Conscious and unconscious perseverative cognition: is a large part of prolonged physiological activity due to unconscious stress?
Prolonged physiological activity is believed to be a key factor mediating between stress and later disease outcomes. Few studies, however, have investigated the crucial psychological factors that cause prolonged activity. This article proposes that conscious as well as unconscious perseverative cognition are the critical factors. Perseverative cognition indicates repetitive or sustained activation of cognitive representations of past stressful events or feared events in the future. In daily life, most prolonged physiological activity is not due to stressful events but to perseverative cognition about them. We and others have already found evidence that conscious perseverative cognition, i.e., worry, has physiological effects, in both laboratory and real life settings, and that perseverative cognition mediates prolonged responses to stressful events. Yet, there are convincing reasons to expect that unconscious perseverative cognition has an even larger role in stress-related prolonged activity. Firstly, since the greater part of cognitive processing operates without awareness, a considerable part of perseverative cognition is likely to be unconscious too. People may not be aware of most of their stress-related cognitive processes. Secondly, our recent studies have shown that increased activity of the autonomic nervous system continues after conscious perseverative cognition has stopped: It goes on for several hours and even during sleep. This and several other findings suggest that a considerable part of increased physiological activity may be due to unconscious perseverative cognition. The article closes with suggesting methods to test unconscious perseverative cognition and ways to change it, and concludes with stating that the notion of unconscious perseverative cognition potentially opens an entirely new area within stress research.


[Changes in the proliferative activity of cells from lymphoid organs of tumor-bearing mice after immunization with antitumoral vaccines].
The level of proliferative activity is studied in the cells of thymus, spleen and lymphoid nodes of mice with transplanted OH-2 tumour once- or thrice-immunized with vaccines from syngeneic tumour cells. Single immunization is shown to induce the short-term modulation of the proliferative processes in lymphoid organs and to increase somewhat the level of antitumour resistance of vaccinized mice. The triple-inoculation of vaccines evokes a more pronounced rise in the level of the proliferative activity in cells of lymphoid organs.


Trends in estimated intramammary antimicrobial usage in the Irish dairy industry from 2003 to 2019.
The objective of this study is to update earlier work on intramammary (IM) antimicrobial (AM) usage in Ireland. There is a need to measure AM usage in food-producing animals given increasing societal concerns about AM resistance as well as recent regulatory changes that dictate changes in how AM are used in food-producing animals and how AM sales and usage are recorded. National sales data were collected and used in this analysis. Sales of the number of IM AM tubes and amount of active ingredient sold were analyzed each year by product type [in-lactation (LC) therapy and dry cow (DC) therapy] and classification system (World Health Organization and more recent European Medicine Agency). Descriptive trends in estimated IM AM use are presented, including defined course dose (DCDvet; a technical unit for on-farm usage). There has been a decrease in estimated on-farm usage of IM AM during lactation, from 0.48 DCDvet/cow per year in 2015 to 0.43 DCDvet/cow per year in 2019. Almost all LC therapies sold include critically important AM (CIA), with 98% of the total DCDvet administered for LC therapy in 2019 containing at least 1 CIA. There has been a slow increase in tubes containing at least 1 highest priority CIA in LC therapies, from 0.01 DCDvet/cow per year in 2003, accounting for 2% of the total DCDvet administered for LC therapy, to 0.03 DCDvet/cow per year in 2019, accounting for 7% of the total DCDvet administered for LC use. The estimated usage of IM AM DC therapy has decreased from 1.09 DCDvet/cow per year in 2015 to 0.95 DCDvet/cow per year in 2019. In the last 5 yr, more than 40% of the total DC DCDvet administered contained at least 1 CIA, and there has been an increase in recent years in the percentage of the total DC DCDvet administered that contains at least 1 highest priority CIA, driven mainly by use of fourth-generation cephalosporin. This work provides further insights into IM AM usage in Ireland and highlights some important areas for attention, including availability of farm-level usage data, prescribing practices, and usage of important AM.


Membrane currents in a developing parasympathetic ganglion.
It is reported that chick embryo ciliary ganglion neurons that have just terminated their migration and are in the process of forming a ganglion express several properties underlying membrane excitability. Evidence is presented which suggests that these cells possess voltage-dependent sodium, potassium, and calcium currents as well as a calcium-activated potassium current. These currents resemble those previously described in the more mature ciliary ganglion (Bader, C. R., Bertrand, D., and Kato, A. C. (1982). Dev. Biol. 94, 131-141) but may differ in their density per unit membrane surface. For example, the density per unit surface of the voltage dependent sodium current in younger neurons appears to be 5 to 10 times smaller than in more mature neurons.


Oxidative modification of proteins: oxidation of tryptophan and production of dityrosine in purified proteins using Fenton's system.
Specific features of metal-catalyzed oxidation (MCO) of purified proteins (human serum albumin and human erythrocyte superoxide dismutase) were analyzed by the oxidation level of tryptophan and tyrosine. The production of dityrosine cross-links and the oxidation of tryptophan residues were recorded by fluorescence. The degree of oxidative modification of the amino acid residues of the proteins depended on the concentration of the Fenton's medium components and on the incubation time. These changes were different in different proteins. By electrophoresis and gel-permeation chromatography, changes in the superoxide dismutase structure are shown to be caused by oxidative modification of the enzyme and to be accompanied by a decrease in its activity. Findings with OH* scavengers (mannitol and ethanol) suggest that oxidative modification of the proteins in Fenton's medium should be associated not only with hydroxyl radical but also with ferryl and perferryl ions and with the radical CO(-.)(3).


Use of selectively trypsinized nucleosome core particles to analyze the role of the histone "tails" in the stabilization of the nucleosome.
Using immobilized trypsin and an appropriate fractionation procedure, we have been able to prepare, for the first time, nucleosome core particles containing selectively trypsinized histone domains. The particles thus obtained: [(H3T-H4T)2-2(H2AT-H2BT)].DNA; [(H3-H4)2-2(H2AT-H2BT)].DNA; [H3T-H4T)2-2(H2A-H2B)].DNA (where T means trypsinized), together with the non-trypsinized controls have been characterized using the following techniques: analytical ultracentrifugation, circular dichroism, thermal denaturation and DNAse I digestion. The major aim of this study was to analyze the role of the amino-terminal regions (the histone "tails") on the stability of the nucleosome in solution. The data obtained from this analysis clearly show that stability of the nucleosome core particle to dissociation (below a salt concentration of 0.7 M-NaCl) is not affected by the presence or the absence of any of the N-terminal regions of the histones. Furthermore, these histone regions make very little contribution, if any, to the conformational transition that nucleosomes undergo in this range of salt concentrations. They play, however, a very important role in determining the thermal stability of the particle, as reflected in the dramatic alterations exhibited by the melting profiles upon selective removal of these tails by trypsinization. The melting data can be explained by a simple hypothesis that ascribes interaction of H2A/H2B and H3/H4 tails to particular regions of the nucleosomal DNA.


Effect of CYP2D6*10 on pharmacokinetic variability of routinely administered metoprolol in middle-aged and elderly Japanese patients.
This study was performed to evaluate the effect of mutant alleles CYP2D6*2 and CYP2D6*10 on the pharmacokinetics of routinely administered metoprolol in middle-aged and elderly Japanese patients. We determined the genotypes of CYP2D6 in 34 patients aged from 56 years to 83 years, and analyzed the plasma concentration of metoprolol at steady state after repetitive administration. The pharmacokinetic parameters of metoprolol in individual patients were obtained from population estimates according to Bayes' theorem. The plasma concentrations of metoprolol in the patients with CYP2D6*1/*1 (group 1a) were similar to those in the patients with CYP2D6*1/*2 (group 1b). The plasma concentrations in the patients with CYP2D6*1/*10 (group 2a) were also similar to those in the patients with CYP2D6*2/*10 (group 2b) but were higher than those in group 1 (group 1a plus 1b). The plasma concentrations of metoprolol in the patients with CYP2D6*10/*10 (group 3) were significantly higher than those in group 1 and group 2 (group 2a plus 2b). Mean values of oral clearance (in l/h/kg) in Groups 1, 2, and 3 were estimated to be 1.2, 1.0, and 0.49, respectively. These oral clearance values of metoprolol estimated in middle-aged and elderly Japanese patients were lower than those estimated in healthy young Chinese reported previously. The present study indicated that CYP2D6*10 is mainly responsible for the large pharmacokinetic variability of routinely administered metoprolol in middle-aged and elderly Japanese patients. In addition, the pharmacokinetics of repetitively administered metoprolol in middle-aged and elderly patients may be different from that of a single dose in younger patients. These results suggested that a lower dose of metoprolol may be used in middle-aged and elderly patients with CYP2D6*10.


Prognostic significance of synaptophysin in stage I of squamous carcinoma and adenocarcinoma of the lung.
The prognostic significance of the presence of a neuroendocrine marker (synaptophysin, SY) was analyzed in stage I of squamous carcinoma and adenocarcinoma of the lung. A multicentric retrospective study was conducted with immunohistochemical staining in a single center of 318 patients resected for squamous carcinoma or adenocarcinoma in pathologic stage I. In all, 162 cases of squamous carcinoma and 156 cases of adenocarcinoma were identified, which included 105 patients in stage IA (50 patients with squamous carcinoma and 55 patients with adenocarcinoma) and 213 in stage IB (112 with squamous carcinoma and 101 with adenocarcinoma). Eighty-six tumors showed a presence of SY+ (27%). Univariate analysis showed lower survival rates at 5 years for those patients older than 70 years of age compared with those patients younger than 70 years of age (60.35% vs 70.57%; P = .007) and for those patients with SY+ compared with those with SY- (52.48% vs 72.68%; P = .0017). Patients with SY+ tumors showed a higher rate of recurrence than patients with SY- tumors (50% vs 33.6%; P = .008). Multivariate analysis showed that those patients greater that 70 years of age (hazard ratio [HR], 1.74; 95% confidence interval [CI], 1.14-2.65) and the presence of SY (HR, 2.15; 95% CI, 1.40-3.30) were significant independent prognostic factors associated with a poor outcome. Stage I of squamous carcinoma and adenocarcinoma of the lung with SY+ has a poor prognosis, with a higher frequency of recurrence and lower survival rates.


