Shift-symmetric configurations in two-dimensional cellular automata: Irreversibility, insolvability, and enumeration.
The search for symmetry, as an unusual yet profoundly appealing phenomenon, and the origin of regular, repeating configuration patterns have long been a central focus of complexity science and physics. To better grasp and understand symmetry of configurations in decentralized toroidal architectures, we employ group-theoretic methods, which allow us to identify and enumerate these inputs, and argue about irreversible system behaviors with undesired effects on many computational problems. The concept of so-called "configuration shift-symmetry" is applied to two-dimensional cellular automata as an ideal model of computation. Regardless of the transition function, the results show the universal insolvability of crucial distributed tasks, such as leader election, pattern recognition, hashing, and encryption. By using compact enumeration formulas and bounding the number of shift-symmetric configurations for a given lattice size, we efficiently calculate the probability of a configuration being shift-symmetric for a uniform or density-uniform distribution. Further, we devise an algorithm detecting the presence of shift-symmetry in a configuration. Given the resource constraints, the enumeration and probability formulas can directly help to lower the minimal expected error and provide recommendations for system's size and initialization. Besides cellular automata, the shift-symmetry analysis can be used to study the nonlinear behavior in various synchronous rule-based systems that include inference engines, Boolean networks, neural networks, and systolic arrays.


Nerve Torsion as a Pattern of Parsonage-Turner Syndrome: Literature Review and Two Representative Cases.
(1) Background: Parsonage-Turner Syndrome (PTS) is a rare peripheral nerve disease characterized by different degrees of nerve impairment. The recent development of nerve ultrasound has enabled the use of new data in the diagnosis of the disease. The aim of this study is to conduct a literature review about the ultrasound evaluation of PTS and present two clinical cases that are characteristic of the disease. (2) Methods: A review of the literature from the last 10 years on the topic containing data regarding nerve ultrasound was performed. In addition, two cases of patients on whom nerve ultrasound was performed at the first evaluation and at follow-up after the indicated treatment were described. (3) Results: The results of our review show that although it is defined as plexopathy, PTS is most often a form of multifocal neuropathy. We also report the most frequently used ultrasound classification and possible prognostic correlations and report our experience with the description of two paradigmatic clinical cases. (4) Conclusions: Further studies are needed to understand the true prognostic power of each degree of nerve impairment and the possible implications in clinical practice regarding treatment indications.


Self-assembled monolayer and multilayer films of the nanocluster [HxPMo12O40 subsetH4Mo72Fe30(O2CMe)15O254(H2O)68] on gold.
Films of the molybdenum-iron nanocluster [H x PMo 12O 40 subsetH 4Mo 72Fe 30(O 2CMe) 15O 254(H2O) 68] (FeMoC) were generated on gold via the self-assembly technique using two divergent routes. The first route entails the self-assembly of unfunctionalized FeMoC onto a preprepared carboxyl-terminated SAM on gold. The second route involves the preparation of thiol-terminated functionalized FeMoC clusters, which are then allowed to self-assemble onto bare gold surfaces. Monolayer films of FeMoC clusters are attained via both routes, with the second route requiring shorter immersion times (2 days) than the first route (6 days). Multilayer films of FeMoC are formed via the second route for immersion times longer than 2 days. Characterization of these films using optical ellipsometry, X-ray photoelectron spectroscopy, and atomic force microscopy confirm the self-assembly of the clusters on the surfaces.


Synthesis and oxidation behavior of 2,4,5,7,8-pentamethyl-4H-1,3-benzodioxin-6-ol, a multifunctional oxatocopherol-type antioxidant.
2,4,5,7,8-Pentamethyl-4H-1,3-benzodioxin-6-ol (PBD, 1) is a novel 3-oxa-tocopherol-type stabilizer, which is obtained as a mixture of two diastereomers by condensation of trimethylhydroquinone with acetaldehyde in an acid-catalyzed reaction. The oxidation behavior of 1 is governed by the amount of water available. In aqueous media, 1 is oxidized by one oxidation equivalent to 2,5-dihydroxy-3,4,6-trimethylacetophenone (3) via 2-(1-hydroxyethyl)-3,5,6-trimethylbenzo-1,4-quinone (2). The acid-catalyzed conversion of 2 into 3 proceeds in solution with first-order kinetics with regard to 2 but works also in solid phase. Oxidation in the presence of just 1 equiv of water produces acetophenone 3 as well, but according to a different mechanism involving o-quinone methide 5 and styrene derivative 6, from which finally acetaldehyde is released. A [1,5]-sigmatropic proton shift from the C-4a methyl group to the exocyclic methylene group in 5 causes formation of 6, as demonstrated by labeling experiments. In addition, the presence of both intermediates was proven by hetero-Diels-Alder trapping reactions. In the absence of water, oxidation of 1 produces chromenone 10 via the intermediates 5 and 6 and chromanone 9, and oxidation of 9 to 10 is preferred to oxidation of starting material 1. When the formation of an exocyclic methylene group at C-4 is impossible as a result of structural prerequisites, as in the diphenyl derivative 12, the initially generated o-quinone methide 5 cannot form 6 but undergoes dimerization to spiro-compounds. The transformation of p-quinone 2 into acetophenone 3 might contribute to the chemistry of tocopherols oxidized at C-4, i.e., 4-hydroxy-alpha-tocopherol and 4-oxo-alpha-tocopherol, which have been proposed as precursors of natural vitamin E metabolites.


Insufficient effort responding: examining an insidious confound in survey data.
Insufficient effort responding (IER; Huang, Curran, Keeney, Poposki, & DeShon, 2012) to surveys has largely been assumed to be a source of random measurement error that attenuates associations between substantive measures. The current article, however, illustrates how and when the presence of IER can produce a systematic bias that inflates observed correlations between substantive measures. Noting that inattentive responses as a whole generally congregate around the midpoint of a Likert scale, we propose that Mattentive, defined as the mean score of attentive respondents on a substantive measure, will be negatively related to IER's confounding effect on substantive measures (i.e., correlations between IER and a given substantive measure will become less positive [or more negative] as Mattentive increases). Results from a personality questionnaire (Study 1) and a simulation (Study 2) consistently support the hypothesized confounding influence of IER. Using an employee sample (Study 3), we demonstrated how IER can confound bivariate relationships between substantive measures. Together, these studies indicate that IER can inflate the strength of observed relationships when scale means depart from the scale midpoints, resulting in an inflated Type I error rate. This challenges the traditional view that IER attenuates observed bivariate correlations. These findings highlight situations where IER may be a methodological nuisance, while underscoring the need for survey administrators and researchers to deter and detect IER in surveys. The current article serves as a wake-up call for researchers and practitioners to more closely examine IER in their data.


New twist on neuronal insulin receptor signaling in health, disease, and therapeutics.
Long after the pioneering studies documenting the existence of insulin (year 1967) and insulin receptor (year 1978) in brain, the last decade has witnessed extraordinary progress in the understanding of brain region-specific multiple roles of insulin receptor signalings in health and disease. In the hypothalamus, insulin regulates food intake, body weight, peripheral fat deposition, hepatic gluconeogenesis, reproductive endocrine axis, and compensatory secretion of counter-regulatory hormones to hypoglycemia. In the hippocampus, insulin promotes learning and memory, independent of the glucoregulatory effect of insulin. Defective insulin receptor signalings are associated with the dementia in normal aging and patients with age-related neurodegenerative diseases (e.g., Alzheimer's disease); the cognitive impairment can be reversed with systemic administration of insulin in the euglycemic condition. Intranasal administration of insulin enhances memory and mood and decreases body weight in healthy humans, without causing hypoglycemia. In the hypothalamus, insulin-induced activation of the phosphoinositide 3-kinase pathway followed by opening of ATP-sensitive K+ channel has been shown to be related to multiple effects of insulin. However, the precise molecular mechanisms of insulin's pleiotropic effects still remain obscure. More importantly, much remains unknown about the quality control mechanisms ensuring correct conformational maturation of the insulin receptor, and the cellular mechanisms regulating density of cell surface functional insulin receptors.


Dextroversion due to giant left atrium in a child.
Giant left atrium is extremely rare in pediatric population. We hereby report a case of 4-year-old child with giant left atrium (LA) due to "non-rheumatic" mitral regurgitation (MR). The giant LA caused dextro-rotation of the heart, which immediately reverted to normal cardiac position after surgical repair. The case is reported for the unusual manifestation of giant LA as dextroversion.


Nocturnal glucose control with an artificial pancreas at a diabetes camp.
Recent studies have shown that an artificial-pancreas system can improve glucose control and reduce nocturnal hypoglycemia. However, it is not known whether such results can be replicated in settings outside the hospital. In this multicenter, multinational, randomized, crossover trial, we assessed the short-term safety and efficacy of an artificial pancreas system for control of nocturnal glucose levels in patients (10 to 18 years of age) with type 1 diabetes at a diabetes camp. In two consecutive overnight sessions, we randomly assigned 56 patients to receive treatment with an artificial pancreas on the first night and a sensor-augmented insulin pump (control) on the second night or to the reverse order of therapies on the first and second nights. Thus, all the patients received each treatment in a randomly assigned order. The primary end points were the number of hypoglycemic events (defined as a sensor glucose value of <63 mg per deciliter [3.5 mmol per liter] for at least 10 consecutive minutes), the time spent with glucose levels below 60 mg per deciliter (3.3 mmol per liter), and the mean overnight glucose level for individual patients. On nights when the artificial pancreas was used, versus nights when the sensor-augmented insulin pump was used, there were significantly fewer episodes of nighttime glucose levels below 63 mg per deciliter (7 vs. 22) and significantly shorter periods when glucose levels were below 60 mg per deciliter (P=0.003 and P=0.02, respectively, after adjustment for multiplicity). Median values for the individual mean overnight glucose levels were 126.4 mg per deciliter (interquartile range, 115.7 to 139.1 [7.0 mmol per liter; interquartile range, 6.4 to 7.7]) with the artificial pancreas and 140.4 mg per deciliter (interquartile range, 105.7 to 167.4 [7.8 mmol per liter; interquartile range, 5.9 to 9.3]) with the sensor-augmented pump. No serious adverse events were reported. Patients at a diabetes camp who were treated with an artificial-pancreas system had less nocturnal hypoglycemia and tighter glucose control than when they were treated with a sensor-augmented insulin pump. (Funded by Sanofi and others; ClinicalTrials.gov number, NCT01238406.).


