[Development of researches on acupuncture stimulation-induced regulatory effect under pathological state based on resting-state functional magnetic resonance technology].
Using keywords of "acupuncture, fMRI and resting state", authors of the present paper retrieved papers in both Chinese and English from CNKI and PubMed databases without time limitation. A total of 13 articles (11 for acupuncture and 2 for moxibustion) met the standards were subjected to analysis. Of the 13 papers, 6 involve acupuncture analgesia, 2 moxibustion analgesia, 3 mild cognitive impairment, one involves stroke, and the rest one is for depression. Research results of acupuncture analgesia revealed that the analgesic effect is closely related to its regulation on "pain matrix" brain regions and pain-related default mode network. In the studies, a single acupoint is often used, without acupoints-combined recipes. Therefore, it is highly recommended that researchers pay more attention to (OD studies on the underlying mechanism of moxibustion, and (improvement of design protocols targeting requirements of acupuncture clinical practice.


Assisted death and martyrdom.
Against the backdrop of ancient, mediaeval and modern Catholic teaching prohibiting killing (the rule against killing), the question of assisted suicide and euthanasia is examined. In the past the Church has modified its initial repugnance for killing by developing specific guidelines for permitting killing under strict conditions. This took place with respect to capital punishment and a just war, for example. One wonders why in the least objectionable instance, when a person is already dying, suffering, and repeatedly requesting assistance in dying, there is still such widespread condemnation of assisted suicide and euthanasia. In a Gedankexperiment, I suggest that certain stories of martyrdom in the history of the Christian Church shed some light on the role of taking one's life, or putting one's life in danger out of love. I further suggest that requesting assisted suicide and/or euthanasia from the motive of love of one's family or care givers might possibly qualify as one instance of justifiable euthanasia, although I acknowledge that the Church will not be making changes in its stance any time soon.


[Mechanism of strategic management of a sanatorium-and-spa facility under current economic conditions].
The existing system of management of sanatorium-and-spa facilities constitutes a major economic risk factor under current socio-economic situation. One of the most important conditions for the sustainable continuation of activities of a sanatorium-and-spa institution is its adaptability to the changing economic environment. Those health care providers are likely to have an advantage in new conditions that offer a larger scope of specialized services, simultaneously reduces their costs and prices, introduce resource-saving technologies, and stimulate motivation of the medical personnel.


Topologically Protected Metallic States Induced by a One-Dimensional Extended Defect in the Bulk of a 2D Topological Insulator.
We report ab initio calculations showing that a one-dimensional extended defect generates topologically protected metallic states immersed in the bulk of two-dimensional topological insulators. We find that a narrow extended defect, composed of periodic units consisting of one octagonal and two pentagonal rings (a 558 extended defect), embedded in the hexagonal bulk of a bismuth bilayer, introduces two pairs of one-dimensional counterpropagating helical-Fermion electronic bands with the opposite spin-momentum locking characteristic of the topological metallic states that appear at the edges in two-dimensional topological insulators. Each one of these pairs of helical-Fermion bands is localized, respectively, along each one of the zigzag chains of bismuth atoms at the core of the 558 extended defect, and their hybridization leads to the opening of very small gaps (6 meV or less) in the helical-Fermion dispersions of these defect-related modes. We discuss the connection between the defect-induced metallic modes and the helical-Fermion edge states that occur on bismuth bilayer ribbons.


Flow Heterogeneity and Factors Contributing to the Variability in Retinal Capillary Blood Flow.
Capillary flow plays an important role in the nourishment and maintenance of healthy neural tissue and can be observed directly and non-invasively in the living human retina. Despite their importance, patterns of normal capillary flow are not well understood due to limitations in spatial and temporal resolution of imaging data. Capillary flow characteristics were studied in the retina of three healthy young individuals using a high-resolution adaptive optics ophthalmoscope. Imaging with frame rates of 200 to 300 frames per second was sufficient to capture details of the single-file flow of red blood cells in capillaries over the course of about 3 seconds. Erythrocyte velocities were measured from 72 neighboring vessels of the parafoveal capillary network for each subject. We observed strong variability among vessels within a given subject, and even within a given imaged field, across a range of capillary flow parameters including maximum and minimum velocities, pulsatility, abruptness of the systolic peak, and phase of the cardiac cycle. The observed variability was not well explained by "local" factors such as the vessel diameter, tortuosity, length, linear cell density, or hematocrit of the vessel. Within a vessel, a moderate relation between the velocities and hematocrit was noted, suggesting a redistribution of plasma between cells with changes in flow. These observations advance our fundamental understanding of normal capillary physiology and raise questions regarding the potential role of network-level effects in explaining the observed flow heterogeneity.


Effects of 10 days administration of percutaneous dihydrotestosterone on the pituitary-testicular axis in normal men.
Dihydrotestosterone (DHT) was administered percutaneously in a dose of 125 mg twice daily for 10 days to 12 normal men. Basal plasma levels of testosterone (T), 17 beta-estradiol (E2), and LH were measured every 2 days in these men and every 5 days in subjects from a control group receiving placebo. The daytime course of plasma hormone levels between two DHT applications was studied in six men. LRH tests were performed in nine men before and on day 10 of DHT administration. Plasma levels of free T and free E2, and T - E-binding globulin capacity and affinity were measured in six men before and on days 5 and 10 of DHT administration. Before DHT administration, there was no difference in basal plasma levels of T, DHT, E2, and LH between the control and the DHT-treated group. In the latter group, plasma DHT levels increased sharply from 0.52 +/- (+/- SE) to 3.70 +/- 0.92 ng/ml on day 2 (P less than 0.001) during DHT treatment. Plasma T, E2, and LH levels decreased significantly from 7.33 +/- 0.74 to 1.33 +/- 0.54 ng/ml (P less than 0.001), from 46 +/- 5 to 20 +/- 3 pg/ml (P less than 0.01), and from 7.8 +/- 1 to 4.2 mIU/ml (P less than 0.05), respectively. Except for a small decrease in plasma DHT (P less than 0.05) 12 h after the previous DHT application, hormone levels were stable during the time between the two DHT treatments. The responses of LH and FSH to LRH were not different before and on day 10 of DHT administration. Plasma levels of free T and free E2 as well as those of total T and E2 decreased; however, the percentages of unbound T and E2 were not different before and during DHT administration. T - E-binding globulin capacity and affinity were not modified by DHT administration. Changes in plasma DHT levels were negatively correlated with those in The results of this study demonstrate that 10-days DHT administration has an inhibitory effect on the hypothalamo-pituitary-testicular axis in normal men.


Coevolution of parasite virulence and host mating strategies.
Parasites are thought to play an important role in sexual selection and the evolution of mating strategies, which in turn are likely to be critical to the transmission and therefore the evolution of parasites. Despite this clear interdependence we have little understanding of parasite-mediated sexual selection in the context of reciprocal parasite evolution. Here we develop a general coevolutionary model between host mate preference and the virulence of a sexually transmitted parasite. We show when the characteristics of both the host and parasite lead to coevolutionarily stable strategies or runaway selection, and when coevolutionary cycling between high and low levels of host mate choosiness and virulence is possible. A prominent argument against parasites being involved in sexual selection is that they should evolve to become less virulent when transmission depends on host mating success. The present study, however, demonstrates that coevolution can maintain stable host mate choosiness and parasite virulence or indeed coevolutionary cycling of both traits. We predict that choosiness should vary inversely with parasite virulence and that both relatively long and short life spans select against choosy behavior in the host. The model also reveals that hosts can evolve different behavioral responses from the same initial conditions, which highlights difficulties in using comparative analysis to detect parasite-mediated sexual selection. Taken as a whole, our results emphasize the importance of viewing parasite-mediated sexual selection in the context of coevolution.


Synovial cysts of the spine: long-term follow-up after surgical treatment of 141 cases in a single-center series and comprehensive literature review of 2900 degenerative spinal cysts.
OBJECTIVE Synovial cysts of the spine are rare lesions, predominantly arising in the lumbar region. Despite their generally benign behavior, they can cause severe symptoms due to compression of neural structures in the spinal canal. Treatment strategies are still a matter of discussion. The authors performed a single-center survey and literature search focusing on long-term results after minimally invasive surgery. METHODS A total of 141 consecutive patients treated for synovial cysts of the lumbar spine between 1997 and 2014 in the authors' department were analyzed. Medical reports with regard to signs and symptoms, operative findings, complications, and short-term outcome were reviewed. Assessment of long-term outcome was performed with a standardized telephone questionnaire based on the Oswestry Disability Index (ODI). Furthermore, patients were questioned about persisting pain, symptoms, and further operative procedures, if any. Subjective satisfaction was classified as excellent, good, fair, or poor based on the Macnab classification. RESULTS The approach most often used for synovial cyst treatment was partial hemilaminectomy in 70%; hemilaminectomy was necessary in 27%. At short-term follow-up, the presence of severe and moderate leg pain had decreased from 93% to 5%. The presence of low-back pain decreased from 90% to 5%. Rates of motor and sensory deficits were reduced from 40% to 14% and from 45% to 6%, respectively. The follow-up rate was 58%, and the mean follow-up period was 9.3 years. Both leg pain and low-back pain were still absent in 78%. Outcome based on the Macnab classification was excellent in 80%, good in 14%, fair in 1%, and poor in 5%. According to the ODI, 78% of patients had no or only minimal disability, 16% had moderate disability, and 6% had severe disability at the time of follow-up. In this cohort, 7% needed surgery due to cyst recurrence, and 9% required a delayed stabilization procedure after the initial operation. CONCLUSIONS Surgical treatment with resection of the cyst provides favorable results in outcome. Excellent or good outcome persisting for a long-term follow-up period can be achieved in the vast majority of cases. Complication rates are low despite an increased risk of dural injury. With facet-sparing techniques, the stability of the segment can be preserved, and resection of spinal synovial cysts does not necessarily require segmental fusion.