Decolorization of C.I. Reactive Red 2 by catalytic ozonation processes.
This study adopted O3, UV/TiO2/O3, O3/Mn(II) and O3/MnO2 systems to assess the decolorization efficiency of C.I. Reactive Red 2 (RR2). The decolorization rate increased with concentrations of Mn(II) and MnO2 in the ranges 0.05-0.1 and 0.05-0.8 g/l, respectively. However, when 0.5-3g/l TiO2 was added, the effect of TiO2 dosage for RR2 decolorization was insignificant in the UV/TiO2/O3 system. At pH 2, the decolorization rate constants of O3, O3/Mn(II) (0.05 g/l), O3/Mn(II) (0.1g/l), O3/Mn(II) (0.15 g/l), O3/MnO2 (0.05 g/l) and O3/MnO2 (0.8 g/l) were 0.816, 2.001, 3.173, 3.087, 1.040 and 1.648 min(-1), respectively. After 5 min of reaction, the decolorization rates followed the order O3/Mn(II)>O3/MnO2>O3>UV/TiO2/O3; however, the TOC removal did not vary among these systems. Adding ethanol reduced the decolorization rate of the UV/TiO2/O3 and O3/MnO2 systems and did not affect the decolorization rate of O3/Mn(II). Decolorization in UV/TiO2/O3, O3/Mn(II) and O3/MnO2 systems is suggested to proceed by mainly radical-, surface- and radical-type mechanisms, respectively. Additionally, direct ozonation cannot be ignored in O3/Mn(II) and O3/MnO2 systems.


Class III malocclusion: a cephalometric study of Saudi Arabians.
The records of 500 consecutive Saudi Arabian patients referred for orthodontic treatment were examined clinically and cephalometrically for Class III malocclusion. A control group was drawn at random from the same sample. The incidence of Class III was 9.4 per cent, with mandibular prognathism being the commonest presentation of the malocclusion. The upper and lower incisors exhibited a marked degree of dentoalveolar compensation, on dental bases having mean values of SNA--78.77 degrees and SNB--81.17 degrees. The maxillary length was reduced, as were the saddle and maxillary-mandibular plane angles. The gonial angle (ArGoMe), anterior and posterior facial heights, and mandibular lengths (ArGo, ArPo) were all significantly larger than the control group. The cephalometric values of the control group showed the increased tendency to bimaxillary protrusion in the Saudi Arabian sample.


Bacterial infection activates the immune system response and dysregulates microRNA expression in honey bees.
In insects, a rapid and massive synthesis of antimicrobial peptides (AMPs) is activated through signaling pathways (Toll and Imd) to combat invading microbial pathogens. However, it is still unclear whether different types of bacteria provoke specific responses. Immune response mechanisms and the activation of specific genes were investigated by challenging Apis mellifera workers with the Gram-negative bacterium Serratia marcescens or the Gram-positive bacterium Micrococcus luteus. The immune system responded by activating most genes of the Toll and Imd pathways, particularly AMP genes. However, genes specifically regulated by M. luteus or S. marcescens were not detected, suggesting an interaction between the signaling pathways that lead to immune effectors synthesis. Despite this finding, kappaB motifs in the 5'-UTRs of selected genes suggest a pathway-specific control of AMP and transferrin-1 gene expression. Regulation by miRNAs was also investigated and revealed a number of candidates for the post-transcriptional regulation of immune genes in bees.


Clinical Impact of Severe Obesity in Patients with Lymphoedema.
With the rate of obesity increasing worldwide, patients with lymphoedema with and without a concomitant diagnosis of severe obesity (SO) were compared in regard to their baseline demographics, health related characteristics, treatment plans, and patient outcomes. This was a retrospective observational cohort study. The IBM MarketScan database was examined (2013 - 2019) for patients with a new diagnosis of lymphoedema. Of 60 284 patients with lymphoedema identified, 6 588 had SO defined by a body mass index > 40 kg/m2. The demographics and other characteristics of SO were compared with patients with lymphoedema without SO. SO and lymphoedema diagnosis increased two fold from 2013 to 2019. The lymphoedema SO+ group was younger (57.8 vs. 60.8 years, p < .001) and with a higher proportion of men (37.7% vs. 24.9%, p < .001) than the lymphoedema SO- group. More comorbidities were observed in the lymphoedema SO+ group than the lymphoedema SO- group: diabetes 46.0% vs. 24.9 % (p < .001), heart failure 18.3% vs. 7.4% (p < .001), hypertension 75.0% vs. 47.6% (p < .001), and renal disease 24.8% vs. 11.9% (p < .001). Use of diuretics in the lymphoedema SO+ group was greater: 57.6% vs. 38.0% (p < .001). Patients with lymphoedema SO+ had higher risk of cellulitis: 34.5% vs. 13.5% (p < .001). Specific lymphoedema treatment was given more often to lymphoedema SO-: 66.3% vs. 64.3% (p = .003). This was significant for manual lymphatic drainage (46.6% vs. 40.0%; p < .001) and physical therapy (55.4% vs. 51.6%; p<.001), but not for compression garments (18.2% vs. 17.7%; p = .38). However, more patients with lymphoedema SO+ received pneumatic compression device treatment: 20.9% vs. 13.7% (p < .001). There was an increase in SO associated lymphoedema. Patients with lymphoedema SO+ have over a two and half fold increase in cellulitis incidence, with a significant increase in medical resource use and cost. Despite this, patients with lymphoedema and SO receive less specific therapy such as compression, which has proven to reduce cellulitis incidence.


Short- and long-term outcome and factors predicting survival after surgical tube cystostomy for treatment of obstructive urolithiasis in small ruminants.
To evaluate outcome of small ruminants after tube cystostomy without urethral flushing. Retrospective clinical study. Small ruminants (n=63; 50 goats, 13 sheep). Medical records (January 1996-October 2003) for all small ruminants undergoing tube cystostomy were analyzed. Signalment, laboratory data, intraoperative findings, urolith type, and postoperative outcome were compared. Long-term follow-up was obtained at 6 and > or= 12 months postoperatively. Most animals were castrated males. Pygmy goats were overrepresented. Mean time to normal urination after tube cystostomy was 11 days, and mean hospitalization was 14 days. Seventy-six percent of animals were successfully treated with tube cystostomy (90% of those discharged from hospital). Short- and long-term survival was good for those animals with follow-up data. Reobstruction occurred in <20% of animals at 6 and 12 months. Goats, castrated males, and animals with normal serum potassium, no fluid in the abdomen, or no urethral process amputation were more likely to survive. Stone type, bladder appearance, and age at castration were not associated with outcome. Surgical tube cystostomy without urethral flushing is an effective technique for resolution of obstructive urolithiasis in small ruminants. Goats, small ruminants with an intact urethral process, absence of abdominal fluid, and serum potassium concentration <5.2 mEq/L at admission were all associated with survival after tube cystostomy. Castrated males may also be more likely to survive. These factors should be considered in management of small ruminants with urolithiasis.


Change in volume magnetic susceptibility at the phase transition of dipalmitoylphosphatidylcholine.
We have observed a change at 41 degrees C in the relative volume magnetic susceptibility of an aqueous dispersion containing 13 wt% multilamellar dipalmitoylphosphatidylcholine (DPPC) vesicles. The magnitude of the change is consistent with the known density change of the phospholipid bilayer and the assumption that the mass susceptibility of the system is constant through the transition. The superconducting susceptometer used in this study of the sharp transition of DPPC will be able to detect 1% changes in bilayer density for 10 wt% dispersions even when the transition temperature and transition width of phospholipid vesicle under various experimental conditions.


The Swedish childhood diabetes study--social and perinatal determinants for diabetes in childhood.
Using the Swedish childhood diabetes register, a nationwide, case-referent study was performed from September 1, 1985 to August 31, 1986. Based on the information from a mailed questionnaire sent to all incident diabetic children and for each diabetic child - two referent children matched according to age, sex, and county, we have analysed perinatal events and aspects of the social environment as possible risk factors for Type 1 (insulin-dependent) diabetes in childhood. A significantly larger proportion of the mothers of the diabetic children were older than 40 years compared to those of the referent children (33% and 24%, p = 0.01 respectively). A smaller percentage of mothers of the diabetic children had a high educational level compared to mothers of referent children (10% and 15%, p = 0.03 respectively) and 39% of the fathers of the diabetic children were manual workers compared to 31% of the fathers of referent children (p = 0.03). Perinatal events did not differ between diabetic and referent children. In children 0-6 years, the duration of breast-feeding was significantly shorter in diabetic children than among referent children (median duration for diabetic children 5 months compared to 6 months for referent children p = 0.03). When considering the presence of Type 1 diabetes among relatives, maternal age over 40 years, low educational level of the mother, and the father being a manual worker as risk factors, the presence of 1 to 4 of any of these risk factors increased the relative risk for Type 1 diabetes cumulatively from 1.2-7.5.(ABSTRACT TRUNCATED AT 250 WORDS)


Transcriptomic analysis of the Myxococcus xanthus FruA regulon, and comparative developmental transcriptomic analysis of two fruiting body forming species, Myxococcus xanthus and Myxococcus stipitatus.
The Myxococcales are well known for their predatory and developmental social processes, and for the molecular complexity of regulation of these processes. Many species within this order have unusually large genomes compared to other bacteria, and their genomes have many genes that are unique to one specific sequenced species or strain. Here, we describe RNAseq based transcriptome analysis of the FruA regulon of Myxococcus xanthus and a comparative RNAseq analysis of two Myxococcus species, M. xanthus and Myxococcus stipitatus, as they respond to starvation and begin forming fruiting bodies. We show that both species have large numbers of genes that are developmentally regulated, with over half the genome showing statistically significant changes in expression during development in each species. We also included a non-fruiting mutant of M. xanthus that is missing the transcriptional regulator FruA to identify the direct and indirect FruA regulon and to identify transcriptional changes that are specific to fruiting and not just the starvation response. We then identified Interpro gene ontologies and COG annotations that are significantly up- or down-regulated during development in each species. Our analyses support previous data for M. xanthus showing developmental upregulation of signal transduction genes, and downregulation of genes related to cell-cycle, translation, metabolism, and in some cases, DNA replication. Gene expression in M. stipitatus follows similar trends. Although not all specific genes show similar regulation patterns in both species, many critical developmental genes in M. xanthus have conserved expression patterns in M. stipitatus, and some groups of otherwise unstudied orthologous genes share expression patterns. By identifying the FruA regulon and identifying genes that are similarly and uniquely regulated in two different species, this work provides a more complete picture of transcription during Myxococcus development. We also provide an R script to allow other scientists to mine our data for genes whose expression patterns match a user-selected gene of interest.


Erratum: ITPKA1 Promotes Growth, Migration and Invasion of Renal Cell Carcinoma via Activation of mTOR Signaling Pathway [Corrigendum].
[This corrects the article DOI: 10.2147/OTT.S266095.].