Development and application of a radioimmunoassay for pepleomycin.
A rapid sensitive radioimmunoassay for pepleomycin (PM) has been developed using an antiserum produced in a sheep in response to a bovine serum albumin-drug conjugate. Radioiodinated PM was prepared using Iodogen. The assay was reproducible with a limit of detection in plasma of 200 ng/liter. The antiserum does not cross-react with bleomycin or with a number of unrelated drugs. Pharmacokinetic studies using the assay were carried out in three patients who received a short iv infusion of 5 mg/m2 of PM. The drug disappeared from the plasma with an elimination half-life of approximately 3 hours.


Identification of human papillomavirus type 18 E6 polypeptide in cells derived from human cervical carcinomas.
We recently reported the expression of human papillomavirus type 18 (HPV-18) E6 protein in bacteria and the production of anti-E6 polyclonal antibodies. This work has now been extended with the production of a panel of monoclonal antibodies against the HPV-18 E6 protein. These antibodies demonstrate that there is little antigenic conservation in the E6 protein between HPV-16 and HPV-18, with only one antibody recognizing a cross-reactive epitope. We have used both the monoclonal and the polyclonal antibodies to look for E6 expression in a number of HPV DNA-containing cell lines. These reagents specifically detected a 16.5K mol. wt. polypeptide in cells derived from a human cervical carcinoma.


Comparing Adrenaline with Tranexamic Acid to Control Acute Endobronchial Bleeding: A Randomized Controlled Trial.
Hemoptysis occurs due to either pulmonary diseases or bronchoscopy interventions. The aim of the present study was to compare the efficacy of the endobronchial instillation of adrenaline with that of tranexamic acid. Fifty patients were randomly selected as 2 double-blinded sample groups (n=25). In these patients, bleeding could not be controlled with cold saline lavage during bronchoscopy and they, therefore, required prescription of another medicine. Adrenaline (1 mg) in one group and tranexamic acid (500 mg) in the other group were diluted in 20 mL of normal saline and instilled through the bronchoscope. This technique was repeated 3 times at 90-second intervals, if necessary. In the case of persistent bleeding, 90 seconds after the last dose, a second medicine was given for bleeding control. Observation of clot through the bronchoscope meant that the bleeding had stopped. The efficacy of tranexamic acid and adrenaline was evaluated and then compared using the Mann-Whitney test. The time of bleeding control had no significant difference between tranexamic acid and adrenaline (P=0.908). Another analysis was done to evaluate bleeding control with a second medicine; the results showed that 1 (4%) patient in the tranexamic acid and 8 (32%) in the adrenaline group needed the second medicine and there was no significant difference between the 2 groups (P=0.609). Our results suggested that tranexamic acid by endobronchial instillation was as efficient as adrenaline in controlling hemoptysis and required less frequent use of a second medicine. Trial Registration Number: IRCT2014120220188.


Effect of TCDD exposure in adult female and male mice on the expression of miRNA in the ovaries and testes and associated reproductive functions.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant found widely across the world. While animal and human studies have shown that exposure to TCDD may cause significant alterations in the reproductive tract, the effect of TCDD on the expression of miRNA in the reproductive organs has not been previously tested. In the current study, we exposed adult female or male mice to TCDD or vehicle and bred them to study the impact on reproduction. The data showed that while TCDD treatment of females caused no significant change in litter size, it did alter the survival of the pups. Also, TCDD exposure of either the male or female mice led to an increase in the gestational period. While TCDD did not alter the gross morphology of the ovaries and testes, it induced significant alterations in the miRNA expression. The ovaries showed the differential expression of 426 miRNAs, of which 315 miRNAs were upregulated and 111 miRNA that were downregulated after TCDD exposure when compared to the vehicle controls. In the testes, TCDD caused the differential expression of 433 miRNAs, with 247 miRNAs upregulated and 186 miRNAs downregulated. Pathway analysis showed that several of these dysregulated miRNAs targeted reproductive functions. The current study suggests that the reproductive toxicity of TCDD may result from alterations in the miRNA expression in the reproductive organs. Because miRNAs also represent one of the epigenetic pathways of gene expression, our studies suggest that the transgenerational toxicity of TCDD may also result from dysregulation in the miRNAs.


Biocompatibility evaluation of antibacterial Ti-Ag alloys with nanotubular coatings.
Implant-related infection is a major problem postsurgery. As an alternative to a localized antibiotic release system, we used Ag to fabricate Ti-Ag alloys with nanotubular coatings (TiAg-NTs). Ag has excellent antibacterial properties, but its biological toxicity is a concern. Therefore, we performed biological experiments both in vitro and in vivo to evaluate the biocompatibility of TiAg-NTs with different concentrations of Ag (1%, 2%, and 4%). For in vitro experiments, cytocompatibility, including cell attachment, viability, and proliferation, was tested, and genes and proteins related to osteogenic differentiation were also evaluated. For in vivo assays, the rat femoral condylar insertion model was used, and micro-computed tomography (micro-CT) and histological analysis were conducted to analyze bone formation around implants at 1, 2, and 4 weeks after surgery. Both in vitro and in vivo results indicate that Ti2%Ag-NT showed comparable cytocompatibility with commercially pure Ti (cp-Ti), and it could achieve good osseointegration with the surrounding bone tissue. We thus believe that Ti2%Ag-NT is a potential biomaterial for orthopedics.


Green micellar HPLC analysis of three angiotensin-converting enzyme inhibitors in their mixtures with hydrochlorothiazide and modeling of their retention behavior by fitting to Foley's model.
We present an environmentally friendly method for the analysis of three angiotensin-converting enzyme inhibitors and hydrochlorothiazide simultaneously using a green micellar eluent for the first time. The chromatographic separation of enalapril maleate, lisinopril dihydrate, benazepril hydrochloride, and hydrochlorothiazide was implemented on an octadecyl silica column with a solution containing sodium dodecyl sulfate (0.12 M), 1-propyl alcohol (10% v/v), triethylamine (0.3% v/v), and H3 PO4 (0.02 M) at pH 3.6 as the mobile phase and UV detection at 210 nm. Validity of the method was confirmed and it exhibited good linearity within the ranges of 5.0-50.0 μg/mL for hydrochlorothiazide and 10.0-60.0 μg/mL for the three angiotensin-converting enzyme inhibitors with a limit of detection of 0.39 to 1.15 μg/mL for all the studied drugs. The developed micellar high-performance liquid chromatography method enables the quantification of the targeted angiotensin-converting enzyme inhibitors in combined tablets with hydrochlorothiazide by isocratic elution. There is no need for special precautions to prevent broadening and splitting of their chromatographic peaks. The method fulfills the society rights for safe and green analytical methods. The retention behavior of the four studied drugs was fitted to Foley's model and their association equilibria to the micelles (KAM ) and to the surface-modified stationary phase (KAS ) were calculated.


Implementation of the European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA) sedation training course in a regular endoscopy unit.
Several scientific societies have endorsed non-anesthesiologist sedation (NAS) during gastrointestinal endoscopy, considering it a safe procedure when administered by adequately trained personnel. This study aimed to evaluate the occurrence of adverse events after implementation of the European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA) sedation training program. From January 2017 to August 2018, data from all consecutive endoscopic procedures in adults (≥ 18 years) performed at our endoscopy unit were collected using an electronic reporting system. All staff (physicians and nurses) completed the ESGE-ESGENA sedation course. In total, 12 132 patients underwent endoscopic procedures, 10 755 (88.6 %) of which were performed in a non-anesthesiological setting. Of these, about 20 % used moderate sedation with midazolam + fentanyl and 80 % used deep sedation with additional propofol. No sentinel, 5 (0.05 %) moderate risk, and 18 (0.17 %) minor risk adverse events occurred, all during moderate or deep sedation, and all managed by endoscopy staff without the need for anesthesiologist assistance. After completing the ESGE-ESGENA sedation training program, the rate of adverse events was very low in our institution. The findings support implementation of the program in all digestive endoscopy units and inclusion in the curriculum for physicians and nurses to ensure safe endoscopic procedures.


Patterns of colonisation and the "thrifty" genotype in Pacific prehistory.
The seemingly distinctive markers of Polynesian biology - serologic, molecular, anatomical, and developmental - have been argued to have emerged from the special circumstances of colonisation and early settlement of the region. Models point to the microevolutionary impact of mortality selection while voyaging, small founding group size forcing bottlenecking, and subsequent relative isolation of groups introducing heterogeneity through genetic drift within Polynesia. These ideas have drawn on a melange of ideas about the colonising experience to construct evolutionary narratives, including that of the "thrifty" genotype in Polynesia. The substantial problem is that there previously has been no independent theory of colonisation and inter-island contact for the region. We critically examine which microevolutionary forces would have impacted prehistoric Polynesians in terms of an independent navigational theory of colonisation, and map out the expected biological/ evolutionary sequelae. This theory suggests that Remote Oceania was settled by directed return voyages, that the tempo of population expansion was probably rapid, that voyaging continued after settlement, that whereas episodes of colonisation were directed to safety, subsequent inter-group voyages followed the pattern of mutual inter-island accessibility. The implication is that mortality selection would not have been the predominant force shaping the Polynesian genotype; the development of survival sailing strategies were designed to remove these very risks. This makes it unlikely that the specific experience of Polynesian colonisation would promote an efficient insulin mechanism, and so explain, for example, the high incidence of Type II diabetes mellitus in contemporary Polynesian groups.