A digital health application for managing pediatric asthma: Use and benefits.
Childhood asthma is a common and serious chronic lung disease. Mobile health (mHealth) technologies may assist clinical providers, caregivers, and children in managing pediatric asthma. This study evaluated the Nemours app, an mHealth application. We examined: a) frequency of data access by providers and feature use by caregivers (parents/legal guardians) of 5-11-year-old children diagnosed with asthma and b) whether utilization was related to benefits. Nine providers (allergists/pulmonologists) and 80 patient-families (caregiver/child dyads) participated. Two-years of retrospective data were obtained for asthma control, in-person urgent healthcare utilization, and app utilization. Six-months of prospective data included asthma control, in-person urgent healthcare utilization, app utilization, surveys, and health literacy screeners. Providers (56%) accessed app data and caregivers (61%) utilized the app. Caregiver use of messaging feature predicted gains in health literacy scores (b = .44, p = .041), suggesting app use may offer some educational benefits. Implementation of strategies that support app engagement and utilization may help to maximize intended benefits.


The effect of educating the use of spray by visual concept mapping method on the quality of life of children with asthma.
One of the most important goals in treating chronic diseases, especially asthma, is the promotion of quality of life (QOL). The present study aimed at identifying the effect of educating method on the QOL of children, who suffered from asthma.In this clinical trial study, 80 children aged 6-12 years with asthma were divided into two groups: control (face-to-face method) and experimental (visual concept mapping method). The QOL of both groups was measured before and after educating by the Juniper's Quality of Life Questionnaire with a one-month interval.The rate of change in the QOL score of the experimental group was 0.3 (±0.7) both before and after intervention and 0.1 (±0.3) in the control group, which was statistically significant (p<0.05).Educating by the visual concept mapping method with regard to the manner of using sprays is taken into account as an efficient and effective method in improving the QOL of children with asthma.


Isolation and characterization of bioactive polyacetylenes Panax ginseng Meyer roots.
Panax ginseng has been studied for its chemo-preventive properties and pharmaceutical potential. Polyacetylenic compounds isolated from Panax ginseng root typically comprised of non-polar C17 compound have been reported to exhibit bioactive properties. The objective of this project is to extract, isolate, and characterize bioactive polyacetylenes from Panax ginseng root using various extraction and separation methods Ginseng was extracted by reflux using methanol, ethanol, hexane, ethyl acetate, methanolic ultrasonication. The extracts were partitioned with hexane to obtain water-soluble portion and hexane-soluble portion. Hexane was subsequently removed under vacuum, and formed a crude polyacetylenes extract (crude PA). Silica gel chromatography and semi-preparative HPLC were utilized to prepare 5 fractions and the polyacetylenes were measure by HPLC and molecular weights confirm my APCI-MS and MNR. The bioactive effect was measured by MTT viability assay using murine 3T3-L1 cells. Extraction with methanol under reflux produced significantly larger amount of polyacetylenes (p<0.05). Liquid-liquid extraction and column chromatography were used to separate polyacetylenic compounds into five different fractions. Major polyacetylenes, panaxynol and panaxydol were found in fraction 1 and 2 respectively. Dose-response relationships were observed in 3T3-L1 cells and LC50 were 13.52±3.05μg/mL (fraction 1), 3.69±1.09μg/mL (fraction 2), 52.88±11.16μg/mL (fraction 3), 85.91±27.37μg/mL (fraction 4) and 135.52±32.91μg/mL (fraction 5). Fraction 2 containing panaxydol was found to have exhibited the greatest anti-proliferative effects on 3T3-L1 preadipocytes. Extraction with methanol under reflux produced significantly more polyacetylenes. Fractions that contain panaxydol was the most cytotoxic.


Chronic inflammation and pain in a tumor necrosis factor receptor (TNFR) (p55/p75-/-) dual deficient murine model.
Many aspects of tissue damage after acute or chronic inflammatory reactions can be attributed directly to the concomitant biosynthesis and release of inducible early proinflammatory cytokine tumor necrosis factor alpha (TNFα). Conversely, systemic inflammation is impacted by the consequences of tissue damage. Dysregulated TNFα contributes to numerous pathophysiologic conditions including inflammatory bowel disease (IBD) and arthritis. Inflammatory stimuli trigger proteolytic cleavage and shedding of extracellular domains of TNFα receptors giving rise to 2 soluble fragments (p55 soluble tumor necrosis factor receptor 1 (sTNFR1) and p75 sTNFR2) that block the additional binding, activity, and synthesis of TNFα. We hypothesized that absence of sTNFR inhibitory feedback control would result in accumulated high levels of TNFα and other inflammatory factors promoting the cardinal signs of chronic inflammation and pain. The current study reports a translational murine model of chronic arthritis precipitated by 2 consecutive inflammatory insults. The "double hit" procedures provoke a chronic inflammatory response and pain-related behaviors in mice that are dually deficient in p55 (TNFR1) and p75 (TNFR2). The inflammation- and pain-related behaviors are transient in similarly treated wild-type (WT) mice. The complete Freund's adjuvant (CFA) method was used initially to induce knee joint inflammation, tactile mechanical and heat hypersensitivity, and gait disturbance. After these transient effects of the insult were resolved, a recrudescence persisting at least through 23 weeks was promoted by gastrointestinal (GI) insult with dilute intracolonic mustard oil (MO) only in the mutant mice and was reversed by a P2X7 antagonist. A serum proteome profiling analysis revealed high levels of serum inflammatory factors TNFα, regulated upon activation normally T-cell expressed and secreted (RANTES), chemokine (C-X-C motif) ligand 9 [CXCL9 (MIG)], chemokine (C-X-C motif) ligand 10 [CXCL10 (IP-10)], and chemokine (C-C motif) ligand 2 [CCL2 (MCP-1)]. These data suggest that impaired signaling of TNFα as a result of the deficit of the 2 protective soluble p55 and p75 sTNFR inhibitory factors plays a pivotal role in the reactivation of the immune response to GI insult that can produce recrudescence of inflammatory injury and a chronic pain state through promotion of high levels of serum inflammatory factors.


On target.
AMANDA MARKALL is bringing 30 years of NHS experience, much of it working as a nurse, to her new role ensuring that more patients receive their care more swiftly. She is the new interim planned-care specialist at the Heart of England NHS Foundation Trust, Birmingham, where she has been brought in to help the trust reach its cancer and 18-week referral-to-treatment-time targets. The trust has missed the latter target since January this year and has also been failing to achieve the 62-day and two-week waiting-time targets concerning cancer.


Using data mining technology to explore homocysteine at low levels.
A high homocysteine level is known to be an independent risk factor for cardiovascular diseases; however, whether or not low homocysteine level contributes to any damage to the body has not been extensively studied. Furthermore, acquiring healthy subject databases from domestic studies on homocysteine is not trivial. Therefore, we aimed to investigate the causality between serum homocysteine levels and health status and lifestyle factors, particularly with a focus on low serum homocysteine levels. Additionally, we discussed a systematic methodical platform for data collection and statistical analysis, using the descriptive analysis of the chi-square test, t test, multivariate analysis of variance, and logistic regression.This study was a cross-sectional analysis of 5864 subjects (i.e., clients of a health examination clinic) in Taipei, Taiwan during a general health check-up in 2017. The patients' personal information and associated links were excluded. A sample group was selected as per the health criteria defined for this research whose data were processed using SPSS for descriptive statistical analysis using chi-square test, t test, multivariate analysis of variance, and logistic regression analysis.Those working for >12 hours/day had a higher homocysteine level than those working for <12 hours/day (P < .001). The average serum homocysteine level was 7.9 and 8.6 mol/L for people with poor sleep quality and good sleep quality, respectively (P = .003). The homocysteine value of people known to have cancer was analyzed using the logistic regression analysis, revealing a Δodds value of 0.898. The percentage of subjects with a homocysteine value of ≤6.3 μmol/L, who perceived their health status as "not very good" or "very bad," was higher than those with a higher homocysteine level. The number of subjects who perceived their health as poor was higher than expected.The results suggest that the homocysteine level could be an effective health management indicator. We conclude that normal homocysteine level should not be ≤6.3 μmol/L. Moreover, homocysteine should not be considered as harmful and its fluctuations from the normal range could be utilized to infer a person's physical status for health management.


Matrix stiffness affects endocytic uptake of MK2-inhibitor peptides.
In this study, the role of substrate stiffness on the endocytic uptake of a cell-penetrating peptide was investigated. The cell-penetrating peptide, an inhibitor of mitogen-activated protein kinase activated protein kinase II (MK2), enters a primary mesothelial cell line predominantly through caveolae. Using tissue culture polystyrene and polyacrylamide gels of varying stiffness for cell culture, and flow cytometry quantification and enzyme-linked immunoassays (ELISA) for uptake assays, we showed that the amount of uptake of the peptide is increased on soft substrates. Further, peptide uptake per cell increased at lower cell density. The improved uptake seen on soft substrates in vitro better correlates with in vivo functional studies where 10-100 µM concentrations of the MK2 inhibitor cell penetrating peptide demonstrated functional activity in several disease models. Additional characterization showed actin polymerization did not affect uptake, while microtubule polymerization had a profound effect on uptake. This work demonstrates that cell culture substrate stiffness can play a role in endocytic uptake, and may be an important consideration to improve correlations between in vitro and in vivo drug efficacy.


Role of imaging methods in diagnosis and treatment of Morton's neuroma.
Among the many causes of forefoot pain, Morton's neuroma (MN) is often suspected, particularly in women, due to its high incidence. However, there remain controversies about its relationship with symptomatology and which diagnostic and treatment choices to choose. This article mainly focuses on the role of the various imaging methods and their abilities to support an accurate diagnosis of MN, ruling out other causes of forefoot pain, and as a way of providing targeted imaging-guided therapy for patients with MN.


CoaDTI: multi-modal co-attention based framework for drug-target interaction annotation.
The identification of drug-target interactions (DTIs) plays a vital role for in silico drug discovery, in which the drug is the chemical molecule, and the target is the protein residues in the binding pocket. Manual DTI annotation approaches remain reliable; however, it is notoriously laborious and time-consuming to test each drug-target pair exhaustively. Recently, the rapid growth of labelled DTI data has catalysed interests in high-throughput DTI prediction. Unfortunately, those methods highly rely on the manual features denoted by human, leading to errors. Here, we developed an end-to-end deep learning framework called CoaDTI to significantly improve the efficiency and interpretability of drug target annotation. CoaDTI incorporates the Co-attention mechanism to model the interaction information from the drug modality and protein modality. In particular, CoaDTI incorporates transformer to learn the protein representations from raw amino acid sequences, and GraphSage to extract the molecule graph features from SMILES. Furthermore, we proposed to employ the transfer learning strategy to encode protein features by pre-trained transformer to address the issue of scarce labelled data. The experimental results demonstrate that CoaDTI achieves competitive performance on three public datasets compared with state-of-the-art models. In addition, the transfer learning strategy further boosts the performance to an unprecedented level. The extended study reveals that CoaDTI can identify novel DTIs such as reactions between candidate drugs and severe acute respiratory syndrome coronavirus 2-associated proteins. The visualization of co-attention scores can illustrate the interpretability of our model for mechanistic insights. Source code are publicly available at https://github.com/Layne-Huang/CoaDTI.