Intensity of care for cancer patients treated mainly at home during the month before their death: An observational study.
Little is known regarding healthcare for cancer patients treated mainly at home during the month before they die. The aim of this study was to provide information on how they were treated and what were their causes of death. This population-based observational study analysing information obtained from the French national healthcare data system (SNDS) included adult health insurance beneficiaries treated for cancer who died in 2015 after having spent at least 25 of their last 30 days at home. Among the cancer patients who died in 2015, 25,463 (20%) were included [mean age (±SD) 74±13.2 years, men 62%]; 54% of them died at home. They were slightly older (75 vs. 73 years) than those who died in hospital, had less frequently received hospital palliative care during the year preceding their deaths (19% vs. 41%) and had less often used medical transport (41% vs. 73%) to an emergency department (8% vs. 62%), to hospital-based (11% vs. 17%) or community-based (16% vs. 12%) chemotherapy, to a general practitioner (73% vs. 78%) or to a community-based nursing service (63% vs. 73%). However, when they consulted a general practitioner (median 3 visits vs. 2) or a nurse (median 22 nursing procedures vs. 10) during their last month of life, visits were more frequent. The leading cause of death was tumour, which represented 69% of deaths at home vs. 74% of deaths in hospital. In France, home management during the last month of life is uncommon and even when it is occurs, in one out of two cases patients pass away in a hospital setting. This study is an interrogation on medical choices, given the wish of many of the French to die at home and placing their choices in an international perspective.


Anatomical and technical considerations in surface electromyography.
Despite the technical and clinical limitations of surface EMG, it is essential in the physical medicine and rehabilitation field. Surface EMG has evolved from a secondary means of clinical assessment to a primary factor in determining and predicting clinical outcomes. Computer models of electrical muscular activity are currently implemented to assist in designing proper instrumentation and electrode with optimum dimensions. These models could be expanded to simulate pathological motor functions to help understand functional abnormalities even before clinical interventions. Currently, several groups all over the world are investigating the use of multichannel surface EMG. This technological advancement would have an immediate impact on several medical fields. For instance, tendon transfers are performed to improve function in peripheral nerve injury, brachial plexus lesion, spinal cord injury, and cerebral palsy. There are potential uses for multichannel surface EMG, both preoperatively and postoperatively. Preoperatively choosing the muscle for transfer has been largely based on clinical grounds. Multichannel surface EMG could give a more objective database to assess prognosis and determine which muscle to transfer. Postoperatively, multichannel surface EMG can provide a systematic way of assessing changes in gross muscle topography caused by the tendon transfer. Other applications of multichannel surface EMG would be for bony and soft tissue deformity from arthritis, heterotopic ossification, amputation, or burns. Multichannel surface EMG would allow clinicians to get a broader picture of the skeletal muscle activity despite the fact that it is physically impossible for the patient to assume the anatomic position used for traditional isolated electrode placement. Individuals with physical disabilities that affect their ability to assume the usual posture for electrophysiologic testing may benefit considerably from development of multichannel electrophysiologic testing. Patients with abnormalities of tone from various causes such as stroke, traumatic brain injury, and cerebral palsy are at times evaluated with kinesiologic EMG to assess motor control. Multichannel surface EMG could potentially give us much greater insight into motor control disorders.


Determination of neonicotinoid insecticides residues in eels using subcritical water extraction and ultra-performance liquid chromatography-tandem mass spectrometry.
A rapid, sensitive, and environmental-friendly multi-residue method has been developed for the simultaneous determination of seven neonicotinoid insecticides (dinotefuran, nitenpyram, thiamethoxam, imidacloprid, clothianidin, acetamiprid, and thiacloprid) residues in eel samples. Subcritical water extraction was investigated as a novel and alternative technology for the extraction of neonicotinoids from eel matrices and the results were compared with the conventional ultrasonic and shaking extraction. The target compounds were identified and quantitatively determined by ultra-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-MS/MS) operated in multiple reaction monitoring mode. Under the current optimized chromatographic conditions, each LC run was completed in 5 min. Average recoveries of the seven analytes from fortified samples ranged between 84.6% and 102.0%, with relative standard deviations (RSD) lower than 10.8%. The limits of detection (LODs) and quantification (LOQs) for neonicotinoids were in the ranges of 0.12-0.36 μg kg(-1) and 0.42-1.12 μg kg(-1), respectively. The proposed method is fast, sensitive, easy to perform, water-based thus more environmentally acceptable, making it applicable for high-throughput monitoring of insecticides residues in aquatic products.


Electronmicroscopic identification of type C particles in cultured murine neuroblastoma.
Monolayer of murine neuroblastoma were treated with dexamethasone and examined by electronmicroscopy. Most of the treated cells were morphologically differentiated and exhibited type C virus particles which were budding from the cell surface. This in vitro system may be of great value for exploring the oncogenic potential of the virus, and its possible role in cell differentiation.


Is road safety management linked to road safety performance?
This research aims to explore the relationship between road safety management and road safety performance at country level. For that purpose, an appropriate theoretical framework is selected, namely the 'SUNflower' pyramid, which describes road safety management systems in terms of a five-level hierarchy: (i) structure and culture, (ii) programmes and measures, (iii) 'intermediate' outcomes'--safety performance indicators (SPIs), (iv) final outcomes--fatalities and injuries, and (v) social costs. For each layer of the pyramid, a composite indicator is implemented, on the basis of data for 30 European countries. Especially as regards road safety management indicators, these are estimated on the basis of Categorical Principal Component Analysis upon the responses of a dedicated road safety management questionnaire, jointly created and dispatched by the ETSC/PIN group and the 'DaCoTA' research project. Then, quasi-Poisson models and Beta regression models are developed for linking road safety management indicators and other indicators (i.e. background characteristics, SPIs) with road safety performance. In this context, different indicators of road safety performance are explored: mortality and fatality rates, percentage reduction in fatalities over a given period, a composite indicator of road safety final outcomes, and a composite indicator of 'intermediate' outcomes (SPIs). The results of the analyses suggest that road safety management can be described on the basis of three composite indicators: "vision and strategy", "budget, evaluation and reporting", and "measurement of road user attitudes and behaviours". Moreover, no direct statistical relationship could be established between road safety management indicators and final outcomes. However, a statistical relationship was found between road safety management and 'intermediate' outcomes, which were in turn found to affect 'final' outcomes, confirming the SUNflower approach on the consecutive effect of each layer.


Current status and future perspectives of magnetic resonance high-field imaging: a summary.
There are several magnetic resonance (MR) imaging techniques that benefit from high-field MR imaging. This article describes a range of novel techniques that are currently being used clinically or will be used in the future for clinical purposes as they gain popularity. These techniques include functional MR imaging, diffusion tensor imaging, cortical thickness assessment, arterial spin labeling perfusion, white matter hyperintensity lesion assessment, and advanced MR angiography.


Revisiting Ebola Virus Disease infection control protocols at an academic level I trauma center: Successes, challenges, and ways ahead.
In the decade since the largest Ebola Virus Disease (EVD) outbreak in history, hospitals within the United States have discovered deficiencies in EVD infection control protocols. A large academic level I trauma medical center and frontline EVD receiving hospital in northeast Florida conducted a large-scale review and revision of the facility's EVD infection control protocols to increase preparedness. The revision process revealed opportunities for improvement and highlighted the need for excellent resource management and interdepartmental communication.


Do bubble characteristics affect recanalization in stroke patients treated with microbubble-enhanced sonothrombolysis?
Administration of microbubbles (MB) may augment the effect of ultrasound-enhanced systemic thrombolysis in acute stroke. Bubble structural characteristics may influence the effect of MB on sonothrombolysis. We aimed to compare the effects of galactose-based air-filled MB (Levovist) and sulphur hexafluoride-filled MB (Sonovue) on recanalization and clinical outcome. One hundred thirty-eight i.v. recombinant tissue plasminogen activator-(tPA-) treated patients with middle cerebral artery (MCA) occlusion were studied. Presence and location of arterial occlusion and recanalization (RE) were assessed using the thrombolysis in brain ischemia (TIBI) flow grading system. Patients underwent 2 h of continuous transcranial Doppler (TCD) monitoring and received three bolus of MB after 2, 20 and 40 min of tPA bolus. Ninety-one patients received Levovist (LV) and 47 received Sonovue (SV). NIHSS scores were obtained at baseline and after 24 h. Modified Rankin Scale (mRS) score was used to assess outcome at 3 mo. Median admission NIHSS was 17. On TCD, 96 (69.6%) patients had a proximal and 42 (30.4%) a distal MCA occlusion. Age, baseline NIHSS, clot location, stroke subtypes and time to treatment were similar between LV and SV groups. Recanalization rates after 1 h (32.2%/35.6%), 2 h (50.0%/46.7%) and 6 h (63.8%/54.5%) were similar in LV/SV groups (p > 0.3). Clinical improvement (NIHSS decrease >or= 4 points) at 24 h was similar in both groups (54.9%/51.1%, p = 0.400), as well as symptomatic intracranial haemorrhage rate (3.3%/2.1%, p = 0.580) and in-hospital mortality (8.1%/9.3%, p = 0.531). Similarly, the type of MB administered did not affect long-term outcome after sonothrombolysis. Forty-four percent of patients in the LV group and 48.5% in the SV group achieved functional independence (mRS <or= 2) at 3 mo (p = 0.440). MB administration during sonothrombolysis is associated with a high RE rate. However, RE rates, clinical course and long-term outcome are comparable when administering galactose-based air-filled MB (Levovist) or sulphur hexafluoride-filled MB (Sonovue).


Management of subglottic hemangiomas with carbon dioxide laser: Our 25-year experience and comparison with the literature.
Subglottic hemangiomas (SGH) are rare tumors of infancy arising between the perichondrium and the mucosa of the subglottic space. It is a potential life-threatening condition. Many therapeutic options exist for this disease, including lasers. To report our 25-year experience of laser treatment of SGH. Retrospective review of charts. Clarós' Otolaryngology and Head and Neck Surgery Clinic in Barcelona, Spain. We recruited a total of 97 patients of whom 89 were treated with CO2 laser. Mean age at first contact was 2.1 months (range: 1.5-6.5). Sex ratio was 10 girls for 1 boy. Eighty percent of patients presented with stridor and 30.3% with recurrent acute laryngitis. Forty percent had associated cutaneous hemangiomas. They received an average of 1.85 laser session (range: 1-4) and 78.5% were healed after a maximum of 2. We had a 100% success rate and 1.1% complication rate (subglottic stenosis). CO2 laser is a very effective and recommendable tool against subglottic hemangiomas. To achieve good results traditional laser safety measures should be respected besides some useful surgical tips.