Containment of polioviruses after eradication and OPV cessation: characterizing risks to improve management.
The goal of the World Health Organization is to stop routine use of oral poliovirus vaccine shortly after interruption of wild poliovirus transmission. A key component of this goal is to minimize the risk of reintroduction by destruction of polioviruses except in an absolute minimum number of facilities that serve essential functions and implement effective containment. Effective containment begins with a complete facility risk assessment. This article focuses on characterizing the risks of exposure to polioviruses from the essential vaccine production, quality control, and international reference and research facilities that remain. We consider the potential exposure pathways that might lead to a poliovirus reintroduction, including para-occupational exposures and releases to the environment, and review the literature to provide available estimates and a qualitative assessment of containment risks. Minimizing the risk of poliovirus transmission from a poliovirus facility to increasingly susceptible communities is a crucial and ongoing effort requiring understanding and actively managing the potential exposure pathways.


Sonography for diagnosis of cervical ribs in children.
The purpose of this series was to describe the use of sonography for diagnosis of cervical ribs in children. Two children had hard nonmobile supraclavicular masses that were of clinical concern for malignancy. Both children were first evaluated by sonography. Sonography showed each mass to be a tubular bony structure with a cartilaginous end. They were thought to represent cervical ribs. This anatomic variant was subsequently confirmed with radiography in 1 case and computed tomography in the other. Musculoskeletal sonography may offer a reliable method for diagnosing cervical ribs without the need for ionizing radiation.


Effect of Exercise on Brain-Derived Neurotrophic Factor in Stroke Survivors: A Systematic Review and Meta-Analysis.
BDNF (brain-derived neurotrophic factor) is a biomarker of neuroplasticity linked with better functional outcomes after stroke. Early evidence suggests that increased concentrations after exercise may be possible for people with stroke, however it is unclear how exercise parameters influence BDNF concentration. This systematic review and meta-analysis searched 7 electronic databases. Experimental or observational studies measuring changes in BDNF concentration after exercise in people poststroke were included. Data were extracted including characteristics of the study, participants, interventions, and outcomes. Several fixed and random effects meta-analyses were completed. Seventeen studies including a total of 687 participants met the eligibility criteria (6 randomized trials). Significant improvements were observed in BDNF concentration following a single session (mean difference, 2.49 ng/mL; [95% CI, 1.10-3.88]) and program of high intensity aerobic exercise (mean difference, 3.42 ng/mL; [95% CI, 1.92-4.92]). High intensity aerobic exercise can increase circulating BDNF concentrations, which may contribute to increased neuroplasticity. URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42021251083.


Challenges in therapy of hypertension in the elderly.
Treating older hypertensive patients presents special challenges. The physiological effects of aging result in hemodynamic and pharmacokinetic changes. Geriatric patients are more likely to have concomitant diseases than younger patients. Treatment regimens should be individualized; monotherapy should be the goal. While most antihypertensive agents can be used, each class of drugs has advantages and disadvantages. Diuretics are both effective and inexpensive but their metabolic side effects (especially hypokalemia) may be quite serious in the geriatric population. Sympatholytics, beta-blockers, alpha-blockers, and direct vasodilators may not be tolerated. The angiotension-converting enzyme inhibitors, captopril and enalapril, are good choices because they have favorable hemodynamics, renin and nonrenin-dependent mechanisms of action and are associated with minimal biochemical alterations. In a recent multicenter study, captopril (25 mg twice daily) was given to 99 geriatric patients with seated diastolic blood pressure (BP) of 92-110 mm Hg. Patients whose blood pressures were not controlled after two weeks of therapy were randomized to either Capozide (captopril, 25 mg with 15 mg hydrochlorothiazide) or captopril, 50 mg twice daily. The average decrease in BP was 16.9/11.9 mm Hg; 75.8% of patients responded to treatment. Black and white patients had equal responses. Only five patients withdrew from the study due to adverse reactions, none of which was serious. Geriatric hypertensives should be treated. Because captopril and Capozide are well-tolerated, effective medications in elderly patients with mild, moderate, or severe hypertension, they should be considered as initial therapy for geriatric hypertension.


Current Trends about Inner Limiting Membrane Peeling in Surgery for Epiretinal Membranes.
The inner limiting membrane (ILM) is the basement membrane of the Müller cells and can act as a scaffold for cellular proliferation in the pathophysiology of disorders affecting the vitreomacular interface. The atraumatic removal of the macular ILM has been proposed for treating various forms of tractional maculopathy in particular for macular pucker. In the last decade, the removal of ILM has become a routine practice in the surgery of the epiretinal membranes (ERMs), with good anatomical results. However many recent studies showed that ILM peeling is a procedure that can cause immediate traumatic effects and progressive modification on the underlying inner retinal layers. Moreover, it is unclear whether ILM peeling is helpful to improve vision after surgery for ERM. In this review, we describe the current understanding about ILM peeling and highlight the beneficial and adverse effects associated with this surgical procedure.


Leptin secretion from adipose tissue in women. Relationship to plasma levels and gene expression.
The role of expression and secretion of the ob gene product, leptin, for the regulation of plasma leptin levels has been investigated in vitro using abdominal subcutaneous adipose tissue of 20 obese, otherwise healthy, and 11 nonobese women. Body mass index (BMI, mean+/-SEM; kg/m2) in the two groups was 41+/-2 and 23+/-1, respectively. Fat cell volume was 815+/-55 pl in the obese and 320+/-46 pl in the nonobese group. In the obese group, plasma leptin concentrations and adipose leptin mRNA (relative to gamma actin) were increased five and two times, respectively. Moreover, adipose tissue secretion rates per gram lipid weight or per fat cell number were also increased two and seven times, respectively, in the obese group. There were strong linear correlations (r = 0.6-0.8) between plasma leptin, leptin secretion, and leptin mRNA. All of these leptin measurements correlated strongly with BMI and fat cell volume (r = 0.7- 0.9). About 60% of the variation in plasma leptin could be attributed to variations in leptin secretion rate, BMI, or fat cell volume. We conclude that elevated circulating levels of leptin in obese women above all result from accelerated secretion rates of the peptide from adipose tissue because of increased ob gene expression. However, leptin mRNA, leptin secretion, and circulating leptin levels are all more closely related to the stored amount of lipids in the fat cells of adipose tissue than they are to an arbitrary division into obese versus nonobese.


Phospholipids in milk fat: composition, biological and technological significance, and analytical strategies.
Glycerophospholipids and sphingolipids are quantitatively the most important phospholipids (PLs) in milk. They are located on the milk fat globule membrane (MFGM) and in other membranous material of the skim milk phase. They include principally phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and phosphatidylserine, while sphingomyelin is the dominant species of sphingolipids There is considerable evidence that PLs have beneficial health effects, such as regulation of the inflammatory reactions, chemopreventive and chemotherapeutic activity on some types of cancer, and inhibition of the cholesterol absorption. PLs show good emulsifying properties and can be used as a delivery system for liposoluble constituents. Due to the amphiphilic characteristics of these molecules, their extraction, separation and detection are critical points in the analytical approach. The extraction by using chloroform and methanol, followed by the determination by high pressure liquid chromatography (HPLC), coupled with evaporative light scattering (ELSD) or mass detector (MS), are the most applied procedures for the PL evaluation. More recently, nuclear magnetic resonance spectrometry (NMR) was also used, but despite it demonstrating high sensitivity, it requires more studies to obtain accurate results. This review is focused on milk fat phospholipids; their composition, biological activity, technological properties, and significance in the structure of milk fat. Different analytical methodologies are also discussed.


Characteristics of extracellular polymeric substances and soluble microbial products of activated sludge in a pulse aerated reactor.
This study aimed to investigate the stratification characteristics of extracellular polymeric substances (EPS) and the properties of soluble microbial products (SMP) of the activated sludge with pulse aeration. The activated sludge was acclimated with aeration on/off time of 5 min/10 min for 60 days. The results showed that both polysaccharides (PS) and proteins (PN) increased in the loosely bound EPS (LB-EPS) and the tightly bound EPS (TB-EPS) with the increase of operational time. Both the PN/PS ratio and the total LB-EPS increased in the later period of the pulse aerated acclimation process. There was an obvious positive correlation between sludge volume index (SVI) and LB-EPS (R 2 = 0.871), mainly due to the PS in LB-EPS which was also significantly correlated with SVI (R 2 = 0.954). A downward trend of SMP concentrations occurred at the end of acclimation which was opposite to the upward change of EPS contents. Two obvious fluorescence peaks were detected respectively in EPS and SMP by 3D-EEM fluorescence spectroscopy. Peak A was detected in both LB-EPS and TB-EPS, which was associated with tryptophan protein-like substances. Peak B representing humus carbon and carboxylic acids was mainly detected in SMP. The release of humus-like components in SMP from activated sludge was mainly in accordance with the dissolution and hydrolysis of PN in TB-EPS.


[The outbreak of an epidemic of tick-borne encephalitis in Kielec province induced by milk ingestion].
Outbreak of tick-borne encephalitis (TBE) was reported between May 14 and June 20 1995 in Busko Zdrój in Kielce Province. Drinking fresh (unboiled) goat's milk from private breeding was probable reason of the outbreak. 63 person drank goat's milk from the same source; 15 were hospitalized with neurological symptoms, 33 persons had an influenza-like symptoms and were treated in out-patient department (27) or healed spontaneously (6), and 15 persons were healthy. TBE virus antibodies were found in CSF of all 15 persons with neuroinfection syndromes. IgM and IgG against TBE virus were present in sera of 15 hospitalized patients and 20 patients with influenza like-syndromes. Antibodies to TBE virus were detected in serum of one of 19 goats from the breeding farm confirming the source of TBE virus infection.