Patient and procedural factors associated with an increased risk of harm or death in the first 4,000 incidents reported to webAIRS.
This report describes an analysis of patient and procedural factors associated with a higher proportion of harm or death versus no harm in the first 4,000 incidents reported to webAIRS. The report is supplementary to a previous cross-sectional report on the first 4,000 incidents reported to webAIRS. The aim of this analysis was to identify potential patient or procedural factors that are more common in incidents resulting in harm or death than in incidents with more benign outcomes. There was a >50% higher proportion of harm (versus no harm) for incidents in which the patient's body mass index (BMI) was <18.5 kg/m2, for incidents in post-anaesthesia care units and non-theatre procedural areas, and for incidents under the main category of cardiovascular or neurological. The proportion of incidents associated with death was also higher (risk ratio >1.5) for BMI <18.5 kg/m2, incidents in non-theatre procedural areas, and incidents under the main category of cardiovascular or neurological. In addition, the proportion of incidents associated with death was higher for incidents in which the patient's age was >80 years, the American Society of Anesthesiologists physical status was 4 or 5, incidents involving non-elective procedures, and incidents occurring after hours (1800 to 0800 hours). When faced with incidents with these potential risk factors, anaesthetists should consider earlier interventions and request assistance at an earlier stage. Educational strategies on incident prevention and management should place even further emphasis on scenarios involving these factors.


Temporal stability of bacterial symbionts in a temperate ascidian.
In temperate seas, both bacterioplankton communities and invertebrate lifecycles follow a seasonal pattern. To investigate whether the bacterial community associated with the Mediterranean ascidian Didemnum fulgens exhibited similar variations, we monitored its bacterial community structure monthly for over a year using terminal restriction fragment length polymorphism and clone library analyses based on a nearly full length fragment of the 16S rRNA gene. D. fulgens harbored a bacterial consortium typical of ascidians, including numerous members of the phylum Proteobacteria, and a few members of the phyla Cyanobacteria and Acidobacteria. The overall bacterial community in D. fulgens had a distinct signature from the surrounding seawater and was stable over time and across seasonal fluctuations in temperature. Bacterial symbionts were also observed around animal cells in the tunic of adult individuals and in the inner tunic of D. fulgens larvae by transmission electron microscopy. Our results suggest that, as seen for sponges and corals, some species of ascidians host stable and unique bacterial communities that are at least partially inherited by their progeny by vertical transmission.


Suicidal ideation and associated factors among adolescents in northeastern Brazil.
This study aimed to identify the prevalence and factors associated with suicidal ideation among Brazilian adolescents. The instrument designed for the research was used considering three models with outcomes that identified the following: (a) adolescent had considered suicide, (b) adolescents have planned suicide, and (c) adolescents have attempted suicide. Logistic Regression was used in all models with significance level of 5%. An association between being female and suicidal ideation (OR = 2.18, CI 95% 1.60 to 2.97), suicide planning (OR = 1.80, CI 95% = 1.26-2.56), and suicide attempt (OR = 2.91, CI 95% 1.79 to 4.75) was found. Violent behavior/involvement in fights was associated with thinking about suicide (OR = 2.00, CI 95% = 1.43 to 2.81), suicide planning (OR = 1.65, CI 95% = 1.10-2.46), and suicide attempt (OR = 2.35, CI 95% = 1.49 to 3.70). For cigarette consumption, association was found with suicide ideation (OR = 1.62, CI 95% 1.03 to 2.55), planning (OR = 1.88, CI 95% = 1.15 to 3.08), and attempt (OR = 2.35, CI 95% 1.37 to 4.03). For alcohol consumption, association was found with suicide ideation (OR = 1.93, CI 95% 1.47 to 2.54), planning (OR = 2.22, CI 95% 1.61 to 3.08), and attempt (OR = 1.73, CI 95% 1.15 to 2.59). It was concluded that suicidal ideation was associated with female sex, involvement in fights, and illicit drug use.


Preliminary studies on acute and subacute toxicity of an antidiabetic herbal preparation, Dianex.
Dianex, a polyherbal formulation intended to use for diabetic patients, has been screened for toxic effects. For acute toxicity studies, Dianex was administered orally in graded doses of 0.75-10 g/kg to the mice. For subacute toxicity studies, different doses of Dianex (1.0, 1.5 and 2.5 g/kg) were administered orally to the rats once daily for 30 days. Animals were observed for physiological and behavioural responses, mortality, food and water intake and body weight changes. Hematological evaluation was performed weekly. All the animals were sacrificed on 31st day and changes in organ weights and histology were examined. Biochemical studies were done in liver and serum. No mortality was observed up to 10 g/kg of Dianex in acute toxicity study. Daily administration of as high as 2.5 g/kg dose of Dianex did not result in any mortality or changes in gross behaviour, body weight, weight and histology of different organs or serum and liver biochemistry. However, significant increase in RBC count and hemoglobin level was observed in the treated animals at all doses. Other peripheral blood constituents were in the normal range. The dose of Dianex to produce significant antidiabetic activity in mouse, 0.25-0.5 g/kg, is much lower than the doses used in the present study. Therefore such doses may be safe for daily administration without causing any serious side effects.


Migraine is associated with altered levels of neurotrophins.
Neurotrophic factors have been implicated in hyperalgesia and peripheral levels of these molecules were altered in behavioral and neurological disorders. The objectives of this study were to assess neurotrophic factors levels in migraine patients in comparison with controls, and to investigate whether there was any association between them and clinical parameters. This was a cross-sectional study. We measured serum levels of neurotrophin family members - nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 and 4/5 (NT3 and NT4/5) - and glial cell line-derived factor (GDNF) in patients suffering from migraine and matched controls. One hundred forty-one people were enrolled in this study, seventy-one were migraine patients and seventy were controls. Migraine patients showed more depressive and anxiety symptoms than control individuals as assessed, respectively, by the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory. Chronic and episodic migraine patients showed higher NT4/5 levels than control individuals (P=0.001). Patients with chronic migraine had lower levels of BDNF that were not influenced by the presence of depressive symptoms (P=0.02). This is the first report to evaluate NT3 and NT-4/5 levels in migraine patients. Our findings suggest a possible role of neurotrophic factors in migraine pathophysiology.


Population study of the risk of fetal death and its relationship to birthweight, gestational age, and race.
With more than 20,000 fetal deaths occurring annually in the United States, accurate epidemiological data concerning fetal death offer the potential to develop interventions aimed at saving a considerable number of fetuses. Currently, fetal death rates are determined by dividing the number of deaths by total births. These raw death rates do not focus on cause or preventability, nor do they delineate the risk for a individual pregnancy or any specific gestational age. Using data from 747,033 births in Illinois from 1984 to 1988, we estimated the fetal death risk (FDR) according to fetal weight and gestational age expressed as a function of the number of remaining fetuses. This procedure permits the comparison of FDR across all weights (including fetuses with growth retardation and macrosomia) and gestational ages. In addition, we examined the effect of race on this analysis. Between 28 and 36 weeks' gestational age, white fetuses with mean weights have a constant risk of fetal death at 0.1/1000 remaining fetuses. The risk is two to three times greater for black fetuses. If the fetus has growth retardation or is appropriately grown beyond 37 weeks' gestational age, the FDR increases further, with black fetuses remaining at higher risk. These data attempt to quantify the risk of fetal death. They support the widely held belief that the risk of fetal death increases in the presence of intrauterine growth retardation, but they also demonstrate that the risk of fetal death for all fetuses, including those appropriately grown, increases exponentially after 37 weeks' gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)


Protein arginine N-methyltransferase 4 (PRMT4) contributes to lymphopenia in experimental sepsis.
One hallmark of sepsis is the reduced number of lymphocytes, termed lymphopenia, that occurs from decreased lymphocyte proliferation or increased cell death contributing to immune suppression. Histone modification enzymes regulate immunity by their epigenetic and non-epigenetic functions; however, the role of these enzymes in lymphopenia remains elusive. We used molecular biological approaches to investigate the high expression and function of a chromatin modulator protein arginine N-methyltransferase 4 (PRMT4)/coactivator-associated arginine methyltransferase 1 in human samples from septic patients and cellular and animal septic models. We identified that PRMT4 is elevated systemically in septic patients and experimental sepsis. Gram-negative bacteria and their derived endotoxin lipopolysaccharide (LPS) increased PRMT4 in B and T lymphocytes and THP-1 monocytes. Single-cell RNA sequencing results indicate an increase of PRMT4 gene expression in activated T lymphocytes. Augmented PRMT4 is crucial for inducing lymphocyte apoptosis but not monocyte THP-1 cells. Ectopic expression of PRMT4 protein caused substantial lymphocyte death via caspase 3-mediated cell death signalling, and knockout of PRMT4 abolished LPS-mediated lymphocyte death. PRMT4 inhibition with a small molecule compound attenuated lymphocyte death in complementary models of sepsis. These findings demonstrate a previously uncharacterised role of a key chromatin modulator in lymphocyte survival that may shed light on devising therapeutic modalities to lessen the severity of septic immunosuppression.


Thin-film solid-state electroluminescent devices based on tris(2,2'-bipyridine)ruthenium(II) complexes.
The behavior of light-emitting electrochemical cells (LEC) based on solid films ( approximately 100 nm) of tris(2,2'-bipyridine)ruthenium(II) between an ITO anode and a Ga-In cathode was investigated. The response times were strongly influenced by the nature of the counterion: small anions (BF(4)(-) and ClO(4)(-)) led to relatively fast transients, while large anions (PF(6)(-), AsF(6)(-)) produced a slow time-response. From comparative experiments of cells prepared and tested in a glovebox to those in ambient, mobility of the anions in these films appears to be related to the presence of traces of water from atmospheric moisture. An electrochemical model is proposed to describe the behavior of these LECs. The simulation results agreed well with experimental transients of current and light emission as a function of time and show that the charge injection is asymmetric at the two electrodes. At a small bias, electrons are the major carriers, while for a larger bias the conduction becomes bipolar.