Comparison of the effects of platelet-rich plasma and dexamethasone ınjection on scar formation after vocal fold ınjury in rabbits.
In this study, a histopathological comparison was aimed between platelet-rich plasma (PRP) injection and dexamethasone injection in the prevention of scar formation after vocal fold injury. Electrocautery was applied to damage the right and left vocal folds of a total of 12 New Zealand rabbits. PRP obtained from the rabbit's own blood was injected into the right vocal fold, and dexamethasone was injected into the left vocal fold. After 8 weeks, the experimental animals were euthanized, and the levels of inflammatory cell infiltration, vascularization, collagen, elastin, and hyaluronic acid (HA) were compared in histopathological evaluation. In statistical comparison of histopathological data obtained; in terms of plasma cell infiltration, vascularization, and edema parameters, statistically significant results were obtained in favor of the PRP group. Although the difference between collagen, elastin and HA, which are critical in vocal fold scar healing, was more positive in favor of PRP, no significant result was revealed in the statistical evaluation. PRP injection in rabbits with vocal fold damage reveals similar characteristics with dexamethasone injection in preventing scar formation. PRP injection has favorable effects on vascularization, prevention of edema, and number of plasma cells.


Nitrogen-15 partitioning within a three generation tiller sequence of the bunchgrass Schizachyrium scoparium: response to selective defoliation.
Nitrogen partitioning among three generations of tillers within the bunchgrass Schizachyrium scoparium var. frequens was investigated in a controlled environment as a potential mechanism of herbivory tolerance. Nitrogen-15 was transported from the labelled primary tiller generation to both shoots and roots of nondefoliated secondary and tertiary tiller generations within 24 h. Partial defoliation increased shoot nitrogen concentration of secondary and tertiary generation tillers by 110 and 120%, respectively, 24 h following defoliation. Shoot nitrogen concentration was preferentially increased by partial defoliation of tertiary generation tillers throughout the 120 h experimental period, but diminished to concentrations comparable to nondefoliated tillers within shoots of the secondary generation at 72 h. In contrast to nitrogen concentration, the total amount of nitrogen imported by secondary and tertiary generation tillers decreased 62 and 73%, respectively, 24 h following partial defoliation and did not attain values comparable to respective nondefoliated tillers. Consequently, preferential nitrogen concentration occurred in response to partial tiller defoliation without an increase in total nitrogen import based on the reduction in the total nitrogen requirement per tiller generation associated with defoliation. Estimates of both the total amount of nitrogen import and nitrogen concentration are necessary to accurately interpret the dynamics of intertiller nitrogen allocation.


[Polychlorinated biphenyls (PCB) in human adipose tissue].
This study describes the contamination of human adipose tissue with six selected polychlorinated biphenyls (PCB) known as "indicator congeners", with PCB no. 49 and the mixed inducer PCB nos. 156, 170, and 189. The low chlorinated biphenyls nos. 28, 49, and 52 could not be found in the tissue samples, while the average concentration of PCB no. 101 was 9.0 micrograms/kg. The content of PCB nos. 138, 153, and 180 was slightly below the values published by the "Deutsche Forschungsgemeinschaft" (DFG). The mixed inducer nos. 138, 156, 170, and 180 amounted to approximately 40% of all the PCBs measured. The PCB contamination was positively correlated with age: for the age group 61-70 years, with the exception of PCB no. 101, a distinct increase in the concentrations could be observed.


Loperamide potentiates doxorubicin sensitivity in triple-negative breast cancer cells by targeting MDR1 and JNK and suppressing mTOR and Bcl-2: In vitro and molecular docking study.
Multidrug resistance (MDR) is the leading cause of treatment failure in triple-negative breast cancer (TNBC) patients treated with doxorubicin (DXR). We aimed to investigate the potential of the antidiarrheal drug Loperamide (LPR) in sensitizing TNBC cells to DXR and elucidate the underlying molecular mechanisms. Therefore, we examined the effects of DXR alone or in combination with LPR on MDA-MD-231 cells viability using MTT assay, cell cycle, and apoptosis by flow cytometry, and the expression of the MDR-related genes (MDR1 and JNK1) and cell cycle/survival genes (p21, mTOR, and Bcl-2) by quantitative reverse transcription polymerase chain reaction. Results showed that adding LPR to DXR potentiated its antiproliferation effect and reduced its IC50 by twofolds compared with DXR alone. The value of the combination index of LPR/DXR was <1 indicating a synergistic effect. Combined DXR/LPR treatment also caused G1 arrest and potentiated apoptosis more than DXR-single treatment. At the molecular levels, LPR/DXR treatment downregulated the mRNA of MDR1 (1.35-folds), JNK1 (2.5-folds), mTOR (6.6-folds), Bcl-2 (9.5-folds); while upregulated p21 gene (8-folds) compared with DXR alone. Molecular docking analyses found LPR antagonizes MDR1 and JNK1 proteins, and hence supports the in vitro studies. In conclusion, the results confirmed the potential of LPR in sensitizing TNBCs to DXR by targeting MDR1 and JNK1 and suppressing Bcl-2 and mTOR genes, while upregulating the cell cycle inhibitor gene p21. Additionally, LPR could be repurposed to reduce the therapeutic doses of DXR as indicated by the dose reduction index (DRI) and subsequently decrease its side effects.


Magnetically Induced CO2 Methanation Using Exchange-Coupled Spinel Ferrites in Cuboctahedron-Shaped Nanocrystals.
Magnetically induced catalysis can be promoted taking advantage of optimal heating properties from the magnetic nanoparticles to be employed. However, when unprotected, these heating agents that are usually air-sensitive, get sintered under the harsh catalytic conditions. In this context, we present, to the best of our knowledge, the first example of air-stable magnetic nanoparticles that: 1) show excellent performance as heating agents in the CO2 methanation catalyzed by Ni/SiRAlOx, with CH4 yields above 95 %, and 2) do not sinter under reaction conditions. To attain both characteristics we demonstrate, first the exchange-coupled magnetic approach as an alternative and effective way to tune the magnetic response and heating efficiency, and second, the chemical stability of cuboctahedron-shaped core-shell hard CoFe2 O4 -soft Fe3 O4 nanoparticles.


Current status of 3D printing in spine surgery.
Three-dimensional printing (3DP) is one of the latest tools in the armamentarium of the modern spine surgeon. The yearning to be more precise and reliable whilst operating on the spine has led to an interest in this technology which has claimed to achieve these goals. 3D printing has been used pre-operatively for surgical planning and for resident or patient education. It has also found its way to the operation theatre where it is used to fabricate customized surgical tools or patient-specific implants. Several authors have highlighted significant benefits when 3D printing is used for specific indications in spine surgery. Novel applications of this technology in spine surgery have also been described and though still in a nascent stage, these are important for this technology to sustain itself in the future. However, major limitations have also come to light with this technology in use. This article seeks to review the current status and applications of 3D printing in spinal surgery and its major drawbacks while briefly describing the essentials of the technology. It is imperative that the modern spine surgeon knows about this important innovation and when and how it can be applied to improve surgical outcomes.


Near ultraviolet circular dichroism study of the cyclic AMP receptor protein, its NH2-terminal domain and their interaction with cyclic AMP.
Circular dichroism in the near ultraviolet wavelength range was employed to examine conformational features of CRP (a dimer with a chain of 209 amino acids) and of its subtilisin core -alpha CRP- which retains the cAMP binding site (a dimer spanning the sequence 1-117). Binding of the ligand cAMP (allosteric activator), as well as cGMP was also investigated. The well resolved transitions could be assigned to the various classes of aromatic amino acid residues in the two proteins. In addition to signals which are attributable to the missing aromatic residues (Phe-136 and Tyr-206) the difference spectrum (CRP minus alpha CRP) shows a significant perturbation of a tryptophanyl contribution centred at 296 nm. From the available X-ray structure of the cAMP-CRP complex we are led to conclude that a conformational reorganisation takes place in the alpha CRP. A very large negative maximum is observed at 255 nm when cAMP binds to CRP and to alpha CRP. The maximum effect is observed in both cases at a ratio of one ligand bound per protomer. In the 280-300 nm wavelength range a smaller but significant perturbation affects specifically the spectra and reveals different cAMP-induced conformational changes in the two proteins. We propose that the major (255 nm) contribution to the perturbation spectrum of bound cAMP, and the qualitatively similar signal for cGMP, reflects an immobilisation of the sugar and adenine moieties of the bound ligand in an almost anti-conformation for both CRP and alpha CRP.


Clozapine bioactivation induces dose-dependent, drug-specific toxicity of human bone marrow stromal cells: a potential in vitro system for the study of agranulocytosis.
Clozapine, an atypical antipsychotic drug effective in treatment of refractory schizophrenia causes potentially life-threatening agranulocytosis. The drug undergoes bioactivation to a toxic, chemically reactive intermediate with capacity to target stromal cells, central components of the bone marrow microenvironment implicated in neutrophil development. To identify possible mechanisms underpinning disruption of stroma as a site of drug bioactivation, toxicity was induced in vitro. Therefore metabolite generation procedures utilizing HOCl or HRP-H(2)O(2) as primary components involved in clozapine metabolism were adapted for stromal culture and coupled with viability determinations. Drug oxidation by HOCl was less toxic to stromal cells than HRP-H(2)O(2) based methods. More specifically, clozapine bioactivation by HRP-H(2)O(2) caused dose-dependent inhibition of stromal viability at therapeutically relevant concentrations. Differences in susceptibility of HAS303 and LP101 cells to the clozapine nitrenium ion were also evident. Stromal cell death was attributed to clozapine in the presence of a complete metabolising system comprising HRP and H(2)O(2). In the absence of a complete metabolising system clozapine was not cytotoxic. For LP101 cells, drug plus HRP (minus H(2)O(2)) also induced toxicity. Importantly, other antipsychotic drugs including risperidone, olanzapine and haloperidol when bioactivated, were not cytotoxic, indicating system specificity for clozapine. Exogenous GSH, N-acetylcysteine, l-ascorbic acid, catalase, and sodium azide afforded protection to cells whereas S-methylGSH, GSSG, ketoprofen and proadifen did not. Thus functional data derived from the in vitro stromal system defined in these studies may enable further investigation of the mechanisms subserving stromal impairment in clozapine-induced agranulocytosis and direct attention to improved methods for its prevention.


Lack of correlation between milk glucose concentrations and rates of milk production in the rat.
Concentrations of lactose, alpha-lactalbumin (alpha-la), glucose and glucose-6-phosphate were measured in milk obtained from rats under conditions where the rates of milk production varied from 0 to 2.6 g/h. In the milk from rats fed a low protein diet where milk production was 0.9 g/h, the concentration of alpha-la was 1.5 mg/ml, being significantly lower than that in the milk of control rats at 2.9 mg/ml and where the rate of milk production was 2.6 g/h. No differences were detected in the glucose concentrations. When rats were fed restricted amounts of the control diet and where milk production varied from 0 to 1.7 g/h during the course of the day, no differences in the concentrations of either alpha-la or glucose were detected. These results suggest that considerable caution must be used in interpreting the significance of milk glucose in the rat.