Pleural metastatic tumours and effusions. Frequency and pathogenic mechanisms in a post-mortem series.
We examined the post-mortem records of 191 patients who had one or more malignant tumours (196 neoplasms in total). We found 55 cases with pleural metastases (28%) and 30 of these presented pleural effusions (15% of the total number of neoplasms). The visceral pleural was involved in all 24 cases of lung cancer with pleural metastasis and in 27 out of 31 of those of other origins. The parietal pleura was affected in 16 out of 24 cases of the lung tumours and in 15 out of 31 of those of other origins. There were no cases in which only the parietal layer of the pleura was involved, with the only exception of neighbouring tumours. We found neoplastic vascular invasion in 43 out of 55 cases, retrograde lymphatic spread from the mediastinum in two cases, and direct pleural involvement from a neighbouring tumour in the remaining. We conclude that malignant pleural implantation fundamentally arises from the spread of tumour emboli to the lungs and the visceral pleura, with secondary seedings to the parietal pleura. Therefore, this phenomenon leads to the usual finding of lower involvement of parietal pleura as compared to the visceral pleura in our series.


Photoinduced Generation of a Durable Thermal Proton Reduction Catalyst with in Situ Conversion of Mn(bpy)(CO)3Br to Mn(bpy)2Br2.
The conversion of protons to H2 is a critical reaction for the design of renewable fuel generating systems. Robust, earth-abundant, metal-based catalysts that can rapidly facilitate this reduction reaction are highly desirable. Mn(bpy)(CO)3Br generates an active catalyst for the proton reduction reaction upon photolysis at a high, directly observed H2 production rate of 1 300 000 turnovers per hour, with a low driving force for this reaction. Through the use of FcMe10 as an electron source, a proton source (triflic acid, 4-cyanoanilinium, or tosylic acid), and MeCN/H2O as solvent, the thermal reaction at room temperature was found to proceed until complete consumption of the electron source. No apparent loss in catalytic activity was observed to the probed limit of 10 000 000 turnovers of H2. Interestingly, a catalytically competent complex (Mn(bpy)2Br2), which could be isolated and characterized, formed upon photolysis of Mn(bpy)(CO)3Br in the presence of acid.


Safety and efficacy of left colic artery preservation in laparoscopic anterior resection for lower rectal cancer.
Background: To evaluate the safety and efficacy of left colic artery (LCA) preservation in laparoscopic anterior resection with D3 lymphadenectomy for lower rectal cancer. Methods: A total of 117 patients with lower rectal cancer who received laparoscopic anterior resection were retrospectively analyzed. Results: No differences were detected in terms of the numbers of harvested lymph nodes and metastatic lymph nodes, the intraoperative and postoperative complications or the postoperative recurrence and survival rates between the two groups (p > 0.05), but the LCA preservation group showed a lower anastomotic leakage rate than the LCA nonpreservation group (2/49 vs 12/68). Conclusion: LCA preservation may help reduce the incidence of anastomotic leakage without impairing surgical and oncological outcomes.


Diversity and Effect of Increasing Temperature on the Activity of Methanotrophs in Sediments of Fildes Peninsula Freshwater Lakes, King George Island, Antarctica.
Global warming has a strong impact on polar regions. Particularly, the Antarctic Peninsula and nearby islands have experienced a marked warming trend in the past 50 years. Therefore, higher methane (CH4) emissions from this area could be expected in the future. Since mitigation of these emissions can be carried out by microbial oxidation, understanding this biological process is crucial since to our knowledge, no related studies have been performed in this area before. In this work, the aerobic CH4 oxidation potential of five freshwater lake sediments of Fildes Peninsula (King George Island, South Shetland Islands) was determined with values from 0.07 to 10 μmol CH4 gdw-1 day-1 and revealed up to 100-fold increase in temperature gradients (5, 10, 15, and 20°C). The structure and diversity of the bacterial community in the sediments were analyzed by next-generation sequencing (Illumina MiSeq) of 16S rRNA and pmoA genes. A total of 4,836 ASVs were identified being Proteobacteria, Actinobacteriota, Acidobacteriota, and Bacteroidota the most abundant phyla. The analysis of the pmoA gene identified 200 ASVs of methanotrophs, being Methylobacter Clade 2 (Type I, family Methylococcaceae) the main responsible of the aerobic CH4 oxidation. Moreover, both approaches revealed the presence of methanotrophs of the classes Gammaproteobacteria (families Methylococcaceae and Crenotrichaceae), Alphaproteobacteria (family Methylocystaceae), Verrucomicrobia (family Methylacidiphilaceae), and the candidate phylum of anaerobic methanotrophs Methylomirabilota. In addition, bacterial phospholipid fatty acids (PLFA) biomarkers were studied as a proxy for aerobic methane-oxidizing bacteria and confirmed these results. Methanotrophic bacterial diversity was significantly correlated with pH. In conclusion, our findings suggest that aerobic methanotrophs could mitigate in situ CH4 emissions in a future scenario with higher temperatures in this climate-sensitive area. This study provides new insights into the diversity of methanotrophs, as well as the influence of temperature on the CH4 oxidation potential in sediments of freshwater lakes in polar regions of the southern hemisphere.


Clethramycin, a new inhibitor of pollen tube growth with antifungal activity from Streptomyces hygroscopicus TP-A0623. I. Screening, taxonomy, fermentation, isolation and biological properties.
The cytoskeletal proteins, actin and myosin, play a central role in pollen tube growth. The pollen tube growth is inhibited by cytochalasin, which interferes with actin polymerization. In the screening of pollen tube growth inhibitors, clethramycin was found from the fermentation broth of an actinomycete strain TP-A0623. The producing strain was isolated from a root of Clethra barbinervis collected in Toyama, Japan and identified as Streptomyces hygroscopicus based on the taxonomic study. Clethramycin showed in vitro antifungal activity against yeast such as Candida albicans and C. glabrata with the MIC of 0.5 approximately 8 microg/ml, but weak activity against Gram-positive and negative bacteria (MIC > or = 64 microg/ml). Cytotoxicity of clethramycin was moderate and the IC50 was 57 microg/ml against HeLa cells and 120 microg/ml against WI-38 cells.


A feasibility study of a randomised controlled trial to examine the impact of the ABCDE bundle on quality of life in ICU survivors.
Early rehabilitation has been found to prevent delirium and weakness that can hamper the recovery of intensive care unit (ICU) survivors. Integrated clinical practice guidelines for managing patient pain, agitation and delirium (PAD) have been developed. The Awakening and Breathing Coordination, Delirium monitoring/management, and Early exercise/mobility (ABCDE) bundle provides a strategy to implement PAD guidelines into everyday clinical practice. However, there is limited evidence on the effectiveness of the ABCDE bundle in the literature.The purpose of this study was to evaluate the feasibility of conducting a full-scale randomised controlled trial comparing the ABCDE bundle to standard care in an ICU. Trial feasibility was defined as the successful recruitment and retention of trial participants, adherence to the intervention, identification of barriers to the intervention, and the rigorous collection of outcome data. A prospective, single-centre, randomised controlled feasibility study was conducted. Thirty adult mechanically ventilated participants were recruited from an eight-bed ICU in south east Queensland, Australia, between April 2015 and December 2015. Participants were randomised to receive either the ABCDE bundle or standard routine management. The ABCDE bundle integrated prescribed awakening and breathing trials, delirium monitoring and management, and prescribed exercise and mobility regimes. Feasibility outcomes measured included recruitment and retention rates, intervention fidelity, and the feasibility of participant outcome data collection. Outcome measurement assessors were blinded to participant assignment. It was not possible to blind the research team or the participant to group assignment. In total, 30 (81.1%) of 37 eligible participants consented and were randomised to the intervention group (n = 15) or the control group (n = 15). Of these, 23 (76.6%) participants successfully completed the 90-day post discharge assessment. A lengthy recruitment period of 8 months was related to overly stringent inclusion and exclusion criteria. Intervention adherence exceeded defined success rates with participation in awakening and breathing trials, delirium monitoring and exercise interventions performed on 80.2, 97.4 and 90.2% of ventilated days respectively. Outcome assessments were successfully and accurately performed at ICU and hospital discharge and 90-day post hospital discharge. Intervention participants were deemed to be delirious on 39.6% of mechanically ventilated days indicating a requirement for a scripted regime to prevent delirium. With minor adjustment of inclusion and exclusion criteria, the inclusion of delirium management protocols, and encouragement of family engagement and involvement, a large-scale definitive randomised controlled trial to test the impact of the ABCDEF bundle will be feasible. Australian New Zealand Clinical Trials Registry 12614000763640 Date registered 17/08/2014.


Delivering the Acetylcholine Neurotransmitter by Nanodrugs as an Effective Treatment for Alzheimer's Disease.
The current clinical symptomatic therapy for Alzheimer's disease involves increasing acetylcholine levels in the brain by inhibiting acetylcholinesterase. However, the effectiveness of acetylcholinesterase inhibitors decreases as the disease progresses, leading to many side effects including over-inhibition of other enzymes and hepatic injury. Herein, we investigate the effects of the direct delivery of a low-dose of acetylcholine via human serum albumin nanoparticles to brain. This novel nanodrug improved both spatial learning and memory capability, whereas it reduced oxidative damage in mice. More importantly, damage to the liver or interference with the inherent neurotransmitter generation due to supplementation were almost absent. Our study is the first to demonstrate that supplementation of acetylcholine-loaded nanoparticles might offer a better therapeutic option in the ease of Alzheimer's disease.


HSP90 inhibition downregulates thymidylate synthase and sensitizes colorectal cancer cell lines to the effect of 5FU-based chemotherapy.
Cell cycle progression and DNA synthesis are essential steps in cancer cell growth. Thymidylate synthase (TS) is a therapeutic target for 5FU. We tested the hypothesis that HSP90 transcriptional and functional inhibition can inhibit cell cycle progression, downregulate TS levels and sensitize colorectal cancer (CRC) cell lines to the effects of 5FU. Treatment with ganetespib (50 nM) for 24 hours inhibited cyclin D1 and pRb at the transcriptional and translational levels and induced p21, leading to G0/G1 cell cycle arrest in both CRC cell lines (HCT-116 and HT-29). This was associated with downregulation of E2F1 and its target gene TS. In addition, ganetespib inhibited PI3K/Akt and ERK signalling pathways. Similar effects were observed with HSP90 knockdown in both cell lines. Ganetespib sensitized CRC cell lines to the effects of oxaliplatin and 5FU. Similar effects were also observed in tumors from animals treated with ganetespib, oxaliplatin and 5FU. In this study, we present in vitro and animal data supporting that the targeting of HSP90 decreases CRC cell survival and proliferation. Ganetespib sensitizes CRC cell lines to the effects of 5FU-based chemotherapy. Combining HSP90 inhibitors with chemotherapy is a rational approach for future drug development in CRC.