The integration of family planning and childhood immunization services in Togo.
Improvements in the constellation of services in the African context are largely addressed through attaining better measures of service integration, which can be achieved through improved referral across categories of health programs. The use of an unobtrusive referral message that linked family planning and the Expanded Program of Immunizations (EPI) services was tested in an operations research study in Togo. The introduction of the referral message was accompanied by an 18-percent increase in awareness of available family planning services and an increase in the average monthly number of new family planning clients of 54 percent. These positive results indicate that the use of referral can have a significant and dramatic impact on family planning services in a relatively short time. In Togo, no evidence existed of a negative impact on EPI services, and a majority of the EPI providers reported satisfaction with the effect of the referral message at the close of the study.


[Inhaled nitric oxide in the therapy of acute hypoxemic respiratory failure of newborn].
To determine the efficiency of inhaled nitric oxide(INO) in term and preterm newborns with acute hypoxemic respiratory failure(AHRF), influence of this therapy on the systemic circulation and efficiency of the therapy in relation to the applied ventilation (conventional or oscillatory (HFOV)). Term and preterm ventilated newborns with acute hypoxemic respiratory failure with oxygenation index(OI) >/= 15 were included. The mode of ventilation was not changed before initiation and was continued during INO therapy. Starting dose of INO was 20 parts per million (ppm) and during the last two years it was 1 Oppm. Heart rate, arterial blood pressure, methaemoglobin level, diuresis (in urinary catheterized newborns) were monitored. The efficiency of INO was determined on the ground of 20% decrease of 01. Investigations were performed in 43 term and premature newborns. After initiation of INO there was a statistically significant fall of 01. Therapy was effective in 72.1 % patients. There was no influence of the therapy on the systemic circulation heart rate and medial artery pressure were statistically unchanged. In 16 catheterized newborns statistically essential increase of diuresis was observed. This effect was more distinct in patients in whom INO therapy was effective. INO therapy was more effective in newborns with respiratory distress syndrome, congenital infection and adult respiratory distress syndrome and less effective in newborns with respiratory distress syndrome with congenital infection and meconium aspiration syndrome. There were no essential differences in efficiency of INO between patients ventilated conventionally and oscillatory. INO improves oxygenation in term and preterm newborns with AHRF. INO does not cause depression of the systemic circulation. The increase of diuresis after initiation of INO seems to be associated with improving of oxygenation of the patients. This observation needs to be confirmed by subsequent investigations. The efficacy of INO therapy depends on the cause of hypoxemic respiratory failure. The synergistic effect of INO and HFOV was not confirmed.


A review on chemical mechanism of microalgae flocculation via polymers.
Industrially, harvesting of the microalgal biomass is a techno-economic tailback, which essentially meant for the algal biomass industry. It is considered energy as well as cost-intensive in view of the fact that the dewatering process during harvesting. In this review chemical reactions involved in the flocculation of microalage biomass via various certain principal organic polymers are focused. Besides, it focuses on natural biopolymers as flocculants to harvest the cultivated microalgae. Commercially, bio-flocculation is suitable and cost-effective in the midst of a range of adopted harvesting techniques and the selection of an appropriate bioflocculant depends on its efficacy on the several microalgae strains like potential biomass fixation, ecological stride and non-perilous nature. The harvesting of toxin free microalgae biomass in large quantity by such flocculants can be considered to be one of the most cost-effective performances towards sustainable biomass recovery.


Transcriptional activation in the context of repression mediated by archaeal histones.
Many archaea (including all the methanogens, nearly all euryarchaeotes, and some crenarchaeotes) use histones as components of the chromatin that compacts their genomes. The archaeal histones are homo- and heterodimers that pair on DNA to form tetrasomes (as the eukaryotic histones H3 and H4 do). The resulting DNA packaging is known to interfere with assembly of the archaeal transcription apparatus at promoters; the ability of transcriptional activation to function in repressive archaeal chromatin has not yet been explored in vitro. Using four of the Methanocaldococcus jannaschii (Mja) histones, we have examined activation of the model Mja rb2 transcription unit by the Mja transcriptional activator Ptr2 in this simplified-chromatin context. Using hydroxyl radical footprinting, we find that the Ptr2-specific rb2 upstream activating site is a preferred histone-localizing site that nucleates histone: DNA-binding radiating from the rb2 promoter. Nevertheless, Ptr2 competes effectively with histones for access to the rb2 promoter and most potently activates transcription in vitro at histone concentrations that extensively coat DNA and essentially silence basal transcription.


Assessment of dietary choices of young women in the contexts of hormonal contraceptives
Metabolic changes caused by hormonal contraception combined with unbalanced diet may pose many threats, and deficiency or excess of nutrients may increase the risk of using such contraceptives. The purpose of the survey was to assess the dietary choices of young women using hormonal contraceptives, taking into account their general knowledge about the contraception and its impact on their bodies. The survey comprised 67 women aged from 18 to 25 years. In of three-day menus (201 daily food rations) of the women under research the content of energy and most of nutritious ingredients wandered away from recommended values in Poland. Each respondent additionally filled in a questionnaire concerning her: anthropometric data, education, place of residence; the type, name and time of taking contraceptives; purpose for using hormonal contraception along with its determinants; duration of use, breaks in contraceptive practice; occurrence of side effects during contraceptive use; stimulants used; physical activity, incidence of diarrhoea and vomiting, and dietary supplements use. The assessment of nutritional status of young women taking hormonal contraceptives has shown a number of nonconformities. The survey has revealed insufficient energy value of the menus, and incorrect proportions of basic nutrients, from recommended values, what was reflected in insufficient intake of vitamins (A, D, E, C, B1, B3, B6, and folates) and minerals (K, Ca, Mg, Fe). An excessive consumption of proteins, animal-based in particular, and insufficient consumption of lipids and carbohydrates, polysaccharides in particular, what resulted in insufficient consumption of dietary fibre. Nutritional choices of the respondents were typical to their gender and age, but were not adjusted to the use of hormonal contraceptives. Side effects observed by the respondents, mainly weight gain, may have been a summary result of improper eating behaviors that facilitated accumulation of body fat and water.


Cancer combination therapies with artemisinin-type drugs.
Artemisia annua L. is a Chinese medicinal plant, which is used throughout Asia and Africa as tea or press juice to treat malaria. The bioactivity of its chemical constituent, artemisinin is, however, much broader. We and others found that artemisinin and its derivatives also exert profound activity against tumor cells in vitro and in vivo. Should artemisinin-type drugs be applied routinely in clinical oncology in the future, then it should probably be as part of combination therapy regimens rather than as monotherapy. In the present review, I give a comprehensive overview on synergistic and additive effects of artemisinin-type drugs in combination with different types of cytotoxic agents and treatment modalities: (a) standard chemotherapeutic drugs, (b) radiotherapy and photodynamic therapy, (c) established drugs for other indications than cancer, (d) novel synthetic compounds, (e) natural products and natural product derivatives, (f) therapeutic antibodies and recombinant proteins, and (g) RNA interference. I also summarize the activity of artemisinin-type drugs towards multidrug-resistant cells and tumor cells with other drug resistance phenomena. As synergistic interactions may not only occur in tumor cells, toxic reactions in normal cells (hepatotoxicity, drug interactions) were also considered. This review summarizes the scientific literature of more than 20years until the end of 2016.


Substance P and somatostatin and excitatory neurotransmission in rabbit urinary bladder.
The influence of substance P (SP) and somatostatin (SS) on contractions induced by electrical field stimulation, ATP and carbachol were investigated in isolated rabbit urinary bladder. Some experiments were also carried out in rat and guinea-pig detrusor. When added cumulatively to rabbit and rat preparations, SP and SS caused a gradual increase in tone of the preparations. There were no effects on the electrically induced contractions. In rabbit and rat detrusor pretreated with guanethidine, atropine and indomethacin, the contractile response to nerve stimulation was markedly reduced. In this situation SP and SS caused 2-4 fold increase in the electrically induced contractions. Indomethacin abolished the tonic response to ATP in the rabbit detrusor, and reduced the initial phasic contraction by about 30%. Both SP and SS were able to restore the phasic contraction to the level obtained before indomethacin addition. The contractions induced by carbachol in rabbit and rat detrusor were not affected by SP and SS, not even in indomethacin pretreated preparations. The SP-antagonist (D-Pro2, D-Phe, D-Trp9)-SP was tested in isolated rabbit, rat, and guinea-pig detrusor. Concentrations of the antagonist which effectively inhibited contractions induced by a submaximum concentration of SP had no effect on the contractile response to electrical field stimulation in rabbit and guinea-pig preparations, and rather tended to increase the contractions in the rat detrusor. The results suggest that neither SS nor SP is the mediator of excitatory non-cholinergic, non-adrenergic activation of rabbit urinary bladder. A role as local modulators of neuromuscular transmission cannot be excluded.


Dissecting the localization of Tilapia tilapinevirus in the brain of the experimentally infected Nile tilapia, Oreochromis niloticus (L.).
Tilapia tilapinevirus or tilapia lake virus (TiLV) is an emerging virus that inflicts significant mortality on farmed tilapia globally. Previous studies reported detection of the virus in multiple organs of the infected fish; however, little is known about the in-depth localization of the virus in the central nervous system. Herein, we determined the distribution of TiLV in the entire brain of experimentally infected Nile tilapia. In situ hybridization (ISH) using TiLV-specific probes revealed that the virus was broadly distributed throughout the brain. The strongest positive signals were dominantly detected in the forebrain (responsible for learning, appetitive behaviour and attention) and the hindbrain (involved in controlling locomotion and basal physiology). The permissive cell zones for viral infection were observed mostly to be along the blood vessels and the ventricles. This indicates that the virus may productively enter into the brain through the circulatory system and widen broad regions, possibly through the cerebrospinal fluid along the ventricles, and subsequently induce the brain dysfunction. Understanding the pattern of viral localization in the brain may help elucidate the neurological disorders of the diseased fish. This study revealed the distribution of TiLV in the whole infected brain, providing new insights into fish-virus interactions and neuropathogenesis.