Using an Er,Cr:YSGG laser to remove lithium disilicate restorations: A pilot study.
The use of lasers is growing widely in dentistry. Despite its clinical implications, most information and clinical data related to the removal of ceramic restorations with the aid of a laser is either anecdotal or in the form of clinical reports. The purpose of this in vitro study was to establish a parameter on the removal of lithium disilicate crowns with a laser and conduct an in vitro trial of crown removal based on the wattage and time of application. Twenty extracted molars were prepared to accommodate a lithium disilicate disk specimen, which was cemented with resin cement. An erbium, chromium-doped yttrium, scandium, gallium, and garnet (Er,Cr:YSGG) laser was applied at different wattages (3, 3.5, 4, and 5 W) to determine the optimal wattage for the removal of the lithium disilicate specimens. Once the optimal wattage was established, 25 extracted teeth were mounted in stone, then prepared to receive milled lithium disilicate computer-aided design/computer-aided manufacturing complete coverage crowns. The crowns were cemented with a dual-polymerizing resin cement. The groups comprised 3.5 and 4 W output with 30-, 60-, and 90-second application time (n=5), and 5 crowns were removed using traditional handpiece and electric handpiece with coarse grit diamond rotary instruments. The results and time required to remove the crown were recorded. The chi-square test was performed to assess any significant differences in removing the crown with the laser according to wattage or time of application (α=.05). Laser application at 3.5 and 4 W was best for removing crowns conservatively. Eight crowns (40%) of 20 specimens were successfully removed at the first attempt. The majority of the crowns came off during the second attempt. The chi-square test revealed no significant difference between the combination of wattage and time of application (P= .92). The mean time to remove the lithium disilicate crown with a diamond rotary instrument was 6 minutes, and removal required 1.8 instruments on the average. An Er,Cr:YSGG laser can safely remove lithium disilicate crowns with the settings used this study.


Effects of ghrelin receptor agonist, relamorelin, on gastric motor functions and satiation in healthy volunteers.
Synthetic human ghrelin accelerates gastric emptying, reduces gastric accommodation, and results in numerical increases in postprandial symptom scores. The ghrelin receptor agonist, relamorelin, accelerates gastric emptying in patients with diabetic gastroparesis. To measure pharmacological effects of relamorelin on gastric accommodation, distal antral motility, and satiation in healthy volunteers. In a placebo-controlled, double-blind, randomized study of 16 healthy volunteers, we compared effects of 30 μg subcutaneous (s.c.) relamorelin to placebo on: (i) gastric volumes measured by single photon emission computed tomography, (ii) 1-h postprandial distal antral motility index (MI) by 15-lumen perfusion gastroduodenal manometry, and (iii) satiation tested by Ensure nutrient drink test. Primary endpoints were: fasting and postprandial gastric volumes, distal antral phasic pressure activity (number of contractions, mean amplitude, and MI), and maximum tolerated volume. Results were normally distributed and the two treatment groups were compared using t-test. Relamorelin, 30 μg s.c., significantly increased the number of contractions in the distal antrum during 0-60 min postmeal when compared to placebo (p = 0.022); this was also observed in the first two 15-min periods (p = 0.005 and 0.015 for number of contractions 0-15 and 16-30). There was borderline increase in MI0-15 (p = 0.055) and numerically increased MI0-60 (p = 0.139) and MI16-30 (p = 0.116). The amplitude of contractions was not significantly increased. Relamorelin did not significantly alter fasting or postprandial gastric volumes, gastric accommodation, or satiation volumes and symptoms. Relamorelin increases frequency of distal antral motility contractions without significant effects on amplitude of contractions. The lack of inhibition of accommodation and absence of increase in satiation symptoms support relamorelin for the treatment of symptomatic gastroparesis (ClinicalTrials.gov NCT02466711).


Comparison of topical nepafenac 0.1% with intravitreal dexamethasone implant for the treatment of Irvine-Gass syndrome.
To compare safety and efficacy of intravitreal dexamethasone (IVD) implant with topical nepafenac (TN) 0.1% in previously untreated Irvine-Gass syndrome (IGS) in clinical practice. This was a retrospective study of 62 eyes with IGS after phacoemulsification with posterior chamber intraocular lens (IOL) implantation. None of the patients used treatment before IVD or TN. Best-corrected visual acuity (BCVA) with Early Treatment Diabetic Retinopathy Study chart (ETDRS), slit-lamp, intraocular pressure (IOP) measurement, fundus examination, spectral-domain optical coherence tomography (OCT) and fundus florescein angiography were performed to all subjects at baseline, 1, 3 and 6mo. The mean BCVA of the IVD group was 49.3±6.8, and the mean BCVA of the TN group was 32.9±7.3 ETDRS letters in post-treatment month 6. The mean central macular thickness (CRT) of IVD group was 266.6±53.5 µm and the mean CRT of TN group was 364.9±56.3 µm in post-treatment month 6. Baseline BCVA has correlation with final BCVA in TN group however there was no correlation between baseline BCVA and final BCVA in IVD group. IVD is found to be better than TN in controlling pseudophakic macular edema and improving visual acuity. IVD group also has significantly lower CRT however IOP is not significantly different between two groups in post-treatment month 6.


The metabolism of n-nonane in male Fischer 344 rats.
The urinary metabolites of n-nonane in male Fischer 344 rats, after administering the hydrocarbon by gavage, included gamma-valerolactone, delta-hexanolactone, 2,5-hexanedione, delta-heptanolactone, 1-heptanol, 2-nonanol, 3-nonanol, 4-nonanol, 4-nonanone and 5-methyl-2-(3-oxobutyl)furan. Metabolism strongly favored the formation of monoalcohols and lactones, which are the products of appropriately substituted hydroxy carboxylic acids. The metabolites were identified using gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS). High pressure liquid chromatography (HPLC) permitted the detection of the dicarboxylic acids malonic acid and glutaric acid in the n-nonane dosed rat urines.


Recent advances in dual- and multi-responsive nanomedicines for precision cancer therapy.
Nanomedicines have been regarded as a potential approach in the field of cancer treatment due to their unique advantages. Although improved therapeutic efficacy can be achieved, the applications of most traditional nanomedicines are still limited by severe side effects resulting from unintended retention of therapeutic agents in non-diseased tissues. To increase the controllability of therapeutic agent accumulation in targeting sites (such as tumors), stimuli-responsive nanomedicines that realize drug release in response to exogenous or endogenous stimuli have been developed. In these stimuli-responsive nanomedicines, most of them are activated by mono type of stimulus, and therefore show unsatisfactory selectivity and specificity. In contrast, dual- and multi-responsive nanomedicines that integrate different responsive components into a signal nanoplatform can allow drug release in a more safe and effective manner, leading to both improved therapeutic efficacy and reduced systemic toxicity. Herein, we summarize recent advances in precision cancer therapy by using dual- and multi-responsive nanomedicines. The design strategies and working mechanisms of these dual- and multi-responsive nanomedicines and their applications in chemotherapy, phototherapy, and immunotherapy of cancer are introduced in detail. The existing challenges and future prospects are finally discussed in anticipation of accelerating the clinical translation of these nanomedicines.


Neonatal Outcome of Babies Born to Women 40 Years and over at the University Hospital of the West Indies 2012-2013.
This article aims to determine neonatal outcome of babies born to women ≥40 years at the University Hospital of the West Indies. This was a matched retrospective cohort study looking at the outcome of all babies born to women ≥40 years and control babies born to women aged 20-30 years at the University Hospital of the West Indies over a 2-year period. Maternal and neonatal demographic data and course of admission for admitted neonates were recorded. Descriptive analyses were performed. One hundred and ninety-eight neonates were born to women ≥40 years and 208 to their younger counterparts, M:F 1:1.2. There was no difference in the number of preterm or low birth weight infants, the number of neonates with a low 5 min Apgar score <7, the number of neonates admitted or the number of neonates who died between women ≥40 years and their younger counterparts (p > 0.05). No difference in adverse neonatal outcome was noted between women ≥40 years and their younger counterparts.


Nanoparticle-modified PMMA to prevent denture stomatitis: a systematic review.
This systematic review aimed to evaluate the antifungal effectiveness of polymethylmetacrylate (PMMA) modified by nanoparticles (NPs) and to compare it with conventional acrylic resins for denture bases. The present study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Searches were performed using PubMed, SCOPUS, SciELO, EMBASE, and LILACS. Eligibility criteria were as recommended by PRISMA. The studies presented great variability regarding NP type, synthesis method, antifungal evaluation method, and antifungal effect. The most commonly used NPs were silver (AgNP) and zinc oxide (ZnONP), ranging in size from 10 to 100 nm. The incorporation methods were mechanical or agitated. Despite PMMA modification by ZnONP being shown in vitro to be a combination with the best antifungal effect, future studies are still needed to determine the minimum inhibitory concentration for Candida spp. and assess its biocompatibility before the protocol is clinically tested.


Urolithin A protects human dermal fibroblasts from UVA-induced photoaging through NRF2 activation and mitophagy.
Photoaging, caused by exposure to sunlight and especially UVA, has been identified as one of the culprits for age-related skin deterioration. Here, we initially demonstrated that urolithin A (UroA), a metabolite derived from intestine microflora, possessed sufficient photoprotective capacity and attenuated UVA-induced senescent phenotypes in human fibroblasts, such as growth inhibition, senescence-associated β-galactosidase activity, breakdown of extracellular matrix, synthesis of senescence-associated secretory phenotypes and cell cycle arrest. Furthermore, UroA lessened the accumulation of intracellular reactive oxygen species, which promoted the phosphorylation and afterwards nuclear translocation of NRF2, subsequently driving the activation of downstream antioxidative enzymes. In parallel, we proved that UroA restored mitochondrial function by induction of mitophagy, which was regulated by the SIRT3-FOXO3-PINK1-PARKIN network. Taken together, our results showed that UroA protected dermal fibroblast from UVA damage through NRF2/ARE activation and mitophagy process, thus supporting UroA as a potential therapeutic agent for photoaging.