Association of cyclophilins and cardiovascular risk factors in coronary artery disease.
Cyclophilins are chaperone proteins that play important roles in signal transduction. Among them, cyclophilins A, B, C, and D were widely associated with inflammation and cardiovascular diseases. Cyclophilins A and C have been proposed as coronary artery disease biomarkers. However, less is known about their relationship with cardiovascular risk factors. Therefore, this study aimed to determine the association between cyclophilin A, B, C, and D and cardiovascular risk factors in coronary artery disease. Serum levels of cyclophilins were measured in 167 subjects (subdivided according to cardiovascular risk factors presence). This study reveals that cyclophilin A and C are elevated in patients regardless of the risk factors presence. Moreover, cyclophilin B is elevated in male patients with hypertension, type 2 diabetes, or high glucose levels. In addition, cyclophilins A, B, and C were significantly correlated with cardiovascular risk factors, but only cyclophilin B was associated with type 2 diabetes. The multivariate analysis strengthens the predictive value for coronary artery disease presence of cyclophilin A (>8.2 ng/mL) and cyclophilin C (>17.5 pg/mL) along with the cardiovascular risk factors tobacco, hypertension, dyslipidemia, and high glucose and cholesterol levels. Moreover, the risk of coronary artery disease is increased in presence of cyclophilin B levels above 63.26 pg/mL and with hypertension or dyslipidemia in male patients. Consequently, cyclophilins A and C serum levels are reinforced as useful coronary artery disease biomarkers, meanwhile, cyclophilin B is a valuable biomarker in the male population when patients are also suffering from hypertension or dyslipidemia.


Relative bioavailability of rapidly dispersing, plain, and microencapsuled acetylsalicylic acid tablets after single dose administration.
Extent and rate of absorption of acetylsalicylic acid (ASA) from rapidly dispersing (Acesal Extra) and plain tablets (Acesal) relative to reference 1 (plain tablets, Aspirin) and from microcapsuled tablets (Micristin) relative to comparable listed tablets (reference 2, Colfarit) were assessed in 2 single-dose (0.5 g ASA), open, randomized, crossover studies with intervals of 14 days between 2 periods. Both studies were performed in 24 male and female healthy volunteers each (age 18-32 years, body weight 48-90 kg, body height 161-190 cm). ASA and its metabolite salicylic acid (SA) were measured with an HPLC method validated for ASA between 0.2 and 20 microg/ml and for SA between 0.4 and 40 microg/ml. The test tablets were considered bioequivalent with reference in extent of absorption if the 90% confidence limits of the AUC0 to infinity ratio were within the range of 0.80-1.25, and in rate of absorption if the confidence limits of the Cmax/AUC0 to infinity ratios were within 0.70-1.43. Geometric means and 90% confidence limits for the test/reference ratios of the comparisons Acesal vs reference 1, Acesal Extra vs reference 1 and Micristin vs reference 2 were 1.05 (0.97-1.13), 1.13 (1.05-1.22), 1.02 (0.92-1.14) for ASA AUC0 to infinity and 1.02 (0.96-1.07), 1.05 (0.99-1.11), 0.98 (0.91-1.04) for SA AUC0 to infinity, respectively. The results for Cmax/AUC of ASA were 1.16 (1.00-1.34), 1.72 (1.49-1.99), 0.83 (0.73-0.94) and of SA 1.02 (0.98-1.07), 1.07 (1.02-1.12), 0.93 (0.88-0.97). Acesal and Micristin were bioequivalent with the respective references in both extent and rate of absorption. Acesal Extra and reference 1 were bioequivalent with regard to extent only. Acesal Extra was absorbed faster.


Comparative Analysis Based on Physiological and Transcriptomic Data between Juvenile and Adult Tree Peony (Paeonia delavayi).
A long juvenile period limits the breeding process of many woody plants including tree peony. To investigate the physiological and transcriptomic differences between juvenile and adult plants of tree peony and to explore the key SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) genes, which are vital in age-dependent pathways, 1-year-old and 3-year-old Paeonia delavayi plants were used to compare the relevant physiological parameters and transcriptomic profiles of the leaves in two phases of plants. The results of the physiological parameters showed that the starch content in the leaves of adult plants remained unchanged and that the soluble sugar content significantly increased compared with those in the juvenile plants. In terms of plant hormones, the contents of cytokinin-like hormone (N6-isopentenyladenine (iP)) and jasmonic acid (JA) significantly decreased, whereas the contents of auxin (indole-3-acetic acid, IAA), abscisic acid (ABA), cytokinin-like hormone (N6-isopentenyladenenosine (iPR)), and ethylene precursor (1-aminocyclopropane-1-carboxylic acid, ACC) showed no statistic difference. Transcriptome sequencing results showed that there were 194 differentially expressed genes (DEGs) between juvenile and adult plants, including 171 up-regulated DEGs and 23 down-regulated DEGs. Circadian rhythm, plant hormone signal transduction, and sugar metabolism were closely related to the juvenile-to-adult transition in P. delavayi, involving a total of 12 DEGs. In addition, a total of 13 SPL genes were identified in the transcriptome data, but only PdSPL10 (c71307.graph_c0) was differentially expressed. It was further validated via qRT-PCR analysis, indicating that PdSPL10 might be a key gene regulating the process of juvenile-to-adult in P. delavayi. Based on the above results, a hypothetical transcriptional network regulating juvenile-to-adult transition and flowering in P. delavayi was proposed. These findings provide a reference for understanding the mechanism of juvenile-to-adult transition in tree peony.


An unusual case of gastrointestinal mucormycosis in a patient with nephrotic syndrome.
Immunosuppression predisposes to a variety of infections, some of which occur at unusual sites. Of all the forms of mucormycosis, involvement of the intestines is rare. High degree of suspicion along with the use of invasive procedures can facilitate the diagnosis of these infections. We report a rare case of gastrointestinal Mucor in a patient with nephrotic syndrome.


The extended growth of graphene oxide flakes using ethanol CVD.
We report the extended growth of Graphene Oxide (GO) flakes using atmospheric pressure ethanol Chemical Vapor Deposition (CVD). GO was used to catalyze the deposition of carbon on a substrate in the ethanol CVD with Ar and H2 as carrier gases. Raman, SEM, XPS and AFM characterized the growth to be a reduced GO (RGO) of <5 layers. This newly grown RGO possesses lower defect density with larger and increased distribution of sp(2) domains than chemically reduced RGO. Furthermore this method without optimization reduces the relative standard deviation of electrical conductivity between chips, from 80.5% to 16.5%, enabling RGO to be used in practical electronic devices.


Meniscal injury: II. Management.
Meniscal repair is a viable alternative to resection in many clinical situations. Repair techniques traditionally have utilized a variety of suture methods, including inside-out and outside-in techniques. Bioabsorbable implants permit all-inside arthroscopic repairs. The success of meniscal repair depends on appropriate meniscal bed preparation and surgical technique and is also influenced by biologic factors such as tear rim width and associated ligamentous injury. Successful repair in >80% of cases has been reported in conjunction with anterior cruciate ligament reconstruction. Success rates are lower for isolated repairs. Complications related to repair include neurologic injury, postoperative loss of motion, recurrence of the tear, and infection. Meniscal allograft transplantation may provide a treatment option when meniscus salvage is not possible or when a previous total meniscectomy has been done.


Ventriculo-peritoneal shunting is a safe and effective treatment for idiopathic intracranial hypertension.
To determine the outcome of ventriculo-peritoneal shunts as a treatment for idiopathic intracranial hypertension (IIH) Materials and Methods: Retrospective case series of 28 patients with IIH and evidence of raised intracranial pressure (ICP) who underwent shunt insertion. Patients were identified from a prospectively updated operative database. A case-notes review was performed and data on type of shunt, pre- and post-operative symptoms, ophthalmological findings and post-operative complications were recorded. All patients had symptoms of IIH that had failed medical management. Twelve patients had previous lumbo-peritoneal shunts and 2 patients had previous venous sinus stents. All patients had evidence of raised ICP as papilloedema and raised CSF pressure on lumbar puncture. Twenty-seven patients received a ventriculo-peritoneal shunt and 1 patient a ventriculo-atrial shunt. Twenty-six patients received Orbis Sigma Valves and 2 patients Strata valves. At follow-up all patients (100%) had improvement/resolution of papilloedema, 93% had improved visual acuity and 84% had improved headaches. Mean time to last follow-up was 15 (range 4-96) months. Complications occurred in 3 patients (11%): 2 patients required revision of their peritoneal catheters and 1 patient had an anti-siphon device inserted. Previous literature reported a ventricular shunt revision rate of 22-42% in the management of IIH. We demonstrate ventriculo-peritoneal shunts to be an effective treatment with a revision rate of 11% compared to the previously reported 22-42%.


Grey matter involvement by focal cervical spinal cord lesions is associated with progressive multiple sclerosis.
The in vivo relationship of spinal cord lesion features with clinical course and function in multiple sclerosis (MS) is poorly defined. The objective of this paper is to investigate the associations of spinal cord lesion features on MRI with MS subgroup and disability. We recruited 120 people: 25 clinically isolated syndrome, 35 relapsing-remitting (RR), 30 secondary progressive (SP), and 30 primary progressive (PP) MS. Disability was measured using the Expanded Disability Status Scale. We performed 3T axial cervical cord MRI, using 3D-fast-field-echo and phase-sensitive-inversion-recovery sequences. Both focal lesions and diffuse abnormalities were recorded. Focal lesions were classified according to the number of white matter (WM) columns involved and whether they extended to grey matter (GM). The proportion of patients with focal lesions involving at least two WM columns and extending to GM was higher in SPMS than in RRMS (p = 0.03) and PPMS (p = 0.015). Diffuse abnormalities were more common in both PPMS and SPMS, compared with RRMS (OR 6.1 (p = 0.002) and 5.7 (p = 0.003), respectively). The number of lesions per patient involving both the lateral column and extending to GM was independently associated with disability (p < 0.001). More extensive focal cord lesions, extension of lesions to GM, and diffuse abnormalities are associated with progressive MS and disability.