Hydroxyethyl starch pretreatment in bacteremic sheep.
Live bacteria were infused in a chronic ovine lung lymph model to determine if a preceding infusion of the colloid, hydroxyethyl starch (HES), exaggerated the cardiopulmonary dysfunction or impaired removal of bacteria by macrophages in the pulmonary circulation. HES was infused (3 mL/kg/hr; n = 6) from 24 to 12 hr before the bacteria and decreased plasma protein content and increased pulmonary lymph to plasma protein concentration because of its oncotic properties. Ringer's lactate (2 mL/kg/hr) was given after stopping HES and also to the control group (n = 6). Infusion of live Ps. aeruginosa (2.5 x 10(8) Ps./min for approximately 30 min) induced equivalent pulmonary hypertension, increased pulmonary microvascular permeability, and cardiovascular depression in the two groups. The removal of bacteria in the lungs was not affected, indicating that this measurement of the function of the mononuclear phagocytic system was not impaired by the preceding HES.


Fluorescence resonance energy transfer detection of synaptophysin I and vesicle-associated membrane protein 2 interactions during exocytosis from single live synapses.
To investigate the molecular interactions of synaptophysin I and vesicle-associated membrane protein 2 (VAMP2)/synaptobrevin II during exocytosis, we have used time-lapse videomicroscopy to measure fluorescence resonance energy transfer in live neurons. For this purpose, fluorescent protein variants fused to synaptophysin I or VAMP2 were expressed in rat hippocampal neurons. We show that synaptophysin I and VAMP2 form both homo- and hetero-oligomers on the synaptic vesicle membrane. When exocytosis is stimulated with alpha-latrotoxin, VAMP2 dissociates from synaptophysin I even in the absence of appreciable exocytosis, whereas synaptophysin I oligomers disassemble only upon incorporation of the vesicle with the plasma membrane. We propose that synaptophysin I has multiple roles in neurotransmitter release, regulating VAMP2 availability for the soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex and possibly participating in the late steps of exocytosis.


Anthracofibrosis attributed to mixed mineral dust exposure: report of three cases.
Anthracofibrosis, defined as bronchial luminal narrowing with black pigmentation of the overlying mucosa, has been attributed to tuberculosis. Three patients with anthracofibrosis without mycobacterial infection are described who had previous occupational exposure to mixed dusts. CT scans showed calcified hilar lymph nodes in two patients. Surgical biopsy in one patient and autopsy in another revealed fibrotic lymph nodes with black pigmentation. Mineralogical analysis by transmission electron microscopy of pulmonary, hilar and/or bronchial samples found high levels of particle retention, raised percentages of free crystalline silica and mica in two patients, and free crystalline silica, kaolin and other silicates in the third. No evidence of any other contributory factor was found, suggesting that mixed mineral dust was the most probable cause. These observations suggest that exposure to mixed mineral dust should be added to the aetiology of anthracofibrosis.


ZnO nanowire-based UV photodetector.
ZnO nanowire-based ultraviolet (UV) photodetector was proposed and fabricated by depositing interdigitated Au film on vertically well aligned ZnO nanowires. It was found that the deposited Au film form good ohmic contact with the underneath ZnO nanowires. Upon UV irradiation, it was found that the detector current was increased by more than 2.5 times. It was also found that the corresponding time constant for turn-on transient was tau(on) = 3.125 ms while that for turn-off transient was tau(off) = 36.92 ms.


The Digital Bytes Project: Digital Storytelling as a Tool for Challenging Stigma and Making Connections in a Forensic Mental Health Setting.
This article reports on the findings of a study that explores the utility of digital storytelling as a narrative practice and learning tool for social work in an Australian secure forensic mental health hospital. The short digital stories, or Digital Bytes Project, centered on capturing the lived experience, hopes and perspectives of the hospital's service users by giving voice to their experiences through digital technology. The project was collaboratively designed and co-delivered with social work students, hospital staff, and service users. It aimed to not only destigmatize people with lived experiences of mental distress and criminal justice system involvement but also to give staff and students further insights into understanding who they are working with. Through a series of 11 semi-structured, one on one interviews, this research aims to explore social work student and forensic mental health staff experiences and perceptions in relation to the utility and impact of these digital bytes, reflecting on how the prototype bytes may have impacted their learnings, or practice, including how they then interact with service users. This research investigates how these digital bytes could be used further within forensic mental health organisations and contexts. The research findings demonstrate the overall value of digital bytes in challenging different kinds of stigma, shifting power dynamics and staff perspectives; strengthening rapport and understanding through enhancing engagement and sharing power between students, staff, and consumers; as well as providing insight into the utility of digital bytes for learning and making connections between theory and practice. The preliminary findings from this research suggest the need for greater accessibility, integration, and consideration of these digital tools, with their potential to be translated across multiple human service sectors.


ACTH-producing apudoma metastatic to the liver.
A young man presented with combative psychosis and elevated levels of plasma adrenocorticotropic hormone (ACTH). A solitary vascular pancreatic mass and diffuse vascular hepatic nodules were demonstrated on selective splenic and hepatic arteriograms. These classic angiographic findings are used to emphasize the role of angiography in initial radiographic evaluation and to summarize the angiographic appearance of functioning pancreatic adenomas. Even though this is an aggressive tumor, early diagnosis and intensive treatment may allow prolonged remission, if not cure.


Modified Bilston nonlinear viscoelastic model for finite element head injury studies.
This paper proposes a modified nonlinear viscoelastic Bilston model (Bilston et al., 2001, Biorheol., 38, pp. 335-345). for the modeling of brain tissue constitutive properties. The modified model can be readily implemented in a commercial explicit finite element (FE) code, PamCrash. Critical parameters of the model have been determined through a series of rheological tests on porcine brain tissue samples and the time-temperature superposition (TTS) principle has been used to extend the frequency to a high region. Simulations by using PamCrash are compared with the test results. Through the use of the TTS principle, the mechanical and rheological behavior at high frequencies up to 10(4) rads may be obtained. This is important because the properties of the brain tissue at high frequencies and impact rates are especially relevant to studies of traumatic head injury. The averaged dynamic modulus ranges from 130 Pa to 1500 Pa and loss modulus ranges from 35 Pa to 800 Pa in the frequency regime studied (0.01 rads to 3700 rads). The errors between theoretical predictions and averaged relaxation test results are within 20% for strains up to 20%. The FEM simulation results are in good agreement with experimental results. The proposed model will be especially useful for application to FE analysis of the head under impact loads. More realistic analysis of head injury can be carried out by incorporating the nonlinear viscoelastic constitutive law for brain tissue into a commercial FE code.


Emergency treatment of malignant extradural spinal cord compression: an evidence-based guideline.
To review the literature for malignant extradural spinal cord compression (MSCC), produce evidence-based recommendations based on the criteria used by the Canadian Task Force on the Periodic Health Examination, and make suggestions regarding future research directives. A systematic review of the literature with explicit study selection and evaluation criteria was performed. Primary outcome measure was posttreatment ambulation rate. There is good evidence to support the use of high-dose dexamethasone (96 mg/d), but inconclusive evidence for the use of moderate-dose steroids (16 mg/d) in conjunction with radiotherapy (RT) for the treatment of MSCC. Fair evidence exists for not using steroids in patients who are nonparetic and ambulatory pretreatment, and to give radiation to patients with subclinical spinal cord compression (SCC). The remainder of the recommendations are based on inconclusive evidence: RT alone should be the first-line treatment for ambulatory patients except when there is spinal instability, bony compression, or paraplegia on presentation, in which case surgery should be performed. Either modality can be used for paraparetic patients who are nonambulatory. Postoperative RT should be considered for tumor in residua. Ambulatory, undiagnosed patients should have needle biopsy attempted first. Patients should be aggressively screened and educated about SCC. In general, there were very few papers of high methodologic quality found in the literature. More studies are needed to satisfy the validity of many of the clinical decisions that are made today with regard to the management of MSCC.


Supplementation of arachidonic acid rich oil in European sea bass juveniles (Dicentrarchus labrax) diets: Effects on leucocytes and plasma fatty acid profiles, selected immune parameters and circulating prostaglandins levels.
The main objective of this study was to assess the effects of graded levels of dietary arachidonic acid (ARA), supplemented from alternative sources, on fatty acid composition of plasma and head kidney leucocytes of European sea bass (Dicentrarchus labrax). For that purpose, sea bass juveniles were fed four diets containing graded levels of ARA as follows: 0.5% (ARA0.5), 1% (ARA1), 2% (ARA2) and 4% (ARA4) during 60 days. At the end of the feeding trial fatty acid profiles of plasma and head kidney leucocytes were analyzed. Besides, plasma prostaglandins levels, head kidney leucocytes respiratory burst activity; peroxidase activity and phagocytic index were assayed. Reducing dietary ARA levels below 1% markedly reduced European sea bass growth performance. However, fish fed diet ARA0.5 tried to compensate this dietary ARA deficiency by a selective deposition of ARA on plasma and head kidney leucocytes, reaching similar levels to those fish fed diet ARA1 after 60 days of feeding. Nevertheless, head kidney phagocytic capacity was reduced as dietary ARA content in relation not only to variations on membrane composition but also to changes on fish basal prostaglandins levels. Results obtained demonstrated the importance to supply the necessary quantity n-6 LC-PUFA, and not only n-3 LC-PUFA levels, in European sea bass diets, in relation to not only growth performance but also immune system function.


The National Survey on the Constitution and Health of Chinese Students in 1995: Nutritional status of school students aged 10-17 years in Shaanxi, China.
There are 200 million Chinese adolescents and they represent a significant proportion of the world adolescent population. Their health, growth and nutritional status is of vital importance to China but also to the health of adolescents globally. Previous assessments of nutritional status of adolescents in China have been undertaken without using World Health Organization (WHO) recommended anthropometric methods or reference data. Using data from the National Survey on the Constitution and Health of Chinese Students in 1995 (NSCHCS-95), this study aimed to assess the current nutritional status of Shaanxi school students using WHO recommended methods of nutritional assessment. Data for 6284 (3142 females and 3142 males) Shaanxi school students aged 10-17 years was abstracted from the Shaanxi portion of the NSCHCS-95. This national cross-sectional survey gathered anthropometric measurements using standard methods, maturity indicators, and basic social and demographic data. The calculation of anthropometric indicators was based on the National Centre for Health Statistics/WHO reference data and the prevalence of nutritional status indicators was estimated using standard WHO recommended cut-offs and methods of maturity adjustment. The median age of menarche and spermarche was delayed for Shaanxi rural female and male students in comparison with the reference data by 0.81 and 0.39 years, respectively. The prevalence of stunting and thinness in students in almost all ages was higher than in the reference population. For all age groups combined, the adjusted prevalence of stunting was 8.0% for urban students, and 11.0% for rural students. For students under 14 years of age, the adjusted prevalence of thinness was 18.3% for urban students, and 15.1% for rural students. The prevalence of 'at risk of overweight' and obesity among urban male students aged 10-11.99 (for overweight) and 10-12.99 years (for obesity) were similar to the reference population. Undernutrition (stunting and thinness) continues to be a public health problem in the Shaanxi school population and may be related to the less developed rural economy in the province. Young Shaanxi urban male students showed a tendency towards an excess prevalence of 'at risk of overweight' and obesity, which may be related to improved economic conditions in urban areas. It is necessary to develop national anthropometric reference data, cut-off points and median ages of attainment of WHO recommended maturational indicators for Chinese adolescents.