Food insecurity, mental health and quality of life among people living with HIV commencing antiretroviral treatment in Ethiopia: a cross-sectional study.
Studies from high-income settings show that both food insecurity and common mental disorders (CMDs) are associated with lower quality of life among people living with HIV (PLHIV). However, there is limited research among PLHIV in sub-Saharan Africa. In this study we tested the hypothesis that food insecurity and CMDs would be associated with poorer quality of life of PLHIV in Ethiopia. A cross-sectional study was carried out with 348 PLHIV who were initiating antiretroviral therapy recruited from two primary care centers and a tertiary Hospital in southwest Ethiopia. Food insecurity, CMD, and quality of life were measured using instruments adapted and validated in Ethiopia (Household Food Insecurity Access Scale, Kessler-6, and WHOQOL-HIV-BREF-ETH, respectively). Multiple linear regression analysis was used to identify factors associated with quality of life after adjusting for confounders. The prevalence of severe household food insecurity among PLHIV was 38.7 %. After adjusting for confounders, severe food insecurity (β = -3.24, 95 % CI: -6.19; -0.29) and higher levels of CMD symptoms (β = -1.72 for each 1 point increase, 95 % CI: -1.94; -1.49) were associated with lower quality of life. Other factors associated with lower quality of life were advanced HIV disease (β = -3.80, 95 % CI: -6.18; -1.42), and being underweight (BMI = 17.0 - 18.5 kg/m(2)) (β = -3.45, 95 % CI: -6.18; -0.71). Owning more household assets was associated with higher quality of life (β = 0.99 for owning one more asset, 95 % CI: 0.09; 1.89). Poor mental health and food insecurity are associated with lower quality of life in PLHIV. There is a need for longitudinal studies to elucidate the pathways linking CMD, food insecurity and quality of life.


[Toxicity study of epidermal growth factor eye medicine liquid].
To apply for a new medicine certificate, the experiments of acute, long toxicity and side effects of EGF eye medicine liquid were investigated in animals. All of examinations were done according to the instructions of "Requirements of the Toxicity Study of New Medicine" No toxicity or side-effect of EGF eye medicine liquid given by i.v., i.p., s.c. or eye-drop were been found. For the results of whole experiments are in complete accord with "the requirements of the toxicity study of new medicine", EGF eye medicine liquid will be safety in clinical application.


Cardiotoxicity of copper-based antineoplastic drugs casiopeinas is related to inhibition of energy metabolism.
Isolated rat hearts were perfused with glucose, octanoate or glucose + octanoate and different concentrations of the copper-based antineoplastic drugs casiopeina II-gly (CSII) or casiopeina III-i-a (CSIII). In isolated perfused hearts with glucose + octanoate, both casiopeinas induced diminution in cardiac work and O2 consumption with half-maximal inhibitory concentrations (IC50) of 4 (CSII) and 4.6 (CSIII) microM, after 1 h of perfusion. Strong inhibition of the pyruvate and 2-oxoglutarate dehydrogenases as well as total creatine kinase by casiopeinas suggested that ATP generation by oxidative phosphorylation and its transfer towards myofibrils were targets for these drugs. In consequence, the cellular contents of ATP and phosphocreatine were also lowered by casiopeinas. Remarkably, casiopeinas were less toxic than adriamycin (IC50 = 2.6 microM), a well-known potent cardiotoxic and antineoplastic drug, which has a wide clinical use. In an open-chest animal, which is a more physiological model than the isolated heart, femoral administration of 1 microM drug revealed that CSII was innocuous very likely due to strong binding to serum albumin, whereas adriamycin induced again a potent cardiotoxic effect (diminution in heart rate and severe depression of systolic blood pressure). Thus, it seems that casiopeinas are a group of new antineoplastic drugs with milder secondary toxic effects than proven drugs such as adriamycin.


Adjunctive treatment for acne vulgaris by tranexamic acid.
Acne is a chronic, inflammatory skin disorder of pilosebaceous units. Tranexamic acid (TXA) acts as a plasmin inhibitor to reduce blood loss and is also used to treat rosacea due to its anti-inflammatory effects. Some parts of the pathogenesis of rosacea are similar to inflammatory acne. The study aimed to evaluate the efficacy of 10% TXA serum in treating acne and its adverse effects. A randomized, double-blind, placebo-controlled, split-face study was performed on 18 mild-to-moderate acne patients. Patients applied 10% TXA serum on one side of the face and placebo on another side twice daily for 8 weeks. Acne lesion counts and adverse effects were evaluated every 2 weeks. Significant differences in total inflammatory acne counts were observed between TXA and placebo since Week 4 (p = 0.008). TXA mainly reduced papules and pustules, as papule counts significantly decreased since the 8th week (p = 0.046) and pustule counts significantly reduced since Week 8 (p = 0.033). Moreover, physicians also found that TXA serum reduced the redness of the skin, corresponding with the imaging from VISIA® Skin Analysis. The anti-inflammatory effect of TXA resulted in less PIE and PIH. Adverse effects, including erythema and scaling, were treated by applying any moisturizing cream. Topical 10% TXA can reduce inflammatory acne effectively. Adverse effects were minor and treat easily.


Interception and retention of Chernobyl-derived 134Cs, 137Cs and 106Ru in a spruce stand.
The time dependence of the specific activity of Chernobyl-derived 134Cs, 137Cs and 106Ru was determined in vegetation and soil samples from an old spruce stand within a period of 600 days after the beginning of the radioactive fallout. The results show that 70% of the total activity of radiocesium and 60% of radioruthenium deposited in the spruce stand were retained initially in the canopy. They were removed from the needles and twigs as a result of weathering (rain, wind, litter fall) and transferred to the forest floor, but only rather slowly (half-lives in the canopy: radiocesium, 90 days for the period 0-130 days, 230 days for the period 130-600 days; radioruthenium, 95 days for the period 0-200 days). The transfer of radiocesium and ruthenium to the forest floor by litter-fall was small when compared with that of weathering by rain or wind (radiocesium 7%, radioruthenium 8%, with respect to the total activity deposited in the canopy). The total deposition of radiocesium and ruthenium in the spruce stand was higher by 20 and 24%, respectively, than that observed in nearby grassland. The deposition velocity of radiocesium in the spruce stand was estimated at 5.5 mm s-1, higher by a factor of 10 than the figure for grassland. Similar values were found for radioruthenium.


'Everything is okay': the influence of neoliberal discourse on the reported experiences of Aboriginal people in Western Australia who are HIV-positive.
While Australian Aboriginal conceptions of health have been described as holistic and collective, contemporary approaches to health services and health research are often premised on the rational, reflexive subject of neoliberal discourse. This paper considers how neoliberal conceptions of health and subjectivity arose and were negotiated in the context of a qualitative research project on Aboriginal experiences of HIV in Western Australia. Questions about 'coping', 'future' and 'life changes' stood out in the interview transcripts as examples of neoliberal discourse. This paper explores the reflexive, contextual and deflective responses to these questions and suggests they demonstrate how neoliberal discourse can produce the impression that 'everything is okay' despite the difficult social and economic conditions of everyday life experienced by many Aboriginal people. Aboriginal people with a chronic and serious infectious disease such as HIV may utilise the language of self-management and responsibility when talking about HIV with a non-Aboriginal researcher for pragmatic and utilitarian reasons. In this way, the responses of the Aboriginal participants in this study provide a valuable opportunity for exploring new approaches to both research methodology and health service delivery.


Infection-related atlantoaxial subluxation (Grisel syndrome) in an adult with Down syndrome.
Case report. To report an adult case with Down syndrome, in whom infection-related atlantoaxial subluxation (Grisel syndrome) developed. Atlantoaxial instability is a common complication in Down syndrome patients; however, there have been limited reports of adult-onset atlantoaxial subluxation with myelopathy. Grisel syndrome has been characterized as a nontraumatic atlantoaxial subluxation associated with pharyngeal infection. It usually affects children, and the subluxation can be successfully reduced by conservative treatments in most cases. A 26-year-old man with Down syndrome suffered from retropharyngeal infection, after which his atlantoaxial subluxation was aggravated and myelopathy developed. He was treated with administration of antibiotics and application of a halo-vest. The conservative treatments failed to reduce the atlantoaxial subluxation. We performed a C1 laminectomy and posterior occipitocervical fusion, which successfully relieved his symptoms. CONCLUSION.: This experience suggests that when Down syndrome patients have retropharyngeal infection, we should consider the possible aggravation of atlantoaxial instability and development of myelopathy, even if the patient is an adult.


Safety instrumented functions and safety integrity levels (SIL).
This paper discusses two performance-based standards, ANSI/ISA S84.01 and IEC d61508, and the requirements they place upon user companies of electrical, electronic and programmable electronic safety related systems (E/E/PE SRS) or Safety Instrumented Systems (SIS). To comply to the requirements of the standards, a user company would have to: (a) identify the safety target level of the process; (b) evaluate the hazardous events that pose a risk higher than the safety target level; (c) determine the safety function(s) that must be implemented in an SIS to achieve the safety target level; (d) implement the safety functions in an SIS and evaluate its safety integrity level (SIL); (e) install, test and commission the SIS; and (f) verify that the installed SIS does in fact reduce the process risk to below the safety target level. Several risk analysis techniques that can be used to comply with the aforementioned requirements are discussed and a simple example is used to illustrate the use, advantages and disadvantages of the techniques. The evaluation of SIL of the SIS (probability to fail to respond to a process demand) is outside the scope of this paper.


Expression, purification, and spectroscopic characterization of human thromboxane synthase.
Thromboxane A2 (TXA2) is a potent inducer of vasoconstriction and platelet aggregation. Large scale expression of TXA2 synthase (TXAS) is very useful for studies of the reaction mechanism, structural/functional relationships, and drug interactions. We report here a heterologous system for overexpression of human TXAS. The TXAS cDNA was modified by replacing the sequence encoding the first 28 amino acid residues with a CYP17 amino-terminal sequence and by adding a polyhistidine tag sequence prior to the stop codon; the cDNA was inserted into the pCW vector and co-expressed with chaperonins groES and groEL in Escherichia coli. The resulting recombinant protein was purified to electrophoretic homogeneity by affinity, ion exchange, and hydrophobic chromatography. UV-visible absorbance (UV-Vis), magnetic circular dichroism (MCD), and electron paramagnetic resonance (EPR) spectra indicate that TXAS has a typical low spin cytochrome P450 heme with an oxygen-based distal ligand. The UV-Vis and EPR spectra of recombinant TXAS were essentially identical to those of TXAS isolated from human platelets, except that a more homogenous EPR spectrum was observed for the recombinant TXAS. The recombinant protein had a heme:protein molar ratio of 0.7:1 and a specific activity of 12 micromol of TXA2/min/mg of protein at 23 degreesC. Furthermore, it catalyzed formation of TXA2, 12-hydroxy-5,8,10-heptadecatrienoic acid, and malondialdehyde in a molar ratio of 0.94:1.0:0.93. Spectral binding titrations showed that bulky heme ligands such as clotrimazole bound strongly to TXAS (Kd approximately 0.5 microM), indicating ample space at the distal face of the heme iron. Analysis of MCD and EPR spectra showed that TXAS was a typical low spin hemoprotein with a proximal thiolate ligand and had a very hydrophobic distal ligand binding domain.