Single-stick tunneled central venous access using the jugular veins in infants weighing less than 5 kg.
Despite the demonstrated feasibility of the single-stick technique in the femoral vein, its use in neonates and infants for placing central lines in internal and external jugular veins has not been reported. Describe and assess the safety and efficacy of tunneled jugular central venous catheter placement performed under ultrasound (US) and fluoroscopic guidance in neonates and infants weighing <5 kg using the single-stick technique at three tertiary pediatric hospitals. Thirty-three children weighing less than 5 kg received tunneled central venous access in either internal or external jugular veins using the single-stick technique. Patient history, procedural records and clinical follow-up documents were retrospectively reviewed. Complication rates were compared to those of 41 patients receiving single-stick femoral central lines. Technical complications occurred during one (3.0%) jugular placement with the patient having a failed right-side attempt with subsequent successful left-side placement. The catheters did not last the entire course of treatment in three (9.1%) patients with jugular lines. One patient had the catheter removed due to concern for infection, one catheter was accidentally removed during dressing changes, and one catheter was displaced and subsequently exchanged. Of patients receiving femoral central lines, 1 (2.4%) had a technical complication and 5 catheters (12.2%) did not last the entire course of treatment. The placement of tunneled central venous catheters in neonates/infants <5 kg is safe and technically feasible using the internal/external jugular vein via the single-stick technique. By theoretically reducing the risks of catheter infection by avoiding the diaper area and thrombosis by using larger veins, it may be preferable in certain patient populations.


Gut microbiota composition after a dietary and physical activity intervention: a pilot study in Mexican children with obesity.
Gut microbiota is a complex organized collection of microorganisms that confers multiple metabolic advantages to the host. The reduced diversity and proportion of specific gut microbial species have been associated with obesity and metabolic disorders. Multidimensional interventions, including modifications in dietary and physical activity habits, are associated with favorable changes in microbiota composition. This pilot study aimed to evaluate changes in the gut microbiota composition of Mexican children with obesity before and after a 6-week multidimensional intervention. Blood and stool samples were collected, and anthropometric measurements were obtained from six children with obesity before and after the intervention. The intervention consisted of modeling a hypo energetic diet and giving nutritional and physical activation recommendations. DNA from stool samples was used to characterize gut microbial composition by sequencing the 16S rRNA gene. The decrease in waist circumference was associated with increased Odoribacter relative abundance. However, gut microbiota composition and diversity remained unchanged. Although no modifications in the body mass index, body fat, composition, or diversity of the gut microbiota were observed with the intervention, it was possible to associate the reduction in waist circumference with the presence of Odoribacter after a multidimensional intervention in Mexican children with obesity.


Isolation of novel bacteria and actinomycetes using soil-extract agar medium.
Novel bacteria were discovered using an isolation technique consisting of (i) selection of microorganisms that grew on soil-extract agar medium, but not on conventional media, and (ii) detection of small microbial colonies with a microscope. Three bacterial strains thus isolated were provisionally designated Shinshu-th1, -th2, -th 3, and five actinomycete strains, Shinshu-MS-01, -02, -03, -04, -05, respectively. Sequence analysis of their 16S rDNA showed that th1 had 95--96% homology with three unculturable bacteria, and th2 had 96% similarity to Bradyrhizobium sp., one unculturable and one unidentified bacterial strain. A phylogenetic study indicated that both strains were alpha-Proteobacteria belonging to the order Rhizobiales and the family Bradyrhizobiaceae. Since they had low homology (96%) with their close relatives, it is possible that th1 and th2 belong to a new genus. The actinomycetes Shinshu-MS-02 and -03 had 95--96% homology with four strains of Actinomadura, -04 had 95--96% similarity to Streptosporangium and Microbispora, and -05 had 97--98% homology with three strains of Acrocarpospora, Herbidospora and Planotetraspora. According to the phylogenetic study, both 02 and 03 are possibly new species of Actinomadura, -04 of Streptosporangium, and -05 of Acrocarpospora. Shinshu-th 3 and -MS-01 were identified as Mycobacterium cookii and Frankia sp., respectively, having 99% homology with these species.


Diagnosis and treatment of paraneoplastic neurological disorders.
In about two thirds of cases, patients with paraneoplastic neurological disorders present to the neurologist without a known tumor. Due to the ongoing immune response, this tumor tends to stay biologically relatively benign, and therefore difficult to diagnose. In patients with a known tumor, the neurological symptoms often precede a tumor recurrence. In both scenarios, anti-neuronal antibodies are an invaluable diagnostic help to the clinician, and may be supplemented by other diagnostic tests such as MRI, CSF, and electrophysiology. Tumor therapy remains the mainstay of therapeutic options, although early immune therapy must be started in parallel. It is hoped that the recent fundamental advances in understanding the autoimmune pathology of these disorders, especially the role of cytotoxic T cells, will eventually lead to more effective treatment options.


Ridge preservation: the new buzzword in dentistry.
The viability of Ridge Preservation as achieved by practicing Advanced Extraction Therapy (AET) and Replacement Therapy (R.T.), will impact the future practice of Dentistry. With the availability of clinically proven materials such as implants (titanium) and synthetic bone substitutes (Bioplant HTR), a practical solution exists to solve a very old clinical problem. Treatment modalities are available today making the atrophic jaw-bone a malady of the past. Imagine no more "dental cripples," and no more inadequate bone situations for implant placements. Ridge Preservation and Replacement Therapy should be practiced regularly: "when we take something out, we should put something back." Our practices will grow. Our patients will thank us.


Corrective outcome and transverse stability after orthognathic surgery using a surgery-first approach in mandibular prognathism with and without facial asymmetry.
The aim of this study was to evaluate corrective outcome and transverse stability after orthognathic surgery via a surgery-first approach (SFA) in mandibular prognathism with and without facial asymmetry using 3-dimensional analysis. Twenty-nine patients who received mandibular setback surgery using SFA were divided into 2 groups according to the menton deviation (4 mm): symmetry group (n = 17) and asymmetry group (n = 12). Using computed tomography images obtained before (T0), immediately after (T1), and 6 months after (T2) surgery, time-dependent changes in variables related to facial asymmetry, including maxillary height, ramal length, frontal and lateral ramal inclination, mandibular body length, and mandibular body height, were evaluated. Immediately after surgery, the asymmetry group showed significantly decreased discrepancies between the longer and non-longer sides for all variables (P < .05); there were no significant differences in discrepancies between the 2 groups. During the postoperative period, no significant changes in discrepancies were found in any variable in either group. Compared with T0, the asymmetry group showed significantly decreased discrepancies in ramal length, frontal and lateral ramal inclination, and mandibular body length at T2. Variables related to facial asymmetry showed significant improvement after surgical-orthodontic treatment using SFA, and corrected outcomes showed good postoperative stability in both the symmetry and asymmetry groups.


NMR investigation of the interaction of vanadate with carbasilatranes in aqueous solutions.
Reaction of vanadate with carbasilatranes [methoxy{N,N',N' '-2,2',3-[bis(1-methylethanolato)(propyl)]amino}silane (1), methoxy{N,N',N' '-2,2',3-[bis(1-ethanolethanolato)(propyl)]amino}silane (2), and {N,N',N' '-2,2',2-[bis(ethanolato)(glycolpropyl ether)]amino}silane (3)] in aqueous solution results in the formation of vanadosilicates and five-coordinated chelate vanadium(V) complexes as evidenced by 51V, 1H, and 13C NMR spectroscopy. Chiral carbasilatrane S,S-1 was characterized in the solid state by X-ray diffraction, revealing a trigonal bipyramidal geometry around the metal ion, with one unidentate methoxy group and one atrane nitrogen atom at the axial positions and one carbon and two atrane oxygen atoms at the equatorial plane of the bipyramid. Crystal data (Mo Kalpha; 100(2) K) are as follows: orthorhombic space group P2(1)2(1)2(1); a = 8.8751(6), b = 9.7031(7), c = 14.2263(12) A; Z = 4. The complexation of vanadium either with 1 or 2 is stereoselective yielding approximately 94% of the complex containing ligand in the S,R-configuration. The lower ability of the S,S- and R,R-diastereoisomers of 1 and 2 to ligate vanadate was attributed to stereochemical factors, dictating a square pyramidal geometry for the chelated complexes. A dynamic process between the vanadium chelate complexes and the respective carbasilatranes was evaluated by 2D {1H} EXSY NMR spectroscopy. These spectra show that the vanadate complexes with the open carbasilatranes exchange more slowly with the free ligand compared to the respective alcohol aminate complexes.


Microfluidic converging/diverging channels optimised for homogeneous extensional deformation.
In this work, we optimise microfluidic converging/diverging geometries in order to produce constant strain-rates along the centreline of the flow, for performing studies under homogeneous extension. The design is examined for both two-dimensional and three-dimensional flows where the effects of aspect ratio and dimensionless contraction length are investigated. Initially, pressure driven flows of Newtonian fluids under creeping flow conditions are considered, which is a reasonable approximation in microfluidics, and the limits of the applicability of the design in terms of Reynolds numbers are investigated. The optimised geometry is then used for studying the flow of viscoelastic fluids and the practical limitations in terms of Weissenberg number are reported. Furthermore, the optimisation strategy is also applied for electro-osmotic driven flows, where the development of a plug-like velocity profile allows for a wider region of homogeneous extensional deformation in the flow field.