Ruthenium-catalyzed regioselective oxidative coupling of aromatic and heteroaromatic esters with alkenes under an open atmosphere.
A ruthenium-catalyzed oxidative coupling of substituted aromatic and heteroaromatic esters with alkenes in the presence of catalytic amounts of AgSbF(6) and Cu(OAc)(2) to provide highly substituted alkene derivatives in good to excellent yields under an open atmosphere is described.


Idiotypic repertoire of anti-hen eggwhite lysozyme antibodies probed with hybridomas. Selection after immunization of an IdX marker common to antibodies of distinct epitope specificity.
A panel of hybridoma antibodies obtained from lymphoid cells that were fused during a primary response ("early") or a secondary response ("late") gave results concordant with analysis of conventional, in vivo-produced anti-lysozyme idiotypes: early antibodies did not display the predominant anti-hen eggwhite lysozyme idiotype (IdX-HEL), whereas late antibodies all displayed IdX-HEL. Furthermore, individual late hybridomas could each remove the entire anti-IdX-HEL activity by absorption, whereas early hybridomas could not. The epitope specificities of the hybridomas in both the early and late populations were heterogenous. We conclude that epitypic specificity in the response to HEL is determined independently from idiotypic specificity and that the predominant idiotype is selected for during the maturation of the anti-lysozyme response.


Experimental and theoretical evidence of an axially chiral borospherene.
Chirality plays an important role in chemistry, biology, and materials science. The recent discovery of the B40(-/0) borospherenes marks the onset of a class of boron-based nanostructures. Here we report the observation of axially chiral borospherene in the B(39)(-) nanocluster on the bases of photoelectron spectroscopy, global minimum searches, and electronic structure calculations. Extensive structural searches in combination with density functional and CCSD(T) calculations show that B(39)(-) has a C3 cage global minimum with a close-lying C2 cage isomer. Both the C3 and C2 B(39)(-) cages are chiral with degenerate enantiomers. The C3 global minimum consists of three hexagons and three heptagons around the vertical C3 axis. The C2 isomer is built on two hexagons on the top and at the bottom of the cage with four heptagons around the waist. Both the C3 and C2 axially chiral isomers of B(39)(-) are present in the experiment and contribute to the observed photoelectron spectrum. The chiral borospherenes also exhibit three-dimensional aromaticity, featuring σ and π double delocalization for all valence electrons. Molecular dynamics simulations reveal that these chiral B(39)(-) cages are structurally fluxional above room temperature, compared to the highly robust D(2d)B40 borospherene. The current findings add chiral members to the borospherene family and indicate the structural diversity of boron-based nanomaterials.


Multi-Organ Dysfunction Secondary To Yellow Scorpion Sting.
Scorpion stings are common in tropical and subtropical regions. The history and clinical manifestation warrant urgent recognition and treatment. The incidence of scorpion stings in Pakistan is not known as there is no published data available in literature. We report our experience of a yellow scorpion sting victim who required intensive care admission after developing multi-organ dysfunction.


Relationship between smoking and cardiovascular risk factors in the development of peripheral arterial disease and coronary artery disease: Edinburgh Artery Study.
The aim was to determine whether the effect of smoking on the development of peripheral or coronary artery disease might be mediated by other cardiovascular risk factors, including dietary antioxidant vitamin intake, serum low and high density lipoproteins, blood pressure, plasma fibrinogen, blood viscosity and markers of endothelial disturbance and fibrin turnover. 1592 men and women aged 55-74 years were selected at random from 11 general practices in Edinburgh, Scotland and followed-up for 5 years. The incidences of peripheral arterial disease and coronary artery disease were 5.1% and 11.1%, respectively. Both conditions were more common in moderate and heavy smokers than in never smokers: cigarette smoking was a stronger risk factor for peripheral arterial disease than for coronary artery disease. Smoking was associated with reduced dietary antioxidant vitamin intake, serum high density lipoprotein cholesterol and diastolic blood pressure and with increased alcohol intake, serum triglycerides, blood viscosity, plasma fibrinogen, and markers of endothelial disturbance (tissue plasminogen activator and von Willebrand factor antigens). Simultaneous adjustment for these risk factors reduced the relative risk of peripheral arterial disease only slightly, from 3.94 (95% CI 2.04, 7.62) to 2.72 (95% CI 1.13, 6.53) in heavy smokers and from 1.87 (95% CI 0.91, 3.85) to 1.70 (95% CI 0.72, 3.99) in moderate smokers. Similar adjustment also had little effect on the risk of coronary artery disease associated with smoking. The combined effect of smoking on the cardiovascular risk factors studied may explain part of its influence on peripheral and coronary arterial disease, but the majority of the effect appears to be due to other mechanisms.


Ascending to Abdominal Aorta Extraanatomic Bypass for Descending Aortic Coarctation: A Reconstruction Technique without Laparotomy or Left Thoracotomy.
The descending aortic coarctation is often difficult to anatomically reconstruct. We report two cases of ascending aorta to abdominal aorta bypass without laparotomy or thoracotomy. This approach enabled us to avoid anastomosis close to the inflammatory lesion and left thoracotomy causing bleeding from the collateral vessels, and to allow concomitant cardiac procedures to be performed. The graft contact with the intestines can be preventable by the retroperitoneal approach. This technique is useful for the selective patients.


Calmodulin in mammalian nerve.
Calmodulin, a calcium-dependent regulatory protein has been isolated from mammalian nerve. The protein has similarities to the calcium-binding protein earlier shown to be transported at a fast rate in the nerve fibers. The implication is that calmodulin, which has been shown to be involved in various key cellular processes, may have a relation to axoplasmic transport.


Morphogenetic responses of six Philodendron cultivars in vitro.
In vitro morphogenic response of nodal explants from six cultivars of Philodendron viz, blue mistic, painted lady, pink prince, pluto, royal queen and green emperor was studied. Frequency and number of shoot formation depend on the cultivars and concentration of BAP. High frequency and number of shoot formation were obtained w hen the nodal explants were cultured in Nitsch medium supplemented with BAP (6.8-11.8 microM), sucrose (2%) and agar (0.45%), initially in the dark for 8-10 weeks followed by 16 hr photoperiod. Regenerated shoots were rooted on medium without growth regulators. After two weeks of hardening, rooted and rootless shoots were established in the soil with more than 90 and 65% survival rates respectively, while the unhardened plantlets showed a much lower percentage (20%) establishment. A standard protocol for the rapid multiplication of Philodendron is presented.


Tolperisone--a novel modulator of ionic currents in myelinated axons.
The actions of tolperisone on single intact Ranvier nodes of the toad Xenopus were investigated by means of the Hodgkin-Huxley formalism. Adding tolperisone to the bathing medium (100 micromol/l) caused the following fully reversible effects: 1. The sodium permeability P'Na was decreased by about 50% in a nearly potential-independent manner while the so-called sodium inactivation curve was shifted in the negative direction by about 3 mV. 2. The remaining parameters of the sodium system, i.e. m, taum and tauh, did not change. 3. The potassium permeability P'K decreased at strong depolarizing potentials (V > 60 mV); hence the permeability constant P(K) decreased by about 8%. However, weak depolarizations (V < 60 mV) caused P'K to increase by about 7%. 4. The potassium activation curve was shifted in the positive direction by about 9 mV and the exponent of n, b, was reduced from about 3.5 to about 1.5. Concentration-response relations for reduction of the sodium permeability constant PNa and of the potassium permeability constant P(K) yielded apparent dissociation constants of about 0.06 mmol/l and 0.32 mmol/l, respectively. The increase of P'K at V = 40 mV, however, was largely concentration-independent. Our findings show that, in contrast to the prevailing view, tolperisone cannot be said to have a so-called lidocaine-like activity, because its effect on potassium permeability in the threshold region is fundamentally different from that of other known local anaesthetics. We infer that this effect, in combination with the decrease in sodium permeability, is responsible for the tendency of tolperisone to reduce excitability and hence for the antispastic action of tolperisone documented by clinical observations.


Soaking of autografts with vancomycin is highly effective on preventing postoperative septic arthritis in patients undergoing ACL reconstruction with hamstrings autografts.
To evaluate the impact of local soaking of the autografts with vancomycin during anterior cruciate ligament (ACL) reconstruction on postoperative infection rates. Between 2003 and 2014 (first study period), 1,242 patients underwent ACL reconstruction using autografts, without soaking them in vancomycin solution, while between 2014 and 2019 (second study period) all ACL autografts in 593 patients were soaked in a 5-mg/ml vancomycin solution, in a territory University Hospital. The same standard treatment of perioperative IV antibiotics was applied in both groups. Postoperative septic arthritis occurred in seven out of 1,242 patients (0.56%) during the first study period. Bone patellar tendon bone autograft was used in 311 (25%) patients, and hamstring tendon autograft was used in the rest 931 (75%) of the study population during this period. All infected cases were male and had a hamstrings graft implanted. There were no postoperative infections (0%) in 593 ACL reconstructions during the second study period. Bone patellar tendon bone autograft was used in 178 (30%) patients while hamstring tendon autograft was used in the rest 415 (70%) of the study population, during this period. Statistical analysis revealed a significantly reduced postoperative infection rate (p = 0.018) between the two reported periods, with the main impact referring to the use of hamstrings autograft (p = 0.031) for the first study period. Septic arthritis following ACL reconstruction can be significantly reduced (or even eliminated) by soaking ACL autografts in a 5 mg/ml vancomycin solution. Of note, this strategy seems to be more effective in the setting of hamstring tendon autograft use, since the risk of postoperative knee infection is significantly higher when this type of graft is used.