The foamy virus envelope glycoproteins.
The main functions of retroviral glycoproteins are recognition and binding to the cellular virus receptor as well as fusion of viral and cellular lipid membranes to release the viral particle into the cytoplasm of the host cell. Foamy viruses (FVs) are a special group of retroviruses with a very broad host range that use a currently unknown cellular receptor for entry. Nevertheless, many functions of the FV envelope glycoproteins in the viral replication cycle have been characterized in detail over the last years. Several unique features not found for any other retrovirus were identified. These include the presence of two types of FV Env proteins, gp170(Env-Bet) and gp130Env, and the strict requirement of gp130Env coexpression for the FV budding and particle release process, a function that cannot be compensated for by any other viral glycoprotein tested so far. Furthermore, domains in gp130Env could be characterized that influence its intracellular distribution, cell surface transport, and its specific interaction with the viral capsid during particle egress. In addition, it has recently been shown that gp130Env expression alone induces release of subviral particles from cells. This review summarizes the current knowledge about the nature of the FV Env proteins and their function in the viral replication cycle.


Determination of normal regional left ventricular function from cine-MR images using a semi-automated edge detection method.
A semi-automated edge detection method for the delineation of the endo- and epicardial borders of the left ventricle from cine MR images has been developed. The feasibility of this was demonstrated by processing end diastolic and end systolic ECG-gated images of four short axis images in 10 healthy subjects. The first derivative method combined with a 2D weighted polynomial fitting procedure was used to determine the endo- and epicardial borders, which then allowed determination of the wall motion, wall thickening, and ejection fraction, of the left ventricle. The results show that the end-systolic radial wall motion varies from (32+/-8)% to (76+/-12)%, and wall thickening from (0.60+/-0.46) cm to (1.26+/-0.50) cm. An average ejection fraction of (69+/-6)% was found which agrees well with literature values. The method described, for the delineation of the borders, reduces considerably the long and tedious operator time inherent in manual measurement and greatly increases the reproducibility of the measurements.


Implications of bidirectional flow in the great arteries at the 11-14-week scan.
To determine the implications of a bidirectional Doppler flow pattern detected in one or both of the fetal great arteries in the first trimester. Database records were reviewed for cases of bidirectional flow found on fetal echocardiography performed at less than 15 weeks of gestation between January 1999 and October 2006 inclusive. Bidirectional flow consisted of antegrade flow in systole and retrograde flow in diastole. Data including indication for fetal echocardiography, gestational age at diagnosis, the anatomical features, karyotype, nuchal translucency measurement and outcome were collected. From almost 2500 scans, bidirectional flow was detected in a total of 15 fetuses. The abnormal flow pattern was confined to the aorta in four, to the pulmonary artery in four, and was present in both great arteries in a further seven fetuses. Eight of the 15 fetuses had regurgitation at one or both atrioventricular valves. Additional cardiac abnormalities were detected by ultrasound in eight cases. Of the 13 cases for which the karyotype was known, 12 were abnormal and five of these had trisomy 18. None of the fetuses survived. There were two intrauterine deaths and 13 terminations of pregnancy. Bidirectional flow in one or both great arteries is an unusual finding at the first-trimester scan and must be distinguished from the retrograde flow occurring only in systole in duct-dependent heart defects. It carries a poor prognosis, which is a consequence of both the high chance of underlying chromosomal abnormality and the hemodynamic compromise associated with severe arterial valve regurgitation.


Long non-coding RNA ESCCAL-1/miR-590/LRP6 signaling pathway participates in the progression of esophageal squamous cell carcinoma.
Long non-coding RNAs (lncRNAs) have critical functions within esophageal squamous cell carcinoma (ESCC). However, the function and mechanism underlying ESCC-associated lncRNA-1 (ESCCAL-1) in ESCC tumorigenesis have not been well clarified. ESCCAL-1, miR-590 and LRP6 were quantified using qRT-PCR. Cell viability, migration and invasion abilities were measured using CCK-8 assay and transwell assays. The protein pression was determined with western blot assay. The xenograft model assays were used to examine the impact of ESCCAL-1 on tumorigenic effect in vivo. Direct relationships among ESCCAL-1, miR-590 and LRP6 were confirmed using dual-luciferase reporter assays. The present work discovered the ESCCAL-1 up-regulation within ESCC. Furthermore, ESCCAL-1 was found to interact with miR-590 and consequently restrict its expression. Functionally, knocking down ESCCAL-1 or over-expressing miR-590 hindered ESCC cell growth, invasion, and migration in vitro. Moreover, inhibition of miR-590 could reverse the effect of knockdown of ESCCAL-1 on cells. Importantly, it was confirmed that LRP6 was miR-590's downstream target and LRP6 over-expression also partly abolished the role of miR-590 overexpression in ESCC cells. We have uncovered a novel regulatory network comprising aberrant interaction of ESCCAL-1/miR-590/LRP6 participated in ESCC progression.


Antiplasmodial, anti-complement and anti-inflammatory in vitro effects of Biophytum umbraculum Welw. traditionally used against cerebral malaria in Mali.
Biophytum umbraculum Welw. (Oxalidaceae) is a highly valued African medicinal plant used for treatment of cerebral malaria, a critical complication of falciparum malaria. To provide additional information about traditional use of B. umbraculum and to test plant extracts and isolated compounds for in vitro activities related to cerebral malaria. The traditional practitioners were questioned about indication, mode of processing/application, dosage and local name of B. umbraculum. Organic extracts and some main constituents of the plant were investigated for anti-malaria, anti-complement activity and inhibition of NO secretion in a RAW 264.7 cell line. Treatment of cerebral malaria was the main use of B. umbraculum (fidelity level 56%). The ethyl acetate extract showed anti-complement activity (ICH50 5.7±1.6μg/ml), inhibition of macrophage activation (IC50 16.4±1.3μg/ml) and in vitro antiplasmodial activity (IC50 K1 5.6±0.13μg/ml, IC50 NF54 6.7±0.03μg/ml). The main constituents (flavone C-glycosides) did not contribute to the activity of the extract. Inhibition of complement activation and anti-inflammatory activity of B. umbraculum observed in this study might be possible targets for adjunctive therapy in cerebral malaria together with its antiplasmodial activity. However, clinical trials are necessary to evaluate the activity due to the complex pathogenesis of cerebral malaria.


Holmium laser enucleation of the prostate in Jehovah's Witness patients.
To evaluate if HoLEP is a viable option for male patients with medication-refractory urinary symptoms due to an enlarged prostate who are surgical candidates, but do not accept blood product transfusion. Between August 2008 and March 2019, nine Jehovah's Witness patients were undergoing HoLEP for relief of lower urinary tract symptoms and urinary retention. We described change in hemoglobin, change in PSA, enucleated prostate weight, enucleation and morcellation times, length of stay, and postoperative retention rate. The average age was 71.4 years (range 53-87). Urinary retention requiring catheterization was present in seven patients (78%). Two patients had a known diagnosis of prostate cancer preoperatively. The mean preoperative PSA on average was 21.6 ng/dL. Patients had a wide range of gland sizes, with a mean enucleated weight of 141 g (range 18-344 g). Mean reduction in hemoglobin was 16.9% following HoLEP. All patients managed to void postoperatively. All but one patient went home on postoperative day 1, and this patient went home on postoperative day 2. No patients required blood product transfusion or return to the operating room for clot irrigation postoperatively. HoLEP is a reasonable option for Jehovah's Witness and other patients with contraindications to blood product transfusion requiring surgical management of urinary symptoms due to enlarged prostate.


Acrylamide binding to the DNA and protamine of spermiogenic stages in the mouse and its relationship to genetic damage.
Mice received an intraperitoneal injection of 14C-labeled acrylamide (AA) at an exposure of 125 mg/kg to equal that used in genetic studies carried out by Shelby et al. (1986). Subsequently, spermatozoa were recovered from the reproductive tracts of the animals over a 3-week period and assayed for the amount of bound AA. A strong increase in the level of binding occurred in late-spermatid to early-spermatozoa stages; these same stages are also genetically most sensitive to the action of AA. At all time points, alkylation of DNA within the sperm accounted for a very small fraction (generally less than 0.5%) of the total sperm-head alkylation. However, alkylation of protamine, a protein unique to sperm cells, was found to be correlated with total sperm-head alkylation and accounted for essentially all of the AA binding. Two radioactive adducts were found in hydrolysed protamine samples, one of which co-eluted with a standard of S-carboxyethylcysteine. Protamine alkylation appears to be a significant cause of acrylamide-induced genetic damage in spermiogenic cells of the mouse.


Development of lead (Pb) tolerant strain by protoplast technology and their remediation.
The lead is poisonous metal and because of its chemical nature it acts as an environmental contaminant through the water or soil and it becomes toxic to humans. The toxicity of Pb occurs as a change in the conformation of nucleic acid and protein, inhibition of enzyme activity, disruption of membrane function and oxidative phosphorylation. For protoplast preparation, the removal of the cell wall and protoplast formation obtained by specific lytic enzyme. In cytoplasmic membrane, the envelope of bacteria consists of overlying cell wall. From hypertonic environment, the complete cell wall removal occurs due to which it maintains the osmotic integrity of the cell and produces the protoplast. In current work, protoplasts were produced by specific lytic enzyme (lysozyme and macerozyme), chemo fused (with the help of Polyethylene Glycol) and regenerated from strains Staphylococcus sp. and Bacillus sp. The fused protoplast was spherical in shape observed under microscopy. Colonies were screened on specific medium supplemented with Pb (Concentration at the rate of 1.5mM). One resistant colony (MICBT-1) was selected and further examined and applied for the transformation of Pb in the broth medium. The strain removed 98% of Pb at 1mM concentration. Next, sucrose containing medium was best which gives maximum protoplast regeneration. From various organisms, fusion technique has been used to combine the genes to create the strains having desired properties. This is a significant technique for engineering of bacterial strains for advantageous applied properties. Further MICBT-1 applied in artificially contaminated soil and removed maximally in exchangeable fraction (remains up to 0.05 mM). An efficient bioremediating agent for lead transformation from soil and water is expected to ease the ever-increasing problem. Further, it is needful to obtain new strain with the help of protoplast technology which can reduce the pollutant. This lead tolerant strain can be applied for bioremediation purposes in the Pb contaminated soil and water environment.


Transcatheter closure of atrial septal defect in a geriatric population.
To evaluate the efficacy and safety of transcatheter closure of atrial septal defects (ASD) in patients over 70 years of age. Transcatheter closure of ASD is an established procedure in children and young adults, but the benefits of this procedure in geriatric patients are still unclear. Between 2005 and 2010, 430 patients with ASD underwent transcatheter closure in our hospital. Among those patients, 30 consecutive patients older than 70 years of age were prospectively evaluated. Mean age at procedure was 75.8 ± 3.8 years (range: 70-85 years). Mean Qp/Qs was 2.4 ± 0.7 and mean ASD diameter was 20.3 ± 6.4 mm. Nine patients (30%) had a history of hospitalization due to heart failure. ASD closure was successfully performed in 28 patients (93%) without significant complications. During the follow-up period (mean period of 19.1 ± 11.3 months), New York Heart Association (NYHA) functional class was significantly improved in 20 patients (74%). Significant improvements of plasma BNP level, resting heart rate, and systolic pulmonary artery pressure were also observed. Improvement of tricuspid regurgitation was observed in 11 of 17 patients with moderate or severe regurgitation during the follow-up period. Conversely, worsening of mitral regurgitation was observed in 10 of the 27 patients. Transcatheter closure of ASD in geriatric patients can be performed safely. This procedure contributes to significant improvement of symptoms and positive cardiac remodeling. Long-term follow-up is mandatory, especially for patients with mitral regurgitation.


Identification of 4-[1-[3-chloro-4-[N'-(5-fluoro-2-methylphenyl)ureido]phenylacetyl]-(4S)-fluoro-(2S)-pyrrolidinylmethoxy]benzoic acid as a potent, orally active VLA-4 antagonist.
Optimization of benzoic acid derivatives by introducing substituents into the diphenyl urea moiety led to the identification of compound 20l as a potent VLA-4 antagonist. Compound 20l inhibited eosinophil infiltration into bronchial alveolar lavage fluid in a murine asthma model by oral dosing and its efficacy was comparable to anti-mouse alpha4 antibody (R1-2). Furthermore, this compound significantly blocked bronchial hyper-responsiveness in the model.


Positivity of extrapulmonary Ga-67 uptake in sarcoidosis: thyroid uptake due to chronic thyroiditis and bone uptake due to fibrous dysplasia.
Ga-67 citrate scintigraphy was performed on a 29-year-old man who had been diagnosed as having pulmonary sarcoidosis by a transbronchial lung biopsy. A Ga-67 citrate scintigram showed increased uptake not only in the pulmonary hilum and mediastinum, but also in the thyroid gland and the right ilium. Chronic thyroiditis was confirmed by aspiration biopsy of the thyroid gland, and fibrous dysplasia was confirmed by CT guided biopsy of the right ilium. Extrapulmonary Ga-67 uptake in patients with sarcoidosis does not necessarily indicate the involvement of other tissues and organs.


A rare presentation of central pontine myelinolysis secondary to hyperglycaemia.
Central pontine myelinolysis (CPM) is a rare demyelinating disorder caused by the loss of myelin in the center of the basis pontis. CPM typically occurs with rapid correction of severe chronic hyponatremia and subsequent disturbances in serum osmolality. Although hyperglycaemia is recognized as a pathogenetic factor in serum osmolality fluctuations, CPM is rarely seen in the context of diabetes. A 66-year-old Chinese male presented with a history of gait imbalance, mild slurred speech and dysphagia for two weeks. MRI showed the mass lesions in the brainstem, and laboratory examinations showed high blood glucose and HbA1c, as well as increased serum osmolality. The patient was diagnosed with CPM secondary to hyperosmolar hyperglyceamia and received insulin treatment as well as supportive therapy. After six weeks of followup, the patient had fully recovered to a normal state. CPM is a potentially fatal neurological condition and can occur in uncontrolled diabetes mellitus. Early diagnosis and timely treatment are crucial for improving the prognosis.


Key factors associated with the under-prescription of statins in elderly coronary heart disease patients: Results from the ELIAGE and ELICOEUR surveys.
The reasons why statins are under-utilized in elderly patients remain poorly understood. The aim of this study was to identify the reasons given by cardiologist for the non-prescription of statins in elderly CHD patients. Two cross-sectional pharmaco-epidemiological surveys were carried out among French cardiologists. The sample consisted of 1148 coronary patients aged 35 to 69 years and 1489 patients aged > or =70 years. Patients' risk factors, medical history, treatments, lipid values and the physicians' various motives for the non-prescription of statins were recorded. Patients not treated with statins reached 37% in the age-group > or =70 years and 14% in the age-group 35-69 years. The main reason given for statin non-prescription was the lack of a medical indication (2.5% of the age-group 35-69 years and 14% of the age-group > or =70 years). Among patients > or =70 years, the lack of indication was more often cited in the following conditions: 1) in very old patients (36% of lack of indication in the age-group >85 years vs. 10% in 70-75 years), 2) when lipid values were not available (20% when data were not available vs. 9%) and 3) when the patient had no prior history of myocardial infarction (MI) (20% when no history of MI vs. 7%). These factors were not associated with lack of indication among patients <70 years. History of intolerance or side effect was given for 1.3% and 14% of patients for each of the groups (35-69 and > or =70) and poor overall patient adherence was cited in 1% and 2%, respectively. The primary reason for the under-prescription of statins in elderly coronary patients is the perceived lack of indication, which stresses the need of extensive guidelines for prescription in elderly patients. Several factors associated with this perception seem to be specific to the elderly.


Management of an Isolated Left Vertebral Artery on the Arch During Zone 2 Landing Thoracic Endovascular Aortic Repair: A Multicentre Retrospective Study.
To compare the early and midterm outcomes of three different strategies for an isolated left vertebral artery on the arch (LVoA) revascularisation during thoracic endovascular aortic repair (TEVAR) with a proximal zone 2 landing. Between January 2016 and December 2021, 67 patients with LVoA and aortic arch pathologies who underwent zone 2 landing TEVAR at four medical centres were enrolled. These patients were divided into three groups for comparison: the novel chimney (group A, n = 28) with the right brachial-left brachial through and through (RLT) procedure; in vitro fenestration (group B, n = 24); and transposition (group C, n = 15). The flow direction and velocity of the LVoA was examined by Doppler ultrasound in the pre-, intra-, and post-operative periods. Primary outcomes were all cause mortality and new neurological symptoms. No deaths or new neurological symptoms occurred within 30 days. Early type Ia endoleak rates were 18% (n = 5), 17% (n = 4), and 0% in groups A, B, and C, respectively (p = .22). All patients had antegrade flow of the LVoA. The mean ± standard deviation duration of follow up was 63.6 ± 4.0 months. No deaths were observed during follow up. The rates of new neurological symptoms were 0%, 8%, and 33% in groups A, B, and C, respectively. The rates of midterm type Ia endoleak were 7%, 12%, and 0% in groups A, B, and C, respectively (p = .35). Bidirectional flow rates in the LVoA were 0%, 21%, and 27% in groups A, B, and C, respectively (p = .021). Two (8%) and three (20%) patients in groups B and C underwent a secondary procedure because of mild dizziness, but this was not necessary in group A (p = .058). The novel chimney technique of the RLT procedure may be feasible for patients with a LVoA requiring zone 2 anchoring. Accurate determination of the safety and feasibility of this novel technique requires larger sample sizes and longer follow up.


Ultrasonic-assisted extraction, analysis and properties of mung bean peel polysaccharide.
In order to improve the yield of mung bean peel polysaccharide, on the basis of single-factor experiments, the ultrasonic assisted extraction conditions were optimized by response surface methodology (RSM). The results showed that under the conditions of material-liquid ratio of 1: 40, temperature 77 °C, ultrasonic power 216 W and extraction time 47 min, the extraction rate of mung bean peel polysaccharide was the best, which was 2.55 %. The extracted polysaccharide was phosphorylated and its antioxidant activity in vitro was studied. The results suggested that the modified polysaccharide had a significant scavenging effect on hydroxyl radicals and enhanced the ability of anti-lipid peroxidation, which offered ideas and methods for the development and application of mung bean peel polysaccharide.


Folding of single-stranded DNA on the histone octamer.
A complex between the single-stranded DNA of the bacteriophage M13 and the histone octamer was analyzed by electron microscopy, low-angle X-ray diffraction and nuclease analysis. The morphology and the diffraction pattern of the complex strongly resemble those of the nucleosome. These results, as well as the finding of a protected DNA fragment about 100 nucleotides long following single-stranded DNA specific nuclease digestion, indicate that 'a nucleosome-like' complex can be formed between single-stranded DNA and the histone octamer. Competition experiments suggest that under physiological conditions the histone octamer is transferred from single- to double-stranded DNA.


Nucleotide-metabolizing enzymes and lymphocyte differentiation.
Inherited deficiencies of adenosine deaminase and purine nucleoside phosphorylase have been found to be associated with certain immunodeficiency syndromes which are characterized by deficiencies of mature peripheral lymphocytes. The immunodeficiency states associated with these enzyme deficiencies are thought to arise from blocks in lymphocyte differentiation. Deficiencies of these enzymes have profound and apparently selective effects on lymphocyte differentiation. Their discovery has focused attention on previously unknown relationships between purine nucleotide metabolism and lymphocyte development and function. In this article three aspects of nucleotide-metabolizing enzymes and lymphocyte differentiation will be discussed: 1) the distribution of the enzymes among lymphocyte populations at differing stages of differentiation; 2) the possible biochemical mechanisms which give rise to the immunodeficiencies; 3) the stages of lymphocyte differentiation which are affected by the enzyme deficiencies.


Synovial chondromatosis of the temporomandibular joint with intracranial extension.
An unusual case of synovial chondromatosis of the temporomandibular joint with intracranial extension, which resulted in complete dehiscence of the floor of the middle cranial fossa, is reported. An overview of the current literature and a discussion of the diagnosis and surgical management of synovial chondromatosis are presented.


Non-marine Ostracoda (Crustacea) of the Early Cretaceous Pre-Salt sediments of Brazil: An illustrated catalogue of the type specimens of Wicher, Krmmelbein, Krmmelbein amp; Weber, and Bate.
Type material of 10 genera, one subgenus, 110 species and 28 subspecies described by Wicher (1959), Krmmelbein (1961, 1962, 1963, 1964a,b, 1965a,b), Krmmelbein Weber (1971) and Bate (1972, 1994) are re-illustrated using optical digital technology in order to provide a standard reference for future systematic work and its biostratigraphical and palaeoenvironmental application. The genera are: Brasacypris, Coriacina, Hourcqia, Ilhasina, Looneyellopsis, Pattersoncypris, Petrobrasia, Reconcavona, Salvadoriella, and Tucanocypris, and subgenus Cypridea (Sebastianites).