Effects of dietary inclusion of yerba mate (Ilex paraguariensis) extract on lamb muscle metabolomics and physicochemical properties in meat.
This study aimed to evaluate the effect of dietary yerba mate (Ilex paraguariensis) extract (YME) on muscle metabolomics and physicochemical properties of lamb meat. Thirty-six uncastrated male lambs (90 d old) were fed experimental diets, which treatments consisted of 0%, 1%, 2%, and 4% inclusion of YME. Animals were fed for 50 d before slaughter. Muscle and meat samples were collected for metabolomics and meat quality analysis, respectively. The experiment was carried out in a randomized block design and analyzed using orthogonal contrasts. There was a quadratic effect of YME inclusion in tenderness (P < 0.05) and a positive linear effect on meat lightness (P < 0.05). No qualitative changes (P > 0.05) on individual metabolites were observed; however, changes in the quantitative metabolic profile were observed, showing that animals fed 1% and 2% of YME have a greater concentration of desirable endogenous muscle antioxidants, with direct impact on metabolic pathways related to beta-alanine metabolism and glutathione metabolism. Therefore, YME dietary supplementation up to 2% of the diet to lambs had little to no effects on the majority of meat quality traits evaluated; moreover, 4% of YME inclusion negatively affected feed intake and meat quality traits.


Quantitative analysis of acetaminophen and its six metabolites in rat plasma using liquid chromatography/tandem mass spectrometry.
Acetaminophen (APAP) is a widely used analgesic and antipyretic drug. It is mainly metabolized by phase 1 and 2 reactions in the liver, and thus it could be involved in many drug-drug interactions. Therefore, the study of APAP metabolism is important in toxicological and pharmacokinetic studies. The objective of this study was to develop a rapid and sensitive method for the determination of APAP and its six metabolites in rat plasma for the pharmacokinetic studies. APAP and its metabolites were separated through a Capcell Pak MGII C(18) column and quantitated with a 16 min run in a triple-quadruple mass spectrometer. The mobile phases were composed of 0.1% formic acid in either 95% water or 95% acetonitrile and analysis was performed twice in positive and negative modes. Validations such as accuracy, precision, recovery, matrix effect and stability were found to be within acceptance criteria of validation guidelines, indicating that the assay was applicable to the determination of the plasma concentrations of drug and its six metabolites. In conclusion, we developed an LC-MS/MS method for the quantitative analysis of APAP and its six metabolites in rat plasma, and this method appears to be useful for pharmacokinetic/toxicokinetic studies of APAP and its metabolites in rats.


Profiling Substrate Promiscuity of Wild-Type Sugar Kinases for Multi-fluorinated Monosaccharides.
Fluorinated sugar-1-phosphates are of emerging importance as intermediates in the chemical and biocatalytic synthesis of modified oligosaccharides, as well as probes for chemical biology. Here we present a systematic study of the activity of a wide range of anomeric sugar kinases (galacto- and N-acetylhexosamine kinases) against a panel of fluorinated monosaccharides, leading to the first examples of polyfluorinated substrates accepted by this class of enzymes. We have discovered four new N-acetylhexosamine kinases with a different substrate scope, thus expanding the number of homologs available in this subclass of kinases. Lastly, we have solved the crystal structure of a galactokinase in complex with 2-deoxy-2-fluorogalactose, giving insight into changes in the active site that may account for the specificity of the enzyme toward certain substrate analogs.


Fibula osteoseptocutaneous free flap in maxillary reconstruction.
The skin paddle in the fibula osteoseptocutaneous flap is thin, soft, and pliable, and it can be used for external skin coverage and intraoral linings. The flexibility of the fibula in three-dimensional positioning after multiple osteotomies is desirable in complex spatial skeletal reconstruction. The fibula osteoseptocutaneous flap is suitable for one-stage reconstruction of composite maxillary defects. The unique characteristics of the fibula osteoseptocutaneous flap and its application in the one-stage composite maxillary defect are discussed.


Associations of knee muscle force, bone malalignment, and knee-joint laxity with osteoarthritis in elderly people.
[Purpose] From the viewpoint of prevention of knee osteoarthritis, the aim of this study was to verify how muscle strength and joint laxity are related to knee osteoarthritis. [Subjects and Methods] The study subjects consisted of 90 community-dwelling elderly people aged more than 60 years (22 males, 68 females). Femorotibial angle alignment, knee joint laxity, knee extensors and flexor muscle strengths were measured in all subjects. In addition, the subjects were divided into four groups based on the presence of laxity and knee joint deformation, and the muscle strength values were compared. [Results] There was no significant difference in knee extensor muscle strength among the four groups. However, there was significant weakness of the knee flexor muscle in the group with deformation and laxity was compared with the group without deformation and laxity. [Conclusion] Decreased knee flexor muscle strengths may be involved in knee joint deformation. The importance of muscle strength balance was also considered.


Binary phase behavior and aggregation of dilute methanol in supercritical carbon dioxide: a Monte Carlo simulation study.
Configurational-bias Monte Carlo simulations in the Gibbs and isobaric-isothermal ensembles using the transferable potentials for phase equilibria force field were carried out to investigate the thermophysical properties of mixtures containing supercritical carbon dioxide and methanol. The binary vapor-liquid coexistence curves were calculated at 333.15 and 353.15 K and are in excellent agreement with experimental measurements. The self-association of methanol in supercritical carbon dioxide was investigated over a range of temperatures and pressures near the mixture critical point. The temperature dependence of the equilibrium constants for the formation of hydrogen-bonded aggregates (from dimer to heptamer) allowed for the determination of the enthalpy of hydrogen bonding, DeltaHHB, in supercritical carbon dioxide with values for DeltaHHB of about 15 kJ mol(-1) falling within the range of previously proposed values. No strong pressure dependence was observed for the formation of aggregates. Apparently the decrease of the entropic penalty and of the enthalpic benefit upon increasing pressure or solvent density mostly cancel each other's effect on aggregate formation.


Functional analysis of a novel de novo variant in PPP5C associated with microcephaly, seizures, and developmental delay.
We describe a proband evaluated through the Undiagnosed Diseases Network (UDN) who presented with microcephaly, developmental delay, and refractory epilepsy with a de novo p.Ala47Thr missense variant in the protein phosphatase gene, PPP5C. This gene has not previously been associated with a Mendelian disease, and based on the population database, gnomAD, the gene has a low tolerance for loss-of-function variants (pLI = 1, o/e = 0.07). We functionally evaluated the PPP5C variant in C. elegans by knocking the variant into the orthologous gene, pph-5, at the corresponding residue, Ala48Thr. We employed assays in three different biological processes where pph-5 was known to function through opposing the activity of genes, mec-15 and sep-1. We demonstrated that, in contrast to control animals, the pph-5 Ala48Thr variant suppresses the neurite growth phenotype and the GABA signaling defects of mec-15 mutants, and the embryonic lethality of sep-1 mutants. The Ala48Thr variant did not display dominance and behaved similarly to the reference pph-5 null, indicating that the variant is likely a strong hypomorph or complete loss-of-function. We conclude that pph-5 Ala48Thr is damaging in C. elegans. By extension in the proband, PPP5C p.Ala47Thr is likely damaging, the de novo dominant presentation is consistent with haplo-insufficiency, and the PPP5C variant is likely responsible for one or more of the proband's phenotypes.


Experimental concomitant toxoplasma and malaria infection in rats.
The effect of concomitant toxoplasma and malaria infection on the reticuloendothelial system was investigated in rats. This was evaluated by the level of plasmodial parasitaemia; humoral antibody response; effect on splenic weight; histopathological changes in thymus and spleen; histopathological and histochemical changes in liver. The parasitaemia appeared after 2 days in single malaria and concomitant infections. The peak was reached after 6 days with single and precedent malaria, and after 10 days with precedent toxoplasma. The clearance of parasitaemia was delayed to 30 days with concomitant infections instead of 14 days with single malaria. Higher than normal malarial antibody levels were reached with precedent toxoplasma, while the toxoplasma antibodies were lower than normal in both concomitant infections. There was a significant increase in splenic weight in both precedent malaria and toxoplasma, followed by a decrease which did not return to normal in case of precedent malaria. The thymus was packed with thymocytes in precedent malaria, while depletion in the cortex occurred in precedent toxoplasma. In the liver, there was glycogen depletion and decrease in succinic dehydrogenase activity in both concomitant infections. Choline esterase activity in precedent malaria was decreased and returned to normal on day 40 while in precedent toxoplasma the activity was normal all through the period. The alkaline phosphatase activity was decreased and returned to normal on day 40 in both concomitant infections.


Diamond optical vortex generator processed by ultraviolet femtosecond laser.
We propose a precise diamond micromachining method based on ultraviolet femtosecond laser direct writing and a mixed acid heating chemical treatment. The chemical composition of the attached clusters generated during laser ablation and their effects on morphologies were investigated in experiments. The averaged roughness of pristine and processed regions reduced to 0.64 nm and 9.4 nm from 20.5 nm and 37.4 nm, respectively. With this method, spiral zone plates (SZPs) were inscribed on a high-pressure high-temperature diamond surface as micro-optical vortex generators. The optical performances of the diamond SZPs were characterized in both experiments and simulations, which were very consistent with each other. This chemical auxiliary processing method will contribute greatly to the wide application of integration and miniaturization of diamond surface optical components.