Reconstruction of frontal defects with calvarial grafts.
There are many options for the reconstruction of frontal sinus wall defect resulting from injury, neoplastic lesions and aesthetic deformities. These mainly include autogenous grafts, allogenous grafts, and alloplastic materials. The aim of the present study is to report the advantages of using autogenous calvarial bone grafts over other reconstruction techniques, in the reconstruction of frontal defects. We describe 16 consecutive cases of anterior frontal sinus defects between 2004 and 2015, in which calvarial bone grafts were used. Medical records were retrospectively analysed to evaluate graft survival. Bone defects were caused by injury (3), aesthetic deformities (2), external frontal sinus surgeries (2), tumours (6: three osteomas, two fibrous dysplasias, one squamous cell carcinoma), and osteomyelitis (3). There were no significant complications during harvesting, and morbidity was minimal. Furthermore, at one and five-year follow-up, no graft resorption or rejection was noted, and cosmetic results were satisfactory. Our results indicate that calvarial bone graft is an appropriate material to use in anterior frontal sinus reconstruction.


Hypoxia regulates CD44 expression via hypoxia-inducible factor-1α in human gastric cancer cells.
Hypoxia induces proliferation and invasion in cancer cells via hypoxia-inducible factor (HIF)-1α. The cell adhesion molecule cluster of differentiation (CD) 44 has been associated with increased cell invasion and metastasis. Whether hypoxia regulates the expression of CD44 in gastric cancer cells remains to be established. In the current study, the effects of hypoxia on HIF-1α and CD44 expression levels in human gastric cell lines SGC-7901 and BGC-823 were evaluated. The cells were cultured in 1% O2 for 1 week and then treated with 20 nM rapamycin for 72 h. Cell viability was evaluated using the Cell Counting kit-8 assay, and cell invasion was detected by the Transwell invasion assay. The protein and messenger (m) RNA expression levels of HIF-1α and CD44 were detected using western blotting and reverse transcription-quantitative polymerase chain reaction, respectively. The results revealed that cell viability and invasion increased under hypoxic conditions, but decreased following rapamycin treatment in SGC-7901 and BGC-823 cells. Hypoxia also increased the protein and mRNA expression levels of HIF-1α and CD44 in these two cell lines. However, this hypoxia-induced increase in HIF-1α and CD44 protein and mRNA expression levels was inhibited by rapamycin. These findings suggest that hypoxia induced the proliferation and invasion of SGC-7901 and BGC-823 cells. Furthermore, CD44 expression levels were potentially associated with HIF-1α expression levels. Therefore, in gastric cancer cells, hypoxia may regulate CD44 expression via HIF-1α in order to promote cell proliferation and invasion.


Proinflammatory effects of photoactivated methylene blue on rat model of Walker 256 carcinosarcoma.
Photodynamic therapy (PDT) is an anticancer therapy that associates the photosensitizer (PS), oxygen and light to destroy cancer cells. Methylene blue (MB) is considered a second generation phenothiazine dye with excellent photochemical properties. To evaluate whether MB-mediated PDT can induce oxidative stress and inflammation, therefore, interfering tumor growth. The study was conducted on Wistar rats transplanted with Walker 256 carcinosarcoma (W256). The proinflammatory interleukins levels (IL-1β, IL-6, IL-10, TNF-α) were determined by ELISA, mRNA expression of COX-1, COX-2, iNOS and eNOS by RT-PCR, lipid peroxidation was measured by the TBARS method. Moreover, myeloperoxidase (MPO) activity in neutrophils was determined by MPO activity assay. All indices mentioned above were determined in tumor tissue. Kaplan - Meier and Gehan - Breslow - Wilcoxon tests were used for survival analysis. We found that the treatment of W256 with 0.1% MB + 1 J/cm2 provoked a significant increase in the interleukins levels (IL-1β, IL-6, IL-10, TNF-α), prostaglandin E2, the mRNA expression of COX-2, iNOS, lipid peroxidation and MPO activity in tumor tissue, which were statistically different (p < 0.05) compared to other experimental and control groups. The results of the estimation of survival curves show a greater probability of survival in 0.1% MB + 1 J/cm2 (total energy dose =142.8 J/cm2) treated group. Our results suggest that treatment of W256 with 0.1% MB + 1 J/cm2 was able to promote cytotoxic effects in tumor tissue by the generation of reactive oxygen species causing inflammation and thus interfering in the tumor growth.


Spouse's Cardiovascular Disease As a Risk Factor for Cardiovascular Disease in Middle-Aged Adults: A Matched-Pair Cohort Study.
Little is known about the risk of subsequent cardiovascular events in individuals whose spouse has a history of cardiovascular diseases. We assessed whether the spouse's history of cardiovascular disease is associated with a greater risk of cardiovascular events. Using data on married couples from the Japan Medical Data Center database (April 2008-August 2018), we conducted a matched-pair cohort study by matching individuals who had no history of cardiovascular disease and whose spouse had a history of cardiovascular disease at their first health check-up (exposure group) with up to 4 individuals who had no history of cardiovascular disease and whose spouse had no history of cardiovascular disease at their first health check-up (nonexposure group) matched for birth year, sex, and first health check-up year. We compared severe cardiovascular events after the first health check-up between the 2 groups. Among 236 527 eligible married couples (473 054 spouses), we identified 13 759 individuals in the exposure group who were matched with 55 027 individuals in the nonexposure group. During the mean 95-month observational period from the first health check-up, the percentage of individuals with severe cardiovascular events was higher in the exposure group than in the nonexposure group (0.6% [82/13 759] versus 0.4% [224/55 027], respectively), with a hazard ratio of 1.48 (95% CI, 1.15-1.90). Analyses stratified by sex showed that the hazard ratios of the exposure to the spouse's history of cardiovascular disease for severe cardiovascular events in women and men were 1.22 (95% CI, 0.82-1.83) and 1.68 (95% CI, 1.22-2.32), respectively. This study suggests that a spouse's history of cardiovascular disease can be a risk factor for subsequent cardiovascular events in men but not in women. Further studies are needed to confirm our findings and to explore effective primary prevention strategies for these individuals.


[Development of the osseous structures of internal ear in human foetuses].
Assessment of development of selected osseous structures of internal ear (cochlea, vestibule, modiolus) in human foetuses aged between 9-32 weeks was the aim of this study. Human osseous labyrinth is a very interesting albeit difficult research subject. Current study represents a trial to summarize the knowledge about its development in prenatal period available so far. At the same time it underlines the importance of research on the development of ear's structures for prevention of hearing disorders as well as for their early development and treatment. Descriptive methods: macroscopic, radiological, anthropometric and histological were used in this study. The presence of arcuate eminence as well as subarcuate fossa was established which proves the development of osseous labyrinth inside the petrous part of temporal bone. Points of ossification of the otic capsule were described. Highest dynamics of development and abundance of morphological forms was found in the II group of foetuses including those between 18-24 week of intrauterine life.


I. Carcinoma of the rectum and rectosigmoid: cancer specific long-term survival. A series of 1061 cases treated by one surgeon.
The long-term cancer specific survival based on individual follow-up and analysis of prospectively collected data from 1061 patients undergoing resection for carcinoma of the rectum is presented. All patients were operated on and managed by one surgeon. Survival data for 978 cases were analyzed according to the methods of Kaplan and Meier, and Gehan. Results have been presented as cancer specific survival times in months and as percentage survivor rates at five-year intervals. The median overall cancer specific survival time was 96 months. Five, ten, 15, and 20-year survival rates were 56, 49, 47, and 46%, respectively. After a potentially curative resection of the tumor, the corresponding percentages were 69, 60, 57, and 56%. Age and sex were not significant prognostic factors. A death rate from recurrent cancer of nil was seen after 15.4 years. At this point, the cancer specific survival rates were 77% for patients in Stage A, 59% in Stage B, 37% in Stage C, and 9% for patients with tumors invading adjacent organs (D1), while no patient with macroscopic metastases to distant organs (Stage D2) survived beyond four and a half years (median, 11 months).


IL-36β Promotes Inflammatory Activity and Inhibits Differentiation of Keratinocytes In Vitro.
Objective Psoriasis is an immune-mediated inflammatory disease. Despite advances in the study of its pathogenesis, the exact development mechanism of psoriasis remains to be fully elucidated. Hyperproliferative epidermis plays a crucial role in psoriasis. This study aimed to investigate the effects of interleukin-36β (IL-36β) on keratinocyte dysfunction in vitro. Methods Human keratinocyte cell lines, HaCaT cells, were treated with 0 (control), 50 or 100 ng/ml IL-36β respectively for 24 h. Cell viability was determined with a cell counting kit-8 assay. Flow cytometry was used to assess the effects of IL-36β on apoptosis and cell cycle distribution. Expressions of the differentiation markers, such as keratin 10 and involucrin, were evaluated by quantitative real-time polymerase chain reaction (RT-qPCR). Expressions of the inflammatory cytokines, IL-1β and IL-6 were tested by ELISA. Results CCK8 assay showed the survival rate had no significant difference between the control and treated group (P > 0.05). Flow cytometry analysis showed cell cycle arrest at S phase in the IL-36β-treated groups compared with the control group (P < 0.05). RT-qPCR verified the decreased mRNA expressions of keratin 10 and involucrin in the IL-36β-treated groups compared with the negative control (P < 0.01). ELISA showed 100 ng/ml IL-36β enhanced levels of IL-1β and IL-6 in culture supernatants of HaCaT cells compared with the negative control (P < 0.05). Conclusion Taken together, these findings suggest that IL-36β could induce cell cycle arrest at S phase, inhibit keratin 10 and involucrin expressions and promote inflammatory activity in HaCaT cell lines.


