human tumors to radiation therapy.


Clinical studies investigating the use of leuprorelin in Asian women with endometriosis: a review.
We aimed to examine how leuprorelin has been studied for the treatment of women with endometriosis in Asia. We conducted a literature search of PubMed, the Cochrane Library and ClinicalTrials.gov. This review includes randomised trials of women with endometriosis treated with leuprorelin in Asia. Phase I-IV clinical trials published between January 1 2000 and December 31 2016 and written in English were included. Four studies were identified, showing that leuprorelin significantly improves pain and quality of life. The oestrone and oestradiol levels are decreased by leuprorelin but can be increased using an 'add-back' therapy with conjugated equine oestrogen and methoxyprogesterone. Menopause is more common in women treated with leuprorelin. The bone mineral density is reduced in women treated with leuprorelin. There are limited studies investigating the use of leuprorelin for the treatment of endometriosis in Asian populations. However, the research that has been conducted supports the use of leuprorelin in an Asian population.


Dens Axis Vertebroplasty Combined with C 3 Vertebral Body Arthroplasty. Case Study.
Spinal tumors are most commonly located in the thoracic and lumbar spine, less commonly in the cervical section of the spine. Diagnosis is usually late and surgery is not radical. Myeloma is one of the most frequent metastatic spinal tumors. Surgical treatment of osteolytic lesions in the spine involves posterior and anterior stabilization, full or partial tumorectomies as well as decompression of neural structures. Bone cement injection has been increasingly used in plastic surgery of vertebral bodies and is most frequently performed percutaneously in the thoracic and lumbar spine. Cervical vertebroplasty can be performed both percutaneously and after anterior exposure of the spine. The dens axis can also be approached transorally. The safest surgical technique seems to be the Southwick approach, which allows exposure of the spine at C2-Th2 and, if necessary, can be extended both proximally and distally. Cemented cervical vertebroplasty, especially dens axis vertebroplasty, shows good results, yet this technique has rarely been described in the literature. It has the advantage of early patient mobility and little limitation of motion of the spine. Cervical vertebroplasty can be successfully combined with other procedures utilizing the same surgical approach in a single-stage operation. Post-resection anterior stabilization of the cervical spine with plates and vertebral body prosthesis allows for good stability of the spine and makes it possible to restore the spinal axis and curvatures.


Associative and spontaneous appraisal processes independently contribute to anger elicitation in daily life.
There has been a great deal of debate concerning the antecedents of anger, with appraisal theorists emphasizing the role of hostile interpretations and cognitive neo-associationistic theorists emphasizing the role of more basic associative processes. Recently, theorists have sought to reconcile these views by acknowledging the role of both associative and inferential processes, and the current investigation drew upon recent social-cognitive research to test this compromise. Individual differences in hostile inferences and associations were assessed in an implicit cognitive paradigm, and relevant outcomes were assessed in a daily diary protocol. Implicit hostile inferences predicted both anger and aggression in daily life, and such relationships were mediated by propensities toward hostile interpretations in daily life. Hostile associations also predicted anger in daily life, but this relationship proved to be independent of daily hostile interpretations. Results therefore support a model that acknowledges the role of both associative and appraisal processes in anger elicitation.


A DNA hypermethylation profile reveals new potential biomarkers for the evaluation of prognosis in urothelial bladder cancer.
DNA hypermethylation has emerged as a molecular biomarker for the evaluation of cancer diagnosis and prognosis. We define a methylation signature of bladder cancer and evaluate whether this profile assesses prognosis of patients. Genome-wide methylation analysis was performed on 70 tumor and 10 normal bladder samples. Hypermethylation status of 1505 CpGs present in the promoter region of 807 genes was studied. Thirty-three genes were significantly hypermethylated in ≥10% of the tumors. Three clusters of patients were characterized by their DNA methylation profile, one at higher risk of dead of disease (p = 0.0012). Association between cluster distribution and stage (p = 0.02) or grade (p = 0.02) was demonstrated. Hypermethylation of JAK3 and absence of hypermethylation of EYA4, GAT6, and SOX1 were associated with low-grade non-invasive disease. On the other hand, in high-grade invasive disease hypermethylation of CSPG2, HOXA11, HOXA9, HS3ST2, SOX1, and TWIST1 was associated with muscle invasiveness. A panel of hypermethylated genes including APC, CSPG2, EPHA5, EYA4, HOXA9, IPF1, ISL1, JAK3, PITX2, SOX1, and TWIST1 predicted cancer-specific survival and SOX1 (HR = 3.46), PITX2 (HR = 4.17), CSPG2 (HR = 5.35), and JAK3 hypermethylation (HR = 0.19) did so independently. Silencing of genes by hypermethylation is a common event in bladder cancer and could be used to develop diagnostic and prognostic markers. Combined hypermethylation of SOX1, PITX2, or CSPG2 signals patients at higher risk of death from bladder cancer.


Investigation of Bladder Cancer Cell Response to Cryoablation and Adjunctive Cisplatin Based Cryo/Chemotherapy.
Due to a rising annual incidence of bladder cancer, there is a growing need for development of new strategies for treatment. In 2018, the World Cancer Research Fund and other groups reported that there were ~550,000 new cases worldwide of bladder cancer. It has been further estimated that >200,000 individuals die annually from bladder cancer worldwide. Various treatment options exist. However, many if not all remain suboptimal. While the preferred chemotherapeutic options have changed in the past few years there have been few advances in the bladder cancer medical device field. Cryoablation is now being evaluated as a new option for the treatment of bladder cancer. While several studies have shown cryoablation to be promising for the treatment of bladder cancer, a lack of basic information pertaining to dosing (minimal lethal temperature) necessary to destroy bladder cancer has limited its use as a primary therapeutic option. Concerns with bladder wall perforation and other side effects have also slowed adoption. In an effort to detail the effects of freezing on bladder cancer, two human bladder cancer cell lines, SCaBER and UMUC3, were evaluated in vitro. SCaBER, a basal subtype of muscle invasive bladder cancer, and UMUC3, an intermediate transitional cell carcinoma, are both difficult to treat but are reportedly responsive to most conventional treatments. SCaBER and UMUC3 cells were exposed to a range of freezing temperatures from -10 to -25°C and compared to non-frozen controls. The data show that a single 5 minute freeze to -10°C did not affect cell viability, whereas -15°C and -20°C results in a significant reduction in viability 1 day post freeze to <20%. These populations, however, were able to recover in culture. A complete loss of cell viability was found following a single freeze at -25°C. Application of a repeat (double) freeze resulted in complete cell death at -20°C. In addition to freezing alone, studies investigating the impact of adjunctive low dose (1 μM) cisplatin pre-treatment (30 minutes and 24 hours) in combination with freezing were conducted. The combination of 30 minute cisplatin pre-treatment and mild (-15°C) freezing resulted in complete cell death. This suggests that subclinical doses of cisplatin may be synergistically effective when combined with freezing. In summary, these in vitro results suggest that freezing to temperatures in the range of -20 to 25°C results in a high degree of bladder cancer cell destruction. Further, the data describe a potential combinatorial chemo/cryo therapeutic strategy for the treatment of bladder cancer.


Primary progressive aphasia in a bilingual woman.
Multilingual aphasias are common because most people in the world know more than one language, but little is known of these syndromes except in patients who have had a stroke. We present a 76-year-old right-handed woman, fluent in English and Chinese, who developed anomia at age 70 and then progressed to aphasia. Functional neuroimaging disclosed mild left temporoparietal hypometabolism. Neurolinguistic testing was performed in both English and Chinese, representing a unique contribution to the literature. Results revealed conduction-like aphasia that was comparable in the two languages, although English was slightly better preserved. Primary progressive aphasia has disrupted 2 languages in a similar manner, suggesting their close neuroanatomic relationship in this case.


A multivariate two-sample mean test for small sample size and missing data.
We develop a new statistic for testing the equality of two multivariate mean vectors. A scaled chi-squared distribution is proposed as an approximating null distribution. Because the test statistic is based on componentwise statistics, it has the advantage over Hotelling's T2 test of being applicable to the case where the dimension of an observation exceeds the number of observations. An appealing feature of the new test is its ability to handle missing data by relying on only componentwise sample moments. Monte Carlo studies indicate good power compared to Hotelling's T2 and a recently proposed test by Srivastava (2004, Technical Report, University of Toronto). The test is applied to drug discovery data.


Anxiety and personality traits in patients with muscle related temporomandibular disorders.
This study tested the hypothesis that muscle related temporomandibular disorder patients with cervical muscle pain exhibit greater degree of psychological distress compared with patients without cervical muscle pain and controls. Thirty-eight muscle related temporomandibular disorder patients including 10 patients with cervical muscle pain and 41 healthy individuals as controls participated in the study. State and trait anxiety levels were assessed with the Spielberger's state and trait anxiety inventory. Personality traits (extroversion, neuroticism, psychoticism and social desirability) were assessed using the Eysenck's personality questionnaire, and the pain intensities described over the muscles were recorded using a 100 mm visual analogue scale. The muscle related temporomandibular disorder patients, in general, exhibited significantly higher degrees of neuroticism and trait anxiety. The patients with cervical muscle pain demonstrated a significantly higher level of psychoticism compared with the patients without cervical muscle pain and the controls and a significantly higher state anxiety level than the controls. They also demonstrated higher pain intensities in masseter and temporalis muscles compared with patients without cervical muscle pain. It has been suggested that either subjects with psychological distress are prone to temporomandibular disorders, or psychological distress is a manifestation of existing chronic pain conditions. The present findings demand further investigations and broader approach in management, as muscle related temporomandibular disorder patients with cervical muscle pain were both physically and psychologically compromised to a greater degree compared with patients without cervical muscle pain.


Neuroglobin upregulation offers neuroprotection in traumatic brain injury.
The aim of this study was to investigate rat neuroglobin (rNGB) expression level after traumatic brain injury (TBI) and further study its neuroprotective effects in TBI when it was overexpressed in adenoviral vector. The Wistar rats (280-320 g) were divided into control, 12 and 36 hours after TBI groups (n = 3) and their TBI model was established. Subsequently, NGB expression level was examined by Western blot and immunohistochemical. Beyond that, adenoviral vectors pAdEasy-rNGB-GFP and pAdEasy-GFP were constructed and transfected into the rat brain respectively (pAdEasy-GFP was control), and the neuroprotective effects were examined by immunohistochemical. Immunohistochemical and Western blot results demonstrated that NGB expression level was increased at 12 and 36 hours after TBI injury compare with control. Meanwhile, the pAdEasy-rNGB-GFP transfected rats suffered less necrosis and apoptosis compare to control. NGB was upregulated in TBI and overexpressed rNGB had a significant neuroprotection in TBI. However, the mechanism remained unknown. This study suggested that rNGB overexpression may be a new strategy for treating of TBI.


Physical, sexual and psychological intimate partner violence and non-partner sexual violence against women and girls: a systematic review protocol for producing global, regional and country estimates.
In 2013, the WHO published the first global and regional estimates on physical and sexual intimate partner violence (IPV) and non-partner sexual violence (NPSV) based on a systematic review of population-based prevalence studies. In this protocol, we describe a new systematic review for the production of updated estimates for IPV and NPSV for global monitoring of violence against women, including providing the baseline for measuring Sustainable Development Goal to eliminate all forms of violence against women and girls. The systematic review will update and extend the previous search for population-based surveys (either nationally or subnationally representative) conducted among women aged 15+ years that measured the prevalence of physical, sexual, psychological and physical and/or sexual IPV, NPSV or sexual violence by any perpetrator up to December 2019. Data will be extracted separately for all age groups, setting (urban/rural), partnership status (currently partnered/ever partnered/all women) and recall period (lifetime prevalence/past 12 months). Studies will be identified from electronic searches of online databases of EMBASE, MEDLINE, Global Health and PsycInfo. A search of national statistics office homepages will be conducted for each country to identify reports on population-based, national or subnational studies that include data on IPV or NPSV published outside academic journals. Two reviewers will be involved in quality assessment and data extraction of the review. The review is planned to be updated on a continuous basis. All findings will undergo a country consultation process. Formal ethical approval is not required, as primary data will not be collected. This systematic review will provide a basis and a follow-up tool for global monitoring of the Sustainable Development Goal Target 5.2 on the elimination of all forms of violence against women and girls. CRD42017054100.


Genetic toxicity assessment: employing the best science for human safety evaluation. Part I: Early screening for potential human mutagens.
Results of genetic toxicology tests are used by FDA's Center for Drug Evaluation and Research as a surrogate for carcinogenicity data during the drug development process. Mammalian in vitro assays have a high frequency of positive results which can impede or derail the drug development process. To reduce the risk of such delays, most pharmaceutical companies conduct early non-GLP (good laboratory practices) studies to eliminate drug candidate with mutagenic or clastogenic activity. Early screens include in silico structure activity assessments and various iterations of the ultimate regulatory mandated GLP studies.


A Cell-Surface Membrane Protein Signature for Glioblastoma.
We present a systems strategy that facilitated the development of a molecular signature for glioblastoma (GBM), composed of 33 cell-surface transmembrane proteins. This molecular signature, GBMSig, was developed through the integration of cell-surface proteomics and transcriptomics from patient tumors in the REMBRANDT (n = 228) and TCGA datasets (n = 547) and can separate GBM patients from control individuals with a Matthew's correlation coefficient value of 0.87 in a lock-down test. Functionally, 17/33 GBMSig proteins are associated with transforming growth factor β signaling pathways, including CD47, SLC16A1, HMOX1, and MRC2. Knockdown of these genes impaired GBM invasion, reflecting their role in disease-perturbed changes in GBM. ELISA assays for a subset of GBMSig (CD44, VCAM1, HMOX1, and BIGH3) on 84 plasma specimens from multiple clinical sites revealed a high degree of separation of GBM patients from healthy control individuals (area under the curve is 0.98 in receiver operating characteristic). In addition, a classifier based on these four proteins differentiated the blood of pre- and post-tumor resections, demonstrating potential clinical value as biomarkers.


Making the Most From the Money.
How to reduce unwarranted variation in the NHS was the focus of debate among experts brought together for HSJ's latest roundtable, as Alison Moore reports.


Promoter activity and gene structure of rabbit FKBP52.
A 0.9-kb fragment situated directly upstream of the first ATG of rabbit FKBP52 is rich in acceptor sites for transcription factors, contains a CAAT box at -197 and could represent the proximal promoter of this immunophilin. Transvection analysis of this fragment showed strong promoter activity on the expression of a reporter gene. Deletions at the 5' end of this fragment showed that a basic sequence of 155 base pairs upstream of the CAAT box was sufficient to enhance luciferase expression an average 220-fold compared to the empty vector. This sequence, which contains acceptor sites for transcription factors of the EGR family and heat-shock factors, is closely homologous to 110 base pairs situated directly 5' of FKBP52 exon 1 in human chromosome 12p13.3, suggesting that these transcription factors could be involved in the regulation of the gene in both species. Furthermore, the upstream region of RbFKBP52 contains a large proportion of SINEs (C-repeats, Alu analogs), some of which include the A and B boxes required for transcription of RNA polymerase III, and poly A tracts. RbFKBP52, like HuFKBP52, is made up of 10 exons and 9 introns, a feature shared with other large immunophilins such as FKBP65 and Cyclophilin 40, and which appears widely conserved.


The transcallosal interforniceal approach to the third ventricle: anatomic and microsurgical aspects.
The ability to visualize median-sagittal brain structures by magnetic resonance imaging improves planning for surgery to treat lesions of the third ventricle. The most appropriate path to the third ventricle is the transcallosal approach. The present study was undertaken to describe the surgical anatomy and landmarks encountered during this approach. The transcallosal-interforniceal approach was undertaken in 30 formalin-fixed brains using an operating microscope. The surface landmarks for the approach pathway were the two points, P5 and P7, located 5 and 7 cm anterior to the central sulcus, respectively. Using these two points on the cortical surface as references, a variety of measurements were made to provide quantitative information about distances between brain structures that are encountered during the surgical approach. Measurements that were made include the following: 1) the distance between P5 and the cingulate sulcus, 2) the distance between the cingulate sulcus and the corpus callosum, 3) the height of the corpus callosum, 4) the distance between the anterior commissure and the foramen of Monro, and 5) the distance between the lower margin of the corpus callosum and the fornix. Mean values for these key measurements were as follows: 1) 23.96 mm (range, 15.0-32.0 mm); 2) 13.50 mm (range, 8.0-20.0 mm) with reference to P5 and 12.73 mm (range, 16.0-18.0 mm) with reference to P7; 3) 6.12 mm (range, 4.0-8.0 mm) with reference to P5 and 6.60 mm (range, 4.0-9.0 mm) with reference to P7; 4) 4.96 mm (range, 2.5-10.0 mm), independent of P5 and P7; and 5) 8.46 mm (range, 3.0-16.0 mm) with reference to P5 and 11.04 mm (range, 6.0-22.0 mm) with reference to P7. The detailed quantitative information obtained in this study about the interforniceal approach permitted definition of surgical approach pathways that preserve important anatomic structures, such as the motor strip, genu of the corpus callosum, fornical commissure (hippocampal commissure), anterior commissure, and fornical columns. The approach through this surgical corridor can easily be planned and performed in individual cases using median-sagittal magnetic resonance imaging scans.


Polytrauma and life care planning: managing the complex interaction of multiple injuries.
Military personnel, who have sustained multiple injuries, or polytrauma, are returning home with a novel set of challenging injuries and disabilities. These emerging injury patterns require specialized rehabilitation and continual coordination of care. One technique to assess the current and future disability-related needs of an individual who sustains polytrauma is life care planning. The life care plan (LCP) is a dynamic document based upon published standards of practice, comprehensive assessments, data analysis, and research. The purpose of this article is to introduce the life care plan as an established and successful approach for meeting the complex and comprehensive needs of individuals with polytrauma. Additionally this article includes multiple case examples to help illustrate the applicability of life care planning.


Postnatal changes in insulin binding in slow and fast-twitch rabbit skeletal muscles.
Changes of insulin binding characteristics (number of receptors, Kd) were studied in the semimembranosus proprius (SMP) and psoas major (PM) muscle from birth to adult stage. The Kd was about 0.15 10(-9) M in both muscles and did not change with age. The numbers of receptors were similar in both muscles at birth and changed differently thereafter to reach 1.3 fmoles per mg of muscle in the PM and 5.6 in the SMP muscle.


Utility of Integrated Analysis of Pharmacogenomics and Pharmacometabolomics in Early Phase Clinical Trial: A Case Study of a New Molecular Entity.
In this report, we present a case study of how pharmacogenomics and pharmacometabolomics can be useful to characterize safety and pharmacokinetic profiles in early phase new drug development clinical trials. During conducting a first-in-human trial for a new molecular entity, we were able to determine the mechanism of dichotomized variability in plasma drug concentrations, which appeared closely related to adverse drug reactions (ADRs) through integrated omics analysis. The pharmacogenomics screening was performed from whole blood samples using the Affymetrix DMET (Drug-Metabolizing Enzymes and Transporters) Plus microarray, and confirmation of genetic variants was performed using real-time polymerase chain reaction. Metabolomics profiling was performed from plasma samples using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. A GSTM1 null polymorphism was identified in pharmacogenomics test and the drug concentrations was higher in GSTM1 null subjects than GSTM1 functional subjects. The apparent drug clearance was 13-fold lower in GSTM1 null subjects than GSTM1 functional subjects (p < 0.001). By metabolomics analysis, we identified that the study drug was metabolized by cysteinylglycine conjugation in GSTM functional subjects but those not in GSTM1 null subjects. The incidence rate and the severity of ADRs were higher in the GSTM1 null subjects than the GSTM1 functional subjects. Through the integrated omics analysis, we could understand the mechanism of inter-individual variability in drug exposure and in adverse response. In conclusion, integrated multi-omics analysis can be useful for elucidating the various characteristics of new drug candidates in early phase clinical trials.


Effects of plant size, temperature, and light intensity on flowering of Phalaenopsis hybrids in Mediterranean greenhouses.
Mediterranean greenhouses for cultivation of Phalaenopsis orchids reproduce the warm, humid, and shaded environment of tropical underbrush. Heating represents the highest production cost, due to the high thermal requirements and the long unproductive phase of juvenility, in which plants attain the critical size for flowering. Our researches aimed to investigate the effect of plant size, temperature, and light intensity, during the phase of flower induction, on flowering of modern genotypes selected for Mediterranean greenhouses. Three experiments were carried out to compare (i) plant size: reduced size versus size considered optimal for flowering (hybrids "Sogo Yukidian," "Chain Xen Diamond," and "Pinlong"); (ii) temperature: moderate reduction of temperature versus standard thermal regime (hybrid "Premium"); (iii) light intensity: supplemental lighting versus reference light intensity (hybrid "Premium"). The premature exposure of plants to the inductive treatment delayed the beginning of flowering and reduced the flower stem quality, in all the tested hybrids. In "Premium," the lower temperature did not affect flowering earliness and commercial quality of flower stems compared to the standard regime, whereas it promoted stem branching. In the same hybrid, supplemental lighting anticipated flowering and promoted the emission of the second stem and the stem branching, compared to the reference light regime.


A component-based FPGA design framework for neuronal ion channel dynamics simulations.
Neuron-machine interfaces such as dynamic clamp and brain-implantable neuroprosthetic devices require real-time simulations of neuronal ion channel dynamics. Field-programmable gate array (FPGA) has emerged as a high-speed digital platform ideal for such application-specific computations. We propose an efficient and flexible component-based FPGA design framework for neuronal ion channel dynamics simulations, which overcomes certain limitations of the recently proposed memory-based approach. A parallel processing strategy is used to minimize computational delay, and a hardware-efficient factoring approach for calculating exponential and division functions in neuronal ion channel models is used to conserve resource consumption. Performances of the various FPGA design approaches are compared theoretically and experimentally in corresponding implementations of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) synaptic ion channel models. Our results suggest that the component-based design framework provides a more memory economic solution, as well as more efficient logic utilization for large word lengths, whereas the memory-based approach may be suitable for time-critical applications where a higher throughput rate is desired.


Characteristics of microblotting assay using immunoliposomes.
To clarify the applicability of a liposome immunoblotting assay to microassay systems, the effects of the sample volume blotted on polyvinylidiene fluoride (PVDF) membrane on the sensitivity and signal intensity were studied and compared with those in a conventional immunoblotting assay utilizing enzyme-labeled antibody. In the liposome immunoblotting assay, signal intensities per unit area (signal density) were almost the same or increased slightly with decreasing blotted sample volume (from 20 to 2 microl) at the same concentration of analyte (human IgM) adsorbed on PVDF membrane. A substrate, 4-chloro-1-naphtol, for color development formed colored precipitates inside the liposomes. Thus, the colored signal was detected without loss of intensity. On the other hand, in the conventional immunoblotting assay, signal densities decreased with decreasing sample volume at the same concentration of analyte. This is caused by partial losses of the colored signal into the substrate solution by diffusion, because the fraction of loss increases with decreasing sample volume. These results show that the liposome immunoblotting assay is a promising method for the detection of analytes blotted in small areas, because its sensitivity is higher than that of the conventional blotting assay.


A protein covalently bound to ColE1 DNA.
ColE1 DNA was isolated from Escherichia coli as a relaxation complex of supercoiled DNA and proteins. Treatment of the complex with either protein-denaturing agents (SDS, phenol etc.) or proteolytic enzymes converted the supercoiled DNA to an open-circular form (relaxation). The relaxation complex was separately labelled in vivo with [3H]Leu or [14C]Leu, [35S]Met or (32P)phosphate and extensively purified. Complete hydrolysis of the relaxed complex with DNase I and P1 nuclease produced a 36-kDa protein which, we believe, is covalently bound to ColE1 DNA. On the other hand, the relaxed complex was treated with tosylphenylalanylchloromethane-treated-trypsin and the DNA-peptide(s) produced was (were) isolated and digested with the nucleases as above. The resulting nucleotidylpeptide(s) was (were) isolated by DEAE-Sephadex chromatography. The only 5'-dCMP was released from the nucleotidylpeptide(s) by snake venom phosphodiesterase treatment. O-Phosphoserine was found in acid hydrolysates of the DNA-peptide(s). We suggest that in the relaxation event the 36-kDa protein becomes covalently linked to ColE1 DNA via a phosphodiester bond between dC and the serine residue.


Embodied Perception: A Proposal to Reconcile Affordance and Spatial Perception.
Proffitt's embodied approach to perception is deeply indebted to Gibson's ecological approach to visual perception, in particular the idea that the primary objects of perception are affordances or what the environment offers for action. Yet, rather than directly addressing affordance perception, most of the empirical work evaluating Proffitt's approach focuses on the perception of spatial properties of the environment. We propose that theoretical and empirical efforts should be directed toward an understanding of the relationship between affordance perception and spatial perception, keeping in mind that this relationship is nontrivial because affordance perception is dichotomous, whereas the perception of spatial properties is gradual. We argue that the perception of spatial properties of the environment is enslaved by affordance perception, most notably at the critical boundaries for action. To empirically scrutinize this proposition, and to solve issues raised regarding the validity of several empirical findings, we call for joint research efforts to further understanding of embodied perception.


Obesity-associated disorders in normal-weight individuals: some speculations.
A number of disorders including maturity-onset (Type II) diabetes, hypertension and hypertriglyceridemia are frequently associated with adult-onset obesity and improve with energy restriction. It is the premise of this brief review that there are patients with these disorders who are not obese according to standard criteria; but who would also respond favorably to energy restriction. It is proposed that these 'metabolically-obese, normal weight' individuals might be characterized by hyperinsulinism and possibly an increase in fat cell size, compared to patients of similar age, height and weight and/or to themselves at an earlier time. It is also proposed that in some of these individuals inactivity and diet composition might be important contributing factors, and that for them, the appropriate therapy would include exercise and altered diet composition.


[Intubation Using a Double-lumen Tube with a Combination of Fiberoptic Bronchoscope and the Glidescope in a Patient with Difficult Airway].
A 54-year-old man with lung cancer was scheduled for thoracoscopic upper lobe resection under general anesthesia. About half a year previously, he had undergone surgery for oropharyngeal cancer and tongue cancer. As a result of the surgery, elasticity of the neck skin bending of the neck were restricted (Mallampati classification IV). A narrow-bored tracheostomy tube (speech cannula) was inserted. In the operating room, the tip of a 5.0 mm ID standard tube was inserted from the tracheostomy tube, and connected to a breathing circuit. Anesthesia was induced with inhalation of sevoflurane, followed by intravenous propofol, fentanyl, and rocuronium. Four anesthesiologists were required to intubate the trachea. One person held the tracheal tube placed in the tracheotomy tube. The second person performed jaw thrusting. The third person inserted the Glidescope to shift the transplanted tongue to the side. It was then possible for the forth anesthesiologist to manage to see the glottis using a fiberoptic bronchoscope, and a double-lumen tube (DLT) could be inserted to the trachea orally. Inserting a DLT over the fiberoptic bronchoscope is a blind method, but we felt that combined with a variety of tools such as video laryngoscope, the success rate in intubation will increase.


Lumbar burner and stinger syndrome in an elderly athlete.
Burner or stinger syndrome is a rare sports injury caused by direct or indirect trauma during high-speed or contact sports mainly in young athletes. It affects peripheral nerves, plexus trunks or spinal nerve roots, causing paralysis, paresthesia and pain. We report the case of a 57-year-old male athlete suffering from burner syndrome related to a lumbar nerve root. He presented with prolonged pain and partial paralysis of the right leg after a skewed landing during the long jump. He was initially misdiagnosed since the first magnet resonance imaging was normal whereas electromyography showed denervation. The insurance company refused to pay damage claims. Partial recovery was achieved by pain medication and physiotherapy. Burner syndrome is an injury of physically active individuals of any age and may appear in the cervical and lumbar area. MRI may be normal due to the lack of complete nerve transection, but electromyography typically shows pathologic results.


Hospital-Acquired Infection in Pediatric Subjects With Congenital Heart Disease Postcardiotomy Supported on Extracorporeal Membrane Oxygenation.
To determine prevalence of and risk factors for infection in pediatric subjects with congenital heart disease status postcardiotomy supported on extracorporeal membrane oxygenation, as well as outcomes of these subjects. Retrospective cohort from the Extracorporeal Life Support Organization. U.S. and international medical centers providing care to children with congenital heart disease status postcardiotomy. Critically ill pediatric subjects less than 8 years old admitted to medical centers between January 1, 2013, and December 31, 2015, who underwent cardiac surgery for congenital heart disease and required extracorporeal membrane oxygenation support within the first 14 postoperative days. Subjects were excluded if they underwent orthotopic heart transplantation, required preoperative extracorporeal membrane oxygenation, and had more than one postoperative extracorporeal membrane oxygenation run. None. A total of 1,314 extracorporeal membrane oxygenation subject encounters in the Extracorporeal Life Support Organization registry met inclusion criteria. Neonates comprised 53% (n = 696) of the cohort, whereas infants made up 33% (n = 435). Of the 994 subjects with Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery categorizable surgery, 33% (n = 325) were in Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery category 4 and 23% (n = 231) in Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery category 5. While on extracorporeal membrane oxygenation, 229 subjects (17%) acquired one or more extracorporeal membrane oxygenation-related infections, which represents an occurrence rate of 67 infections per 1,000 extracorporeal membrane oxygenation days. Gram-negative (62%) and Gram-positive (42%) infections occurred most commonly. Forty percent had positive blood cultures. Infants and children were at higher infection risk compared with neonatal subjects; subjects undergoing less complex surgery had higher infection rates. Unadjusted survival to hospital discharge was lower in infected subjects compared with noninfected subjects (43% vs 51%; p = 0.01). After adjusting for confounders via propensity matching, we identified no significant mortality difference between infected and noninfected subjects. Neonatal and pediatric subjects in this study have a high rate of acquired infection. Infants and children were at higher infection risk compared with neonatal subjects. There was not, however, a significant association between extracorporeal membrane oxygenation-related infection and survival to hospital discharge after propensity matching.


Oral leiomyoma in retromolar trigone. A case report.
Leiomyomas are bening tumours originated on smooth muscle. The most frequent site of appearance are uterine myometrium, gastrointestinal tract and skin. The highest incidence occurs between 40 and 49 years of age. Its presentation is unusual in children or in older patients. Leiomyomas are unfrequent in the oral cavity, but in this location are usually localized on tongue, lips and palate. Leiomyomas use to appear as well-defined masses, with slow growth and totally asymptomatic. Pain is present just in rare cases. The treatment is surgical escision. Recurrences are extremely unfrequent. The diagnosis is mainly determined by histological studies due to its unspecific clinical appearance. Histopathologically proliferation of smooth muscle cells is observad without necrotic areas. A low number of mitotic figures can be seen. We present the case report of a 25-year old male patient, with a leiomioma on his right retromolar trigone. The low incidence of this pathology, the age of the patient and the unusual location, make the report of the case worthy.


Para-articular fusion of the proximal interphalangeal joint of the hand.
The para-articular procedure for the arthrodesis of an interphalangeal joint is more reliable, rapid and simpler than intra-articular fusion. The position is easily maintained, and therefore one has no difficulty with approximating the flexion and rotational angles. Since a large dead space is not produced in carrying out the procedure, use of a compressing force for adequate surface contact is not necessary. Shortening of the finger is not a hazard. A Kirschner wire is used in the technique described, which gives good protection for the graft and keeps the joint in the desired position without distracting the surfaces during the bony resorption at the joint.


Next generation sequencing and array-based comparative genomic hybridization for molecular diagnosis of pediatric endocrine disorders.
Next-generation sequencing (NGS) and array-based comparative genomic hybridization (array CGH) have enabled us to perform high-throughput mutation screening and genome-wide copy number analysis, respectively. These methods can be used for molecular diagnosis of pediatric endocrine disorders. NGS has determined the frequency and phenotypic variation of mutations in several disease-associated genes. Furthermore, whole exome analysis using NGS has successfully identified several novel causative genes for endocrine disorders. Array CGH is currently used as the standard procedure for molecular cytogenetic analysis. Array CGH can detect various submicroscopic genomic rearrangements involving exons or enhancers of disease-associated genes. This review introduces some examples of the use of NGS and array CGH for the molecular diagnosis of pediatric endocrine disorders.


Ensembl core software resources: storage and programmatic access for DNA sequence and genome annotation.
The Ensembl software resources are a stable infrastructure to store, access and manipulate genome assemblies and their functional annotations. The Ensembl 'Core' database and Application Programming Interface (API) was our first major piece of software infrastructure and remains at the centre of all of our genome resources. Since its initial design more than fifteen years ago, the number of publicly available genomic, transcriptomic and proteomic datasets has grown enormously, accelerated by continuous advances in DNA-sequencing technology. Initially intended to provide annotation for the reference human genome, we have extended our framework to support the genomes of all species as well as richer assembly models. Cross-referenced links to other informatics resources facilitate searching our database with a variety of popular identifiers such as UniProt and RefSeq. Our comprehensive and robust framework storing a large diversity of genome annotations in one location serves as a platform for other groups to generate and maintain their own tailored annotation. We welcome reuse and contributions: our databases and APIs are publicly available, all of our source code is released with a permissive Apache v2.0 licence at http://github.com/Ensembl and we have an active developer mailing list ( http://www.ensembl.org/info/about/contact/index.html ). http://www.ensembl.org.


[Acupoint puncture combined with Ilizarov technique for the treatment of elderly paitents with knee osteoarthritis].
To explore the clinical effect of acupoint puncture combined with Ilizarov technique in the treatment of knee osteoarthritis in the elderly. From March 2015 to February 2016, 76 patients with primary knee osteoarthritis were treated with tibial osteotomy acupoint puncture grouop and Ilizarov technique anatomical puncture group, including 24 males and 52 females, aged 56 to 75 years old with an average of 61.4 years old, and a course of 3 to 17 years with an average of 5.2 years. Among them, 38 cases were treated with external fixation of acupoint puncture needle and 38 cases were treated with external fixation of anatomical puncture needle. Preoperative full-length X-ray of both lower limbs showed tibial varus deformity, narrowing of medial knee joint space and enlargement of lateral knee joint space. The force line of the affected knee and lower limb was moved inward by body surface measurement, and the KSS knee function score was decreased. Symptoms included medial knee pain, flexion and extension, and conservative treatment for more than 2 years. The lower limb force lines of both groups were corrected and the osteotomy ends healed well. No nonunion of osteotomy, inadequate correction of lower limbs or recurrence of deformity were found. Seventy-five patients were followed up for 3, 6, 12 and 24 months after operation. There was no significant difference in knee joint mobility between the two groups before operation and on 6, 12, 24 months after operation(F=1.346, P>0.05). There were significant difference in KSS pain and total score between the two groups at 3 months after operation, acupoint puncture group was better than anatomical puncture group(P<0.05); there was no significant difference in KSS score at 12 months after operation(P>0.05). The acupoint puncture group formed a potential acupuncture effect in the acupoint area by continuously tightening the steel needle on Ilizarov ring external fixator during the post-operative adjustment. Within three months after wearing external fixator, the knee pain symptoms of knee osteoarthritis were relieved rapidly, continuously and effectively, which was significantly better than that of the anatomical puncture group.


Involvement of endoplasmic reticulum stress in regulation of endometrial stromal cell invasiveness: possible role in pathogenesis of endometriosis.
Endoplasmic reticulum (ER) stress is known to reduce invasiveness in some cancer cells by inhibiting the AKT/mTOR pathway. A previous study from our laboratory suggested that ER stress is promoted by progesterone in human endometrial cells, which suggests that progesterone may inhibit endometrial cell invasiveness by up-regulating ER stress. Therefore, aberrant ER stress in response to progesterone may contribute to the altered invasiveness found in endometriotic tissues. To test this hypothesis, we elucidate whether ER stress is involved in regulation of human endometrial cell invasiveness through the AKT/mTOR pathway and if this involvement is associated with altered invasiveness in endometriotic cells. Specifically, we sought to determine the effects of ER stress on AKT/mTOR pathway by evaluating ER stress-mediated CHOP/TRIB3 signaling, a negative regulator of AKT. We found that ER stress marker GRP78 expression increased with CHOP and TRIB3 expression in normal endometrial stromal cells (NESCs) treated with tunicamycin, and this increase was accompanied by decreased AKT and mTOR activity and cellular invasiveness. Similarly, progesterone increased GRP78, CHOP and TRIB3 expression in NESCs. Subsequently, inhibition of AKT and mTOR activity decreased cellular invasiveness. This progesterone-induced decrease in cellular invasiveness was reversed by inhibition of ER stress. In contrast, progesterone did not change CHOP, TRIB3, AKT, mTOR or invasiveness in endometriotic cyst stromal cells. In contrast to normal endometrium, endometriotic tissues showed no changes in CHOP, TRIB3 and invasion-related proteins (MMP2 and MMP9) expression throughout the menstrual cycle. Taken together, our findings indicate that abnormal ER stress response to progesterone increased endometriotic stromal cell invasiveness via the AKT/mTOR pathway.


1,25(OH)2D3/VDR attenuates high glucose‑induced epithelial‑mesenchymal transition in human peritoneal mesothelial cells via the TGFβ/Smad3 pathway.
Epithelial-mesenchymal transition (EMT) has been recognized to accelerate peritoneal membrane dysfunction. 1,25(OH)2D3/vitamin D receptor (VDR) is important for preventing various types of EMT in vivo. However, its function on EMT and inflammation of human peritoneal mesothelial cells (HPMCs) remains to be elucidated. Therefore, the present study investigated the effects of 1,25(OH)2D3/VDR on high glucose (HG)‑induced EMT and inflammation in HPMCs and the underlying molecular mechanism. It was determined that HG reduced VDR expression, increased inflammatory cytokine expression, including transforming growth factor β (TGFβ) and interleukin‑6 (IL‑6) and phosphorylated‑SMAD family member 3 (p‑Smad3) expression. EMT was promoted as the expression level of the epithelial marker E‑cadherin was reduced, whereas expression levels of the mesenchymal markers α‑SMA and FN were increased. 1,25(OH)2D3 pretreatment inhibited the expression of inflammatory cytokines in HPMCs and attenuated HG‑induced EMT, possibly through inhibition of the TGFβ/Smad pathway by binding to its receptor VDR.


House-dust mites and mattresses.
Despite considerable efforts to develop anti dust mite strategies, surprisingly few studies have evaluated the allergen content in different types of mattresses in everyday use. This study investigated the presence of mite feces (an indicator of mite allergens) in foam and spring mattresses. The homes of 152 schoolchildren in Northern Norway were investigated. Dust samples were collected in a standardized way from 24 foam mattresses without covers, 68 foam mattresses with covers, and 24 spring mattresses, and the presence of mite feces detected by a guanine colorimetric paper test (Acarex). We found mite feces in 15 (40.5%) of the dust samples from the foam mattresses without covers and 18 (26.3%) of the foam mattresses with covers. Only three (12.5%) of the spring mattresses contained detectable amounts of feces. Signs of dampness, age of mattress, cleaning of mattress, frequency of vacuuming the bedroom, mechanical ventilation, bedroom temperature and bedroom relative humidity were associated with the presence of mite feces. After adjustment for relevant confounders, the risk of finding mite feces was four times higher in foam compared to spring mattresses (odds ratio 4.0, 95% confidence interval (CI) 1.1-15.1), and eight times higher for the foam mattresses without cover (OR 8.1, 95% CI 1.8-36.9). A simple replacement of foam mattresses with spring mattresses may reduce the exposure to house-dust-mite allergens.


Angularly resolved polarization microscopy for birefringent materials with Fourier ptychography.
Polarization light microscopy is a very popular approach for structural imaging in optics. So far these methods mainly probe the sample at a fixed angle of illumination. They are consequently only sensitive to the polarization properties along the microscope optical axis. This paper presents a novel method to resolve angularly the polarization properties of birefringent materials, by retrieving quantitatively the spatial variation of their index ellipsoids. Since this method is based on Fourier ptychography microscopy the latter properties are retrieved with a spatial super-resolution factor. An adequate formalism for the Fourier ptychography forward model is introduced to cope with angularly resolved polarization properties. The inverse problem is solved using an unsupervised deep neural network approach that is proven efficient thanks to its performing regularization properties together with its automatic differentiation. Simulated results are reported showing the feasibility of the methods.


Evaluation of relationship between arterial and venous blood gas values in the patients with tricyclic antidepressant poisoning.
Determination of arterial blood gas (ABG) values is essential in the evaluation of patients with TCA poisoning. The relationship between arterial and venous blood gas pH has not been established in TCA poisoning. In TCA poisoning, blood vessels vasodilatation due to antidepressant-induced alpha-blockade and also metabolic acidosis may lead to arterialization of venous blood, which in turn enhances the relationship between ABG and VBG parameters. Therefore this study was designed to evaluate the relationship between ABG and VBG pH values in TCA poisoned patients. This prospective study was performed in the Poisoning Emergency Department of Noor Hospital, Isfahan, Iran. Samples for arterial and venous blood gas analysis were obtained during initial evaluation of TCA-poisoned patients and 30 min after treatment with sodium bicarbonate. The venous blood gas samples were collected with samples for other blood tests at the time of intravenous line insertion. Laboratory data were recorded on a database form initiated in the emergency department and analyzed by paired student t-test. The degree of agreement between the arterial and venous pH measurements was evaluated by Bland and Altman method. Data from 50 TCA-poisoned patients were analyzed. There were significant differences between mean differences of ABG and VBG parameter values on the initial evaluation. There was also a relationship between arterial and venous pH on the initial evaluation. In TCA poisoning, the peripheral venous pH measurement is a valid and reliable substitute for arterial pH.


New Diagnosis of Obstructive Sleep Apnea Following Anterior Cervical Discectomy Complicated by Rheumatoid Arthritis: A Case Report.
Obstructive sleep apnea (OSA) is the most common variant of sleep-disordered breathing that often goes undiagnosed. OSA is characterized mainly by anatomical obstruction or partial collapse of upper airways during sleep. The obstruction is multifactorial, and a lesser-known fact is that damage to the pharyngeal plexus during head and neck procedures or placement of hardware in the cervical area can lead to narrowing or collapse of the upper airway. We present such a case of a 59-year-old female who developed new-onset OSA after undergoing anterior cervical discectomy and fusion (ACDF). The severity of OSA worsened with the progression of her rheumatoid arthritis (RA) in the cervical region. This case report aims to raise awareness of such an association among clinicians to enable them to screen appropriate patients for sleep-disordered breathing and treat them accordingly.


Comparison of walking recommendations in previously inactive women.
To compare the number of steps accumulated by women instructed to walk 10,000 steps per day (10K group) with those told to take a brisk 30-min walk on most, preferably all, days of the week (30-min group). Daily steps were compared for 58 sedentary women (mean age 45.0+/-6.0 yr) randomly assigned to either the 10K or the 30-min group. Subjects wore a sealed pedometer for 2 wk for baseline physical activity assessment. Those averaging <or=7000 steps per day were randomly assigned to a group for the 4-wk intervention. All subjects wore a sealed pedometer capable of storing 7 d of data, and reported to the laboratory each week so that investigators could gather step counts. The 10K group wore a second pedometer for viewing their daily steps. There were no differences (P>0.05) between the groups for baseline steps. During the intervention, there was a significant difference (P<0.005) between groups in daily steps. The 30-min group walked 8270+/-354 steps per day, and the 10K group walked 10,159+/-292 steps per day. The 30-min group averaged 9505+/-326 steps per day on the days that a 30-min walk occurred, and 5597+/-363 steps per day when no walk occurred (P<0.05). The 10K group averaged 11,775+/-207 steps on days when they walked at least 10,000 steps, and 7780+/-231 steps on days that their target was not achieved (P<0.05). Women walk more when told to take 10,000 steps per day compared with those instructed to take a brisk 30-min walk. On days when women took a 30-min walk, their average step count was near 10,000.


Functional genomic diversity is correlated with neutral genomic diversity in populations of an endangered rattlesnake.
Theory predicts that genetic erosion in small, isolated populations of endangered species can be assessed using estimates of neutral genetic variation, yet this widely used approach has recently been questioned in the genomics era. Here, we leverage a chromosome-level genome assembly of an endangered rattlesnake (Sistrurus catenatus) combined with whole genome resequencing data (N = 110 individuals) to evaluate the relationship between levels of genome-wide neutral and functional diversity over historical and future timescales. As predicted, we found positive correlations between genome-wide estimates of neutral genetic diversity (π) and inferred levels of adaptive variation and an estimate of inbreeding mutation load, and a negative relationship between neutral diversity and an estimate of drift mutation load. However, these correlations were half as strong for projected future levels of neutral diversity based on contemporary effective population sizes. Broadly, our results confirm that estimates of neutral genetic diversity provide an accurate measure of genetic erosion in populations of a threatened vertebrate. They also provide nuance to the neutral-functional diversity controversy by suggesting that while these correlations exist, anthropogenetic impacts may have weakened these associations in the recent past and into the future.


Comparison of sequential, random, and hemacytometer methods for counting Cryptosporidium oocysts.
In animal and clinical studies of Cryptosporidium infection, counting Cryptosporidium oocysts in collected fecal samples is often critical to interpretation of results and validity of statistical analyses. In this experiment, 3 methods of counting oocysts derived from feces of infected mice were compared. These included sequential counting of oocysts in 25 adjacent microscopic fields, random counting of oocysts in 25 scattered microscopic fields, and hemacytometer counting of oocysts using standard procedures. Numerical results are expressed as the numbers of oocysts per microscopic field for sequential and random counting methods or per microliter for the hemacytometer method. Our results showed that the numbers of oocysts adjusted for volume and weight, or for volume alone, were similar for all 3 techniques. Linear relationships between the 3 methods allow use of linear regression to convert the number of oocysts counted by 1 method into those counted by another. This suggests that comparisons between different experiments in which Cryptosporidium oocysts are counted using any of these methods are both possible and valid.


Multi-cystic (rete testis) supernumerary testis in polyorchidism with underlying microlithiasis: ultrasound features.
Polyorchidism is a rare congenital anomaly, readily diagnosed on ultrasound. Testicular microlithiasis is a condition increasingly recognized and with a possible association with primary testicular malignancy. Rete testis has a variable appearance and is an unusual finding in the young patient. We describe the ultrasound appearances of the combination of polyorchidism, rete testis and microlithiasis, a combination that has not been previously reported.


Evaluation of cutaneous and proprioceptive sensation in children: a reliability study.
Forty-three healthy children aged between six and 12 years were tested to determine the intra-rater reliability of four clinical cutaneous and proprioceptive sensory assessment tools: touch pressure, vibration perception, thermal discrimination and kinaesthesis. The tests were carried out bilaterally on proximal and distal upper- and lower- extremity sites. The mean intraclass coefficients represented good to excellent reliability, which suggests that these assessment tools allow objective and reproducible measurements of cutaneous and proprioceptive sensation in children. The results were compared with existing data in the literature: in general, children and adults obtain similar sensory scores, and sex, age and laterality have no significant effect on the results for any test. However, the touch-pressure and vibration scores were significantly influenced by the site tested, the index fingerpad being the most sensitive area in both tests.


4-Quinolone alkaloids from Melochia odorata.
The methanol extract of Melochia odorata yielded three 4-quinolone alkaloids including waltherione A (1) and two new alkaloids, waltherione C (2) and waltherione D (3). Waltheriones A and C showed significant activities in an in vitro anti-HIV cytoprotection assay at concentrations of 56.2 and 0.84 μM and inhibition of HIV P24 formation of more than 50% at 1.7 and 0.95 μM, respectively. The structures of the alkaloids were established by spectroscopic data interpretation.


The "Moving Heart Program": an intervention to improve physical activity among patients with coronary heart disease.
this paper reports the results of a nursing-administered theory-based intervention, the "Moving Heart Program", based on the implementation intention theory and pointed at improving physical activity adherence among coronary heart disease outpatients in Brazil. this experimental study applied assessments at baseline, 1 and 2 months after baseline. The Consolidated Standards of Reporting Trials statement was followed. Participants were randomly assigned to intervention, comprising action and coping plans on how to deal with anticipated barriers (n=69), or a standard-care control group (n=67). participants submitted to the intervention showed significant higher levels of physical activity 2 months after baseline and were significantly more active than the control group. the results indicate that the intervention is feasible for patients with coronary heart disease and can be a useful tool to facilitate intended lifestyle changes. This study brings relevant contributions to the Nursing field and other health-related areas, once the intervention presents low cost to health services and can be applied in cardiac rehabilitation programs, showing significant benefits to participants.


Masked primes activate feature representations in reading aloud.
Theories of reading aloud are silent about the role of subphonemic/subsegmental representations in translating print to sound. However, there is empirical evidence suggesting that feature representations are activated in speech production and visual word recognition. In the present study, we sought to determine whether masked primes activate feature representations in reading aloud using a variation of the masked onset priming effect (MOPE). We found that target nonwords (e.g., BAF) were read aloud faster when preceded by masked nonword primes that shared their initial phoneme with the target (e.g., bez), or primes whose initial phoneme shared all features except voicing with the first phoneme of the target (e.g., piz), compared with unrelated primes (e.g., suz). We obtained the same result in 2 experiments that used different participants and prime durations (around 60 ms in Experiment 1 and 50 ms in Experiment 2). The significant masked feature priming effect that was observed in both experiments converges with the empirical evidence in the speech production and visual word recognition domains indicating a functional role for features in reading aloud. Our findings motivate the further development of current theories of reading aloud and have important implications for extant theories of speech production.


Radiofrequency ablation for pancreatobiliary disease: an updated review.
Endoscopic radiofrequency ablation (RFA) has emerged as a minimally invasive treatment option in cases of malignant biliary obstruction, pancreatic cancer, and other pancreatic cystic neoplasms. Intraductal biliary RFA is safe, effective, and confers a survival advantage over stenting alone, where it should be used an adjunct to biliary stenting. Endoscopic ultrasound-guided RFA can also provide pancreatic cyst resolution in patients who are not ideal operative candidates. The aim of this review is to describe the endoscopic applications and associated outcomes of RFA.


Unified treatment of scattering, absorption, and luminescence spectra from a plasmon-exciton hybrid by temporal coupled-mode theory.
Plasmonic nanostructures are capable of tailoring the emission of a nearby emitter by increasing (or reducing) the brightness, shortening (or prolonging) the lifetime, and shaping the spectrum. Experimental characterization of such coupled plasmon-exciton (plexciton) systems usually relies on the acquisition and comparison of scattering, absorption, or luminescence spectra. However, theoretical accounts of these optical spectra, which are key to distinguishing between the coupling regimes and to standardizing the coupling criteria, often scatters in different frameworks, varying from classical to quantum-mechanical. Therefore, developing a unified and simple formalism that can simultaneously compare all these spectral signatures in different coupling regimes is nontrivial. Here, we use a temporal coupled-mode formalism to reproduce the scattering, absorption, and luminescence spectra of a plexciton system and find that its luminescence reaches a maximum at a critical coupling point, featuring a light-emitting plexciton with intense brightness and ultrafast lifetime. This simple approach provides a unified and phenomenological treatment of these spectra by simply including or excluding an external driving term. It therefore allows for a direct comparison of different spectroscopic signatures from the plexciton system and provides an easy-to-use guidance for the design of broadband light-emitting devices.


Inference of common genetic network using fuzzy adaptive resonance theory associated matrix method.
Inferring genetic networks from gene expression data is the most challenging work in the post-genomic era. However, most studies tend to show their genetic network inference ability by using artificial data. Here, we developed the fuzzy adaptive resonance theory associated matrix (F-ART matrix) method to infer genetic networks and applied it to experimental time series data, which are gene expression profiles of Saccharomyces cerevisiae responding under oxidative stresses such as diamide, heat shock and H2O2. We preprocessed them using the fuzzy adaptive resonance theory and successfully identified genetic interactions by drawing a 2-dimensional matrix. The identified interactions between diamide and heat shock stress were confirmed to be the common interactions for two stresses, compared with the KEGG metabolic map, BRITE protein interaction map, and gene interaction data of other papers. In the predicted common genetic network, the hit ratio was 60% for the KEGG map. Several gene interactions were also drawn, which have been reported to be important in oxidative stress. This result suggests that F-ART matrix has the potential to function as a new method to extract the common genetic networks of two different stresses using experimental time series microarray data.


The chicken or the egg? A meta-analysis of panel studies of the relationship between work-family conflict and strain.
Does work-family conflict predict strain, does strain predict work-family conflict, or are they reciprocally related? To answer these questions, we used meta-analytic path analyses on 33 studies that had repeatedly measured work interference with family (WIF) or family interference with work (FIW) and strain. Additionally, this study sheds light on whether relationships between WIF/FIW and work-specific strain support the popular cross-domain perspective or the less popular matching perspective. Results showed reciprocal effects; that is, that WIF predicted strain (β = .08) and strain predicted WIF (β = .08). Similarly, FIW and strain were reciprocally related, such that FIW predicted strain (β = .03) and strain predicted FIW (β = .05). These findings held for both men and women and for different time lags between the 2 measurement waves. WIF had a stronger effect on work-specific strain than did FIW, supporting the matching hypothesis rather than the cross-domain perspective.


The role of inorganic nitrate and nitrite in CVD.
CVD is the leading cause of death worldwide, a consequence of mostly poor lifestyle and dietary behaviours. Although whole fruit and vegetable consumption has been consistently shown to reduce CVD risk, the exact protective constituents of these foods are yet to be clearly identified. A recent and biologically plausible hypothesis supporting the cardioprotective effects of vegetables has been linked to their inorganic nitrate content. Approximately 60-80 % inorganic nitrate exposure in the human diet is contributed by vegetable consumption. Although inorganic nitrate is a relatively stable molecule, under specific conditions it can be metabolised in the body to produce NO via the newly discovered nitrate-nitrite-NO pathway. NO is a major signalling molecule in the human body, and has a key role in maintaining vascular tone, smooth muscle cell proliferation, platelet activity and inflammation. Currently, there is accumulating evidence demonstrating that inorganic nitrate can lead to lower blood pressure and improved vascular compliance in humans. The aim of this review is to present an informative, balanced and critical review of the current evidence investigating the role of inorganic nitrate and nitrite in the development, prevention and/or treatment of CVD. Although there is evidence supporting short-term inorganic nitrate intakes for reduced blood pressure, there is a severe lack of research examining the role of long-term nitrate intakes in the treatment and/or prevention of hard CVD outcomes, such as myocardial infarction and cardiovascular mortality. Epidemiological evidence is needed in this field to justify continued research efforts.


Incompatibility for or pre-immunization against M1s determinants decreases lethal graft-versus-host reaction developed across non-H-2 and/or H-2 barriers.
The effect of incompatibility for M1s determinants was studied in lethal graft-versus-host reaction (GVHR) in the mouse. GVHR was induced in adult recipients of the following H-2k strains: (AKR x B10.BR)F1 (Mlsa/Mlsb); (C3H x B10.BR)F1 (Mlsc/Mlsb); (CBA/J x B10.BR)F1 (Mlsd/Mlsb) and (CBA/H x B10. BR)F1 (Mlsb). Recipient mice were heavily irradiated and grafted with bone marrow and spleen cells from H-2 compatible B10.BR (H-2k, Mlsb) or H-2 incompatible B10.D2 (H-2d, Mlsb) or B10 (H-2b, Mlsb) strains. The cells from B10.D2 and B10 donors were normal, while those from B10.BR donors were either normal or pre-immunized against the recipient strains. In all experiments the survival of recipients with Mlsa/Mlsb and Mlsd/Mlsb phenotypes, and only in one experiment of those with Mlsc/Mlsb phenotype was greater and/or the survival time longer than that of recipients expressing only Mlsb. However, late deaths (greater than 120 days post grafting) observed after grafting of normal B10.BR cells were more frequent in Mlsd/Mlsb than in Mlsb strains. On the other hand, when B10.BR donor cells were pre-immunized against H-2k compatible (AKR x B10.BR)F1 (Mlsa/Mlsb) or (CBA/J x B10.BR)F1 (Mlsd/Mlsb) strains, the survival time of H-2 incompatible (B10 x B10.BR)F1 (H-2b/k, Mlsb) recipients was longer than when donor cells were pre-immunized against (CBA/H x B10-BR)F1 (Mlsb) strain. We conclude that donor incompatibility for Mlsa or Mlsd or donor-pre-immunization against Mlsa or Mlsd exerts a protective effect on lethal GVHR developed across non-H-2 or H-2 barriers; the protective effect of Mlsc is less efficient or absent. The Mls-induced protective effect shows the following properties: (a) efficiency in vivo correlates with the capacity of the corresponding alleles to stimulate an in vitro MLR; (b) is efficient in either primary or secondary response to other minor antigens; (c) is not H-2 restricted; (d) is nonspecific; (e) disappears late after grafting; (f) with respect to the genetic background, the early protective effect is followed, late after grafting, by an opposite effect which increases the mortality, suggesting that Mls locus determinants are capable of activating several cell populations with different biological functions.


Genome-scale data reveal that endemic Poecilia populations from small sulphidic springs display no evidence of inbreeding.
Populations with limited ranges can be highly vulnerable to changes in their environment and are, thus, of high conservation concern. Populations that experience human-induced range reductions are often highly inbred and lack genetic diversity, but it is unknown whether this is also the case for populations with naturally small ranges. The fishes Poecilia sulphuraria (listed as critically endangered) and Poecilia thermalis, which are endemic to small hydrogen sulphide-rich springs in southern Mexico, are examples of such populations with inherently small habitats. We used geometric morphometrics and population genetics to quantify phenotypic and genetic variation within and among two populations of P. sulphuraria and one population of P. thermalis. Principal component analyses revealed phenotypic and genetic differences among the populations. Evidence for inbreeding was low compared to populations that have undergone habitat reduction. The genetic data were also used to infer the demographic history of these populations to obtain estimates for effective population sizes and migration rates. Effective population sizes were large given the small habitats of these populations. Our results imply that these three endemic extremophile populations should each be considered separately for conservation purposes. Additionally, this study suggests that populations in naturally small habitats may have lower rates of inbreeding and higher genetic diversity than expected, and therefore may be better equipped to handle environmental perturbations than anticipated. We caution, however, that the inferred lack of inbreeding and the large effective population sizes could potentially be a result of colonization by genetically diverse ancestors.


[Effects of UV-A on pig skin].
The effects of high and progressive doses of UVA are studied on skin, from a clinical and microscopic, both optic and electronic, point of view. We use pigskin as pattern, due to its similarity to human skin and a PUVA 200 Waldman as source of radiation.


Removal of oxytetracycline and determining its biosorption properties on aerobic granular sludge.
This study investigates biosorption of Oxytetracycline, a broad-spectrum antibiotic, using aerobic granular sludge as an adsorbent in aqueous solutions. A sequencing batch reactor fed by a synthetic wastewater was operated to create aerobic granular sludge. Primarily, the pore structure and surface area of granular sludge, the chemical structure and the molecular sizes of the pharmaceutical, operating conditions, such as pH, stirring rate, initial concentration of Oxytetracycline, during adsorption process was verified. Subsequently, thermodynamic and kinetic aspects of the adsorption were examined and adsorption isotherm studies were carried out. It was shown that the aerobic granular sludge was a good alternative for biosorption of this pharmaceutical. The pharmaceutical was adsorbed better at pH values of 6-8. The adsorption efficiency increased with rising ionic strength. Also, it was seen that the adsorption process was an exothermic process in terms of thermodynamics. The adsorption can be well explained by Langmuir isotherm model.


[Influence of geomagnetic storms on the balance of autonomic regulatory mechanisms].
The investigation aimed to evaluate autonomic regulatory mechanisms in practically healthy persons during the geomagnetically quiet periods and during geomagnetic storms. The examinations were conducted among the volunteer young men (n=64) 18-22 years of age. The autonomic function was studied on the basis of the heart rate variability. The geomagnetically quiet periods were considered when the value of the K-index was no more then 2 and a geomagnetic storm was considered when the value of the index was 5 and more. It is ascertained that in the both cases the basic statistical indices of the heart rate were identical. The analysis of R-R intervals spectral power gave the possibility to sort the persons examined into the three different groups. The data obtained allowed to suggest that geomagnetic storms influence human organisms through the vagus centers by means of their excitation. This phenomenon may be considered as a self-regulatory physiologic mechanism of the adaptive character. The analysis of the spectral power of R-R intervals may be considered as a sensitive method for the detection of the magnitolabile persons.


Bounds on Identification of Genome Evolution Pacemakers.
Several studies have pointed out that the tight correlation between genes' evolutionary rate is better explained by a model denoted as the Universal PaceMaker (UPM) rather than by a simple rate constancy as manifested by the classical hypothesis of molecular clock (MC). Under UPM, each gene is associated with a single pacemaker (PM) and varies its evolutionary rate according to this PM ticks. Hence, the relative rates of all genes associated with the same PM remain nearly constant, whereas the absolute rates can change arbitrarily according to the PM ticks. A consequent question to that mentioned is finding the gene-PM association only from the gene sequence data. This, however, turns to be a nontrivial task and is affected by the number of variables, their random noise, and the amount of available information. To this end, a clustering heuristic was devised by exploiting the correlation between corresponding edge lengths across thousands of gene trees. Nevertheless, no theoretical study linking the relationship between the affecting parameters was done. We here study this question by providing theoretical bounds, expressed by the system parameters, on probabilities for positive and negative results. We corroborate these results by a simulation study that reveals the critical role of the variances.


Conceptual principles of quality of life: an empirical exploration.
Quality of life is a popular measure of outcomes and its widespread use has led to recent calls for a better understanding of the construct, emphasizing the need to build a substantial body of knowledge around what determines perceptions of life quality. Three widely reported and used conceptual principles are examined in this study. Self-ratings of life quality and three likely determinants at an individual level (stress), an interactional level (social support) and a community level (neighbourhood belonging) were used. The study involved two groups of young adults from an urban community, one identified as having an intellectual disability (ID). RESULTS Young adults with ID rated their satisfaction with health significantly higher and intimacy and community involvement lower than the comparison group. Social support emerged as the strongest predictor of life satisfaction across both groups. The conceptual principles of subjective quality of life provide a useful framework to discuss findings and to stimulate further research.


First record of ostracods as natural intermediate hosts of Anguillicola crassus, a pathogenic swimbladder parasite of eels Anguilla spp.
The ostracod Physocypria nipponica (Ostracoda: Candonidae) was found (prevalence 14.2%) to be the only intermediate host of the nematode Anguillicola crassus (Nematoda: Anguillicolidae), a pathogenic swimbladder parasite of eels, in a greenhouse-heated culture pond at Isshiki, Aichi Prefecture, Japan. Japanese eels Anguilla japonica from the same pond were found to be infected by adult A. crassus (prevalence 71.8%, intensity 1 to 6). This indicates that A. crassus could complete its life cycle under conditions of modern eel-culture technology where copepods were absent due to the unfavorable water quality for them, by utilizing ostracods as the intermediate host.


Nutritional, Physicochemical, and Organoleptic Properties of Camel Meat Burger Incorporating Unpollinated Barhi Date Fruit Pulp.
The chemical composition of unpollinated Barhi date fruit (UBDF) (at khalal maturity stage) pulp and its effect as fiber source or fat replacer on the quality characteristics of camel meat burgers were investigated. The UBDF was characterized by high total carbohydrate, fiber, and mineral contents. It contains substantial amounts of fiber (19.60%) and low-fat content. Prepared UBDF pulp was added to camel meat burger as a fiber source at 2.5, 5, 7.5, 10, and 15% instead of camel meat and as a fat replacer at 50, 75, and 100% instead of camel-back fat during manufacturing of camel meat burgers. Chemical composition, mineral content, instrumental color, cooking characteristics, and organoleptic properties were evaluated. Results indicated that adding UBDF as fiber source significantly reduced moisture and protein contents and increased total carbohydrates, including fiber content. In camel meat burgers, K and Ca significantly increased in UBDF level-dependent manure. Adding UBDF as a fat replacer significantly increased moisture and total carbohydrate contents, while a significant reduction in fat content has been remarked. Increasing the levels of UBDF pulp as either fiber source or fat replacer in camel burgers improved (p < 0.05) shrinkage, cooking loss, and cooking yield in roasted camel burger level-dependent manure. The incorporation of UBDF pulp in camel burgers increased the lightness (L ∗) values and decreased the redness (a ∗) and yellowness (b ∗) significantly. The formulated camel burgers with different UBDF pulp levels revealed better organoleptic characteristics than normal camel meat burgers. Interestingly, adding UBDF as fiber source at 7.5-15% presented overall acceptability of more than 90% compared to the control sample of 81.7%. In the same context, adding UBDF as a fat replacer at 100% replacing the level of added fats scored overall acceptability of more than 93.60% compared to the control sample of 67.4%. Generally, according to the results of this study, it could be concluded that UBDF pulp could be used as a functional additive to produce high-fiber and/or low-fat camel meat burgers.


The relationship between dioxin-like polychlorobiphenyls and IGF-I serum levels in healthy adults: evidence from a cross-sectional study.
Insulin-like growth factor I (IGF-I) and dioxin-like polychlorobiphenyls (DL-PCBs) have been associated with the pathogenesis of several diseases like cancer, diabetes and growth disorders. Because it has been suggested that organohalogenated contaminants could influence IGF-I levels in adults, the potential relationship between DL-PCBs and IGF-I serum levels was studied in 456 healthy adults from a representative sample of the general population of the Canary Islands (Spain). Free circulating serum levels of IGF-I and IGFBP-3 were measured through an ELISA methodology, while the serum levels of the 12 DL-PCBs congeners (IUPAC numbers # 77, 81, 105, 114, 118, 123, 126, 156, 157, 167, 169, and 189) were measured by gas chromatography/mass spectrometry (GC-MS). DL-PCBs 156 and 167, Total DL-PCBs body burden (∑PCBs: sum over the 12 measured DL-PCBs), and Total toxic burden (in terms of toxic equivalence to dioxins: ∑TEQs) showed a trend of inverse association with IGF-I serum levels in the whole studied population. After adjusting for potential confounders, including gender, body mass index (BMI), age, and IGF-binding protein-3 (IGFBP-3), younger (18-45 years) women with lower BMI (<27 kg/m(2)) and detectable levels of DL-PCB-156 showed significantly lower IGF-I levels than those in the same age and BMI subgroup with non-detectable levels of DL-PCB-156 (p<0.001). Similarly, ∑PCBs and ∑TEQs showed a tendency to an inverse association with IGF-I levels in the same group of women (p=0.017 and p=0.019 respectively). These findings suggest that DL-PCBs could be involved in the regulation of the IGF-system in a way possibly influenced by gender, age and BMI. Although these results should be interpreted with caution, such circumstances could contribute to explain the development of diseases associated to the IGF system.


Proteomics of Campylobacter jejuni Growth in Deoxycholate Reveals Cj0025c as a Cystine Transport Protein Required for Wild-type Human Infection Phenotypes.
Campylobacter jejuni is a major cause of food-borne gastroenteritis. Proteomics by label-based two-dimensional liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) identified proteins associated with growth in 0.1% sodium deoxycholate (DOC, a component of gut bile salts), and system-wide validation was performed by data-independent acquisition (DIA-SWATH-MS). LC-MS/MS quantified 1326 proteins (∼82% of the predicted C. jejuni proteome), of which 1104 were validated in additional biological replicates by DIA-SWATH-MS. DOC resulted in a profound proteome shift with 512 proteins showing significantly altered abundance. Induced proteins were associated with flagellar motility and antibiotic resistance; and these correlated with increased DOC motility and resistance to polymyxin B and ciprofloxacin. DOC also increased human Caco-2 cell adherence and invasion. Abundances of proteins involved in nutrient transport were altered by DOC and aligned with intracellular changes to their respective carbon sources. DOC increased intracellular levels of sulfur-containing amino acids (cysteine and methionine) and the dipeptide cystine (Cys-Cys), which also correlated with reduced resistance to oxidative stress. A DOC induced transport protein was Cj0025c, which has sequence similarity to bacterial Cys-Cys transporters. Deletion of cj0025c (Δcj0025c) resulted in proteome changes consistent with sulfur starvation, as well as attenuated invasion, reduced motility, atypical morphology, increased antimicrobial susceptibility and poor biofilm formation. Targeted metabolomics showed Δcj0025c could use known C. jejuni amino and organic acid substrates commensurate with wild-type. Medium Cys-Cys levels however, were maintained in Δcj0025c relative to wild-type. A toxic Cys-Cys mimic (selenocystine) inhibited wild-type growth, but not Δcj0025c Provision of an alternate sulfur source (2 mm thiosulfate) restored Δcj0025c motility. Our data confirm that Cj0025c is a Cys-Cys transporter that we have named TcyP consistent with the nomenclature of homologous proteins in other species.


THE FRESHWATER CYANOBACTERIUM PLANKTOTHRIX SP. FP1: MOLECULAR IDENTIFICATION AND DETECTION OF PARALYTIC SHELLFISH POISONING TOXINS.
A filamentous cyanobacterium, belonging to the Order of Oscillatoriales, was found to be responsible for a toxic algal bloom in Lake Varese, Italy, during the summer of 1997. Morphological characters, as well as near complete 16S rRNA gene sequencing, revealed that the dominant species of the bloom was most closely related to the genus Planktothrix. In addition, genetic analysis of the phycocyanin operon of Planktothrix sp. FP1 revealed a novel primary structure, previously undescribed within the cyanobacteria, which was used as a genetic marker for rapid detection and identification of this toxic strain. The occurrence of saxitoxin (STX), a principal toxin in paralytic shellfish poisoning (PSP), was confirmed in the natural bloom sample by both pre-column and post-column derivatization high-performance liquid chromatography (HPLC) analyses, and eventually by liquid chromatography/mass spectrometry (LC/MS). The toxicity of this field sample was also revealed by electrophysiological assays in which the extract inhibited 90% of the voltage-dependent Na+ current in human neuroblastoma cells at the STX concentration of 80 nM. The cultured strain showed a lower physiologic activity than the bloom sample (67% blockage of Na+ current at a toxin concentration of 200 nM), and STX was detected only by pre-column HPLC, indicating the presence of a compound structurally close to STX. Chemical and molecular genetic analyses performed here add Planktothrix sp. FP1 to the growing list of diverse cyanobacterial species capable of synthesizing STX and its related compounds.


Fish under pressure: Examining behavioural responses of Iberian barbel under simulated hydropeaking with instream structures.
Hydropeaking is the rapid change in the water flow downstream of a hydropower plant, driven by changes in daily electricity demand. These fluctuations may produce negative effects in freshwater fish. To minimize these impacts, previous studies have proposed habitat enhancement structures as potential mitigation measures for salmonids. However, the recommendation of these mitigation measures for cyprinids remains scarce and their effects unknown. In this study, the effects of potential habitat mitigation structures under simulated hydropeaking and base-flow conditions are examined for Iberian barbel (Luciobarbus bocagei) in an indoor flume. Solid triangular pyramids and v-shaped structures were evaluated as potential flow-refuging areas and compared with a configuration without structures. A novel, interdisciplinary approach is applied to investigate individual and group responses to rapidly changing flows, by assessing physiological (glucose and lactate), movement behaviour (structure use, sprints and drifts) and the pressure distribution using a fish-inspired artificial lateral line flow sensor. The major findings of this study are four-fold: 1) Under hydropeaking conditions, the v-shaped structures triggered a lactate response and stimulated individual structure use, whereas solid structures did not elicit physiological adjustments and favoured individual and group structure use. Overall, both solid structures and their absence stimulated sprints and drifts. 2) The hydrodynamic conditions created in hydropeaking did not always reflect increased physiological responses or swimming activity. 3) Each event-structure combination resulted in unique hydrodynamic conditions which were reflected in the different fish responses. 4) The most relevant flow variable measured was the pressure asymmetry, which is caused by the vortex size and shedding frequency of the structures. Considering the non-uniform nature of hydropeaking events, and the observation that the fish responded differently to specific flow event-structure combinations, a diverse set of instream structures should be considered for habitat-based hydropeaking mitigation measures for Iberian barbel.


LIGHTCURVE ANALYSIS OF HILDA ASTEROIDS AT THE CENTER FOR SOLAR SYSTEM STUDIES: 2018 SEPTEBER - 2019 SEPTEMBER.
CCD photometric observations of three Hilda asteroids were made at the Center for Solar System Studies (CS3) in 2019 September. Analysis of the 2019 data for 4495 Dassanowsky, a reported binary (Warner and Stephens, 2019), found three periods, one being very long (431 h). The long period and a secondary one made it a potential member of the very wide binary asteroids but, for the first time for a member of this class, a third period seems to be present. A review of the 2018 data set using comparison star magnitudes from the ATLAS catalog (Tonry et al., 2018) found the previously unnoticed very long period. The secondary and tertiary periods were still in good agreement with the original two-period solution found in 2018. Though the odds are remote and considerable more data are required, the new results from the 2018 data are encouraging in the on-going effort to find evidence that validates claims of the existence of the very wide binary asteroid class.


Growth factors in the therapy of myelodysplasia: biological aspects.
Growth factors (GF) are reported to play an important role in the therapy of myelodisplastic syndromes (MDS). After in vitro administration a consistent group of MDS may respond to GF but the possibility of differentiation, regulation or expansion of myelodisplastic clones following GF therapy is still a question to be answered as their optimum dose and combinations. To validate if in vivo treatment with GF, may promote the regulation or the recovery of myelopoiesis and/or modify the clonality of the responses, we gave G-CSF after intensive chemotherapy in high risk MDS and acute leukemia evolving from MDS patients. According to our data the use of G-CSF after intensive chemotherapy may improve the CR rate without increase of leukemic transformation. However the answer were clonal and the remission duration remained very short so we suggest to utilize this time to perform other therapeutic strategies such as, when possible, the BMT.


Clinical Development Units (Nursing): the western Sydney approach.
On 24 September 1997 Western Sydney Area Health Service and the University of Western Sydney, Nepean (Australia) launched a network of nine Clinical Development Units (Nursing). The approach taken towards the development of CDU(N)s in western Sydney differs substantially from those taken elsewhere in terms of preparation for CDU(N) leadership and the role of CDU(N) criteria in the designation ('accreditation') process. The rationale underpinning the western Sydney approach, together with details of a leadership preparation programme, are discussed.