Predicting the risk of local recurrence in patients with breast cancer: an approach to a new computer-based predictive tool.
To develop a new web-based tool, designated IBTR!, which integrates prognostic factors for local recurrence (LR) into a model to predict the 10-year risk of LR after breast conserving surgery (BCS) with or without radiation therapy (RT) with the goal of assisting with patient counseling and medical decision-making. All available randomized trials of BCS alone versus BCS plus RT, meta-analyses, and institutional reports were reviewed to identify the principal prognostic factors for LR after breast-conserving therapy. Patient age, margin status, lymphovascular invasion (LVI), tumor size, tumor grade, use of chemotherapy, and use of hormonal therapy were found to consistently and significantly impact LR across multiple studies. Based upon a composite analysis of the relevant published randomized and nonrandomized studies, relative risk (RR) ratios were estimated and assigned to each prognostic category. These RR ratios were entered into a mathematical model with the 10-year baseline rates of recurrence with and without RT, 7% and 24%, respectively, to predict patient-specific LR risk. Individual data entered into this computer model with regards to patient age, margin status, LVI, tumor size, tumor grade, use of chemotherapy, and use of hormonal therapy will generate patient-specific predicted 10-year LR risk with and without RT. A graphic representation of the relative risk reduction with RT will also be displayed alongside the numerical display. IBTR! is a first attempt at a computer model incorporating LR prognostic factors in an evidence-based fashion to predict individual LR risk and the potential additional benefit from RT.


Motor recovery and axonal plasticity with short-term amphetamine after stroke.
There is considerable debate regarding the efficacy of amphetamine to facilitate motor recovery after stroke or experimental brain injury. Different drug dosing and timing schedules and differing physical rehabilitation strategies may contribute to outcome variability. The present study was designed to ascertain (1) whether short-term amphetamine could induce long-term functional motor recovery in rats after an ischemic lesion modeling stroke in humans; (2) how different levels of physical rehabilitation interact with amphetamine to enhance forelimb-related functional outcome; and (3) whether motor improvement was associated with axonal sprouting from intact corticoefferent pathways originating in the contralesional forelimb motor cortex. After permanent middle cerebral artery occlusion, rats received vehicle or amphetamine during the first postoperative week (2 mg/kg, subcutaneously on Postoperative Days 2, 5, and 8). In both treatment groups, separate cohorts of rats were exposed to different levels of "physical rehabilitation" represented by a control environment, enriched environment, or enriched environment with additional sessions of focused activity. Skilled forelimb performance was assessed using the forelimb reaching task and ladder rung walk test. Anterograde tracing with biotinylated dextran amine was used to assess new fiber outgrowth to denervated motor areas. All treatment groups showed significant motor improvement as compared with control-housed, vehicle-treated animals. However, animals housed in an enriched environment that received amphetamine paired with focused activity sessions performed significantly better than any other treatment group and was the only group to achieve complete motor recovery (ie, reached preoperative performance) by 8 weeks. This recovery was associated with axonal sprouting into deafferentated subcortical areas from contralesional projection neurons. This study suggests that, after stroke, short-term pairing of amphetamine with sufficiently focused activity is an effective means of inducing long-term improvement in forelimb motor function. The anatomic data suggests that corticoefferent plasticity in the form of axonal sprouting contributes to the maintenance of motor recovery.


Radical cystectomy and the implications of comorbidity.
Radical cystectomy (RC) with pelvic lymph node dissection constitutes the gold standard treatment for muscle-invasive urothelial carcinoma of the bladder and high-risk nonmuscle-invasive disease refractory to instillation therapy. Although RC is performed with curative intent, the overall 5-year survival has been reported to be as low as 62% in the current literature. Various clinicopathological parameters determine post-RC outcome, but besides these, the role of comorbidity has gained increasing attention. In the current clinical practice, comorbidity information is quantified using various evaluated comorbidity indices. In this paper, we discuss the most recent data on comorbidity and performance indices assessed in patients undergoing RC and highlight their clinical implications.


Demand generation and social mobilisation for integrated community case management (iCCM) and child health: Lessons learned from successful programmes in Niger and Mozambique.
We present the approaches used in and outcomes resulting from integrated community case management (iCCM) programmes in Niger and Mozambique with a strong focus on demand generation and social mobilisation. We use a case study approach to describe the programme and contextual elements of the Niger and Mozambique programmes. Awareness and utilisation of iCCM services and key family practices increased following the implementation of the Niger and Mozambique iCCM and child survival programmes, as did care-seeking within 24 hours and care-seeking from appropriate, trained providers in Mozambique. These approaches incorporated interpersonal communication activities and community empowerment/participation for collective change, partnerships and networks among key stakeholder groups within communities, media campaigns and advocacy efforts with local and national leaders. iCCM programmes that train and equip community health workers and successfully engage and empower community members to adopt new behaviours, have appropriate expectations and to trust community health workers' ability to assess and treat illnesses can lead to improved care-seeking and utilisation, and community ownership for iCCM.


[Short-axis versus long-axis approach in ultrasound-guided central venous cannulation: an updated systematic review and meta-analysis].
To compare the success rate and safety of the short-axis (SAX) approach and long- axis (LAX) approach to ultrasound-guided central venous cannulation. Electronic bibliographic databases including PubMed, Cochrane Library, Science Direct, and Web of Science were searched for randomized controlled trials comparing ultrasound-guided central venous cannulation via the LAX and SAX approaches published during the period from January, 2011 to October, 2017. We extracted the data from the eligible studies and assessed the first-attempt success rate, overall puncture success rate and complication rate of the two approaches. The relative risk (RR) with the 95% CI was calculated using a fixed or random effects model. Seven randomized controlled trials were included for meta-analysis. The results showed that the first-attempt success rate was significantly higher in the SAX group than in the LAX group (RR=1.27, 95%CI: 1.11-1.46; P=0.0005, I2=49%), but the overall puncture success rate did not differ significantly between the two approaches (RR=1.04, 95%CI: 0.97-1.10; P=0.27, I2=84%). The incidence of accidental arterial puncture with the SAX approach was significantly lower than that with the LAX approach (RR=1.04; 95%CI: 1.01-1.08; P=0.01, I2=30%). Ultrasound-guided central venous cannulation via the SAX approach, as compared with the LAX approach, can increase first-attempt success rate and reduce the incidence of accidental arterial puncture.


Activation and blockade of the acetylcholine receptor-ion channel by the agonists (+)-anatoxin-a, the N-methyl derivative and the enantiomer.
The effects of (+)- and (-)-anatoxin-a (AnTX) and N-methylanatoxin (M-AnTX) on peripheral nicotinic ion channel activity were studied using high micromolar concentrations. Whereas (+)-AnTX is an effective agonist at nanomolar concentrations, (-)-AnTX and M-AnTX were effective at low micromolar concentrations. The binding of [3H]perhydrohistrionicotoxin to the nicotinic acetylcholine receptor-ion channel was stimulated by the above agonist concentrations, but [3H]perhydrohistrionicotoxin binding was inhibited at high micromolar concentrations of each of the toxins. In single channel recordings, these toxins exhibited ion channel blocking properties; the concentration- and voltage-dependent kinetics of each were essentially the same. In the case of (+)-AnTX, desensitization was also present at micromolar concentrations. These data show that ion channel blockade may be a property of many anatoxin-a analogs, and that in the particular case of analogs with low agonist potency, ion channel blockade may be a concomitant primary effect of the toxins. Stereospecificity and number of amine moieties did not influence the ion channel blocking characteristics in this series of molecules, although these factors strongly modified agonist potency.


Stroke Connectome and Its Implications for Cognitive and Behavioral Sequela of Stroke.
Systems-based approaches to neuroscience, using network analysis and the human connectome, have been adopted by many researchers by virtue of recent progress in neuroimaging and computational technologies. Various neurological disorders have been evaluated from a network perspective, including stroke, Alzheimer's disease, Parkinson's disease, and traumatic brain injury. Until now, dynamic processes after stroke and during recovery were investigated through multimodal neuroimaging techniques. Many studies have shown disruptions in structural and functional connectivity, including in large-scale neural networks, in patients with stroke sequela such as motor weakness, aphasia, hemianopia, neglect, and general cognitive dysfunction. A connectome-based approach might shed light on the underlying mechanisms of stroke sequela and the recovery process, and could identify candidates for individualized rehabilitation programs. In this review, we briefly outline the basic concepts of structural and functional connectivity, and the connectome. Then, we explore current evidence regarding how stroke lesions cause changes in connectivity and network architecture parameters. Finally, the clinical implications of perspectives on the connectome are discussed in relation to the cognitive and behavioral sequela of stroke.


Determination of the triterpenoid, betulinic acid, in Doliocarpus schottianus by HPLC.
The isolation, detection and quantification of betulinic acid in Doliocarpus schottianus are described. The isolation from the plant extract was made by column chromatography and centrifugal TLC, and betulinic acid was characterized by spectrometric methods. The detection and quantification were made by HPLC using a C18 column eluted with acetonitrile: water and detected at 210 nm. The results showed that the metabolite accumulates in the bark of the plant, but very small concentrations were also found in the leaves and wood.


The learning resources movement: its relationship to nurse education.
This paper addresses the place, position and potential of what is characterized as the 'Learning Resources Movement' in nurse education. It is based on experiences drawn from 10 years viewing resource use in general and nursing education, and, more recently, on observations arising from a research project looking at the growth within the school of nursing, of organizational structures for their development. It claims that the true potential of the movement has nowhere been fully realized. It sees the present position as indeterminate and misconceived. It claims that further development of such resources as are and will be available is intricately tied up with the professional development of nursing in a 'chicken-and-egg' situation. It argues that the stage has now been reached where the successful development of the one cannot proceed without the successful development of the other. Drawing on a fairy-tale analogy the paper views the Learning Resources Movement as a powerful tool for seeing through the shining surfaces of what to many are new curricular clothes and dealing with the basic truths of the situation underneath.


Modeling complex EEG data distribution on the Riemannian manifold toward outlier detection and multimodal classification.
The usage of Riemannian geometry for Brain-computer interfaces (BCIs) has gained momentum in re-cent years. Most of the machine learning techniques proposed for Riemannian BCIs consider the data distribution on a man-ifold to be unimodal. However, the distribution is likely to be multimodal rather than unimodal since high-data variability is a crucial limitation of electroencephalography (EEG). In this paper, we propose a novel data modeling method for considering complex data distributions on a Riemannian manifold of EEG covariance matrices, aiming to improve BCI reliability. Our method, Riemannian spectral clustering (RiSC), represents EEG covariance matrix distribution on a manifold using a graph with proposed sim-ilarity measurement based on geodesic distances