Memory training for adults with probable mild cognitive impairment: a pilot study.
Background & Objectives: This pilot study aimed to evaluate the efficacy of memory training and health training intervention over a 24-month period in people with probable mild cognitive impairment (MCI). Research Design & Methods: Based on the accepted criteria, and the neuropsychiatric measures used in the trial, MCI was defined as a subjective change in cognition, impairment in episodic memory, preservation of independence of functional abilities, and no dementia. Without a neurological assessment, laboratory tests, and psychometric evaluation combined, some of our participants may have had dementia that we were unable to detect through neuropsychological testing. Of the 263 total participants, 39 met criteria for a diagnosis of MCI. There were 19 adults in the memory and 20 in health training conditions. Both groups received twenty hours of classroom content that included eight hours of booster sessions at three months post intervention. Hierarchical linear models (HLM) and standardized regression-based (SBR) analyses were used to test the efficacy of the intervention on immediate recall, delayed recall, subjective memory complaints, and memory self-efficacy. Age, education, depression, racial group, ethnic group, MMSE score, and baseline performance were included as covariates. Results: Over 24 months, the MCI group in the memory training condition showed better objective and subjective memory outcomes compared with the MCI group in the health training condition. Conclusions: Senior WISE Memory training delivered to individuals with MCI was able to forestall the participants' declining cognitive ability and sustain the benefit over two years in both subjective and objective memory function.


Detection of a COVID-19 cluster by universal SARS-CoV-2 testing in a geriatric hospital and implications for infection control management.
Hospital-level COVID-19 testing strategies may require rapid changes depending on the dynamics of local epidemiology. A COVID-19 outbreak in a hospital near the authors' institution, a Geriatric Medicine centre in Berlin, Germany, prompted the implementation of comprehensive SARS-CoV-2 testing. Serial nasopharyngeal swabs were collected from all patients and staff and analysed for SARS-CoV-2 virus RNA using quantitative real-time PCR. In total, 11 of 84 patients (13.1%) and 1 of 147 employees (0.68%) tested positive. Of the 11 positive patients, 9 (81.8%) were asymptomatic at the time of testing. The data were used as the basis for adjusting local COVID-19 containment measures. Only one staff-to-staff transmission was observed, and there was no patient-to-patient, patient-to-staff or staff-to-patient transmission. Three patients infected with SARS-CoV2 died, two deaths being attributable to advanced malignant disease and one to COVID-19-associated myocarditis. In conclusion, universal SARS-CoV-2 testing revealed a cluster of predominantly asymptomatic infections, enabled appropriate local COVID-19 containment decisions and presumably contributed to the prevention of in-hospital SARS-CoV-2 transmission.


Influence of cytarabine metabolic pathway polymorphisms in acute myeloid leukemia induction treatment.
Cytarabine is considered the most effective chemotherapeutic option in acute myeloid leukemia (AML). The impact of 10 polymorphisms in cytarabine metabolic pathway genes were evaluated in 225 adult de novo AML patients. Variant alleles of DCK rs2306744 and CDA rs602950 showed higher complete remission (p = .024, p = .045), with lower survival rates for variant alleles of CDA rs2072671 (p = .015, p = .045, p = .032), rs3215400 (p = .033) and wild-type genotype of rs602950 (p = .039, .014). Induction death (p = .033) and lower survival rates (p = .021, p = .047) were correlated to RRM1 rs9937 variant allele. In addition, variant alleles of CDA rs532545 and rs602950 were related to skin toxicity (p = .031, p = .049) and mucositis to DCK rs2306744 minor allele (p = .046). Other toxicities associated to variant alleles were hepatotoxicity to NT5C2 rs11598702 (p = .032), lung toxicity (p = .031) and thrombocytopenia to DCK rs4694362 (p = .046). This study supports the interest of cytarabine pathway polymorphisms regarding efficacy and toxicity of AML therapy in a coherent integrated manner.


Clinical and economic impact of remote monitoring on the follow-up of patients with implantable electronic cardiovascular devices: an observational study.
Traditional follow-up of patients with cardiovascular devices is still an activity that, in addition to serving an increasing population, requires a considerable amount of time and specialized human and technical resources. Our aim was to evaluate the applicability of the CareLink(®) (Medtronic, Minneapolis, MN) remote monitoring system as a complementary option to the follow-up of patients with implanted devices, between in-office visits. Evaluated outcomes included both clinical (event detection and time to diagnosis) and nonclinical (patient's satisfaction and economic costs) aspects. An observational, longitudinal, prospective study was conducted with patients from a Portuguese central hospital sampled by convenience during 1 week (43 patients). Data were collected in four moments: two in-office visits and two remote evaluations, reproducing 1 year of clinical follow-up. Data sources included health records, implant reports, initial demographic data collection, follow-up printouts, and a questionnaire. After selection criteria were verified, 15 patients (11 men [73%]) were included, 63.4±10.8 years old, representing 14.0±6.3 implant months. Clinically, 15 events were detected (9 by remote monitoring and 6 by patient-initiated activation), of which only 9 were symptomatic. We verified that remote monitoring could detect both symptomatic and asymptomatic events, whereas patient-initiated activation only detected symptomatic ones (p=0.028). Moreover, the mean diagnosis anticipation in patients with events was approximately 58 days (p<0.001). In nonclinical terms, we observed high or very high satisfaction (67% and 33%, respectively) with using remote monitoring technology, but still 8 patients (53%) stated they preferred in-office visits. Finally, the introduction of remote monitoring technology has the ability to reduce total follow-up costs for patients by 25%. We conclude that the use of this system constitutes a viable complementary option to the follow-up of patients with implantable devices, between in-office visits.


Postcoital intra-uterine aspirate--a unique criterion for selecting patients for natural or assisted conception.
The success of any infertility management programme is reflected in its efficacy to achieve a pregnancy either spontaneously or through assistance. For this purpose some routine investigations are carried out to pinpoint the nature of problem(s) which an infertile couple is troubled with. As the basic requisite for conception to occur is the accumulation of motile spermatozoa around the egg at the site of fertilisation, proper assessment of sperm transit from the vagina to the tubal ampulla becomes a very important criterion to predict the possibility of spontaneous pregnancy. Till date postcoital test was the sole investigative tool available to serve this purpose but unfortunately it fails to furnish any information about the concentration and nature of quality of spermatozoa beyond the cervix. This results in the disparity between postcoital test results and pregnancy outcome. In the present study intra-uterine fluid was examined along with cervical mucus 4-6 hours postcoitus in the pre-ovulatory period. The objective was to gather information about the fate of spermatozoa subjected to the uterine environment after being vaginally deposited during coitus. The result of this combined test has been found to be very much informative and helpful for the fertility physician to set the criteria for timed intercourse and / or intra-uterine insemination. This simple test thus appears to play a leading role in infertility management in near feature.


Dynamically Switchable Multicolor Electrochromic Films.
The dynamic optical switch of plasmonic nanostructures is highly desirable due to its promising applications in many smart optical devices. To address the challenges in the reversibility and transmittance contrast of the plasmonic electrochromic devices, here, a strategy is reported to fabricate color switchable electrochromic films through electro-responsive dissolution and deposition of Ag on predefined hollow shells of Au/Ag alloy. Using the hollow Au/Ag alloy nanostructures as stable seeds for site-specific deposition of Ag, elimination of the random self-nucleation events is enabled and optimal reversibility in color switching is allowed. The hollow structure further enables excellent transmittance contrast between the bleached and colored states. With its additional advantages such as the convenience for preparation, high sensitivity, and field-tunable optical property, it is believed that this new electrochromic film represents a unique platform for designing novel smart optical devices.


[Enzyme replacement therapy: a new treatment concept in Gaucher disease].
Until recently the treatment of lysosomal storage disorders was entirely supportive. A new enzyme replacement therapy has become available in Gaucher's disease, a lipid storage disorder that is due to a genetic defect of beta-glucocerebrosidase. Intravenous infusions of modified beta-glucocerebrosidase has produced clinical improvement in Gaucher patients, with regression of organomegaly and increase in blood counts. At the Children's Hospital of Mainz 13 patients (6 children and 7 adults) were treated with alglucerase on a high-dosage regimen (60 units per kilogram every two weeks). A decrease in liver and spleen size was observed 4 to 6 months after commencement of therapy. Hemoglobin and the number of platelets increased. In some cases, a reduction of the dosage was possible after a year of enzyme replacement-therapy. A growth spurt was observed in the children. The availability of enzyme replacement therapy is limited by its high cost; however, in the future gene transfer may become the treatment of choice.


Relation between cubic-difference-tone generation and suppression.
Two aspects of the relation between cubic-difference-tone (CDT) generation and suppression were investigated in normal hearing listeners. First, the effects of narrow-band noise and sinusoids on the two processes were examined using a forward-masking paradigm. Within individual listeners, cubic difference bands (CDBs) behaved much like CDTs whereas the suppression effects produced by narrow-band noise were substantially less than those produced by sinusoids. These results suggest that at least partially different processes underlie the two the two phenomena. Second, the role of suppression in the difference between forward- and simultaneous-masking estimates of CDB amplitude was investigated. The data across listeners were highly variable but indicated a more complicated interpretation than that proposed by Shannon and Houtgast [J. Acoust. Soc. Am. 68, 825-829 (1980)].


The E2 ubiquitin conjugase Rad6 is required for the ArgR/Mcm1 repression of ARG1 transcription.
Transcription of the Saccharomyces cerevisiae ARG1 gene is under the control of both positive and negative elements. Activation of the gene in minimal medium is induced by Gcn4. Repression occurs in the presence of arginine and requires the ArgR/Mcm1 complex that binds to two upstream arginine control (ARC) elements. With the recent finding that the E2 ubiquitin conjugase Rad6 modifies histone H2B, we examined the role of Rad6 in the regulation of ARG1 transcription. We find that Rad6 is required for repression of ARG1 in rich medium, with expression increased approximately 10-fold in a rad6 null background. Chromatin immunoprecipitation analysis indicates increased binding of TATA-binding protein in the absence of Rad6. The active-site cysteine of Rad6 is required for repression, implicating ubiquitination in the process. The effects of Rad6 at ARG1 involve two components. In one of these, histone H2B is the likely target for ubiquitination by Rad6, since a strain expressing histone H2B with the principal ubiquitination site converted from lysine to arginine shows a fivefold relief of repression. The second component requires Ubr1 and thus likely the pathway of N-end rule degradation. Through the analysis of promoter constructs with ARC deleted and an arg80 rad6 double mutant, we show that Rad6 repression is mediated through the ArgR/Mcm1 complex. In addition, analysis of an ada2 rad6 deletion strain indicated that the SAGA acetyltransferase complex and Rad6 act in the same pathway to repress ARG1 in rich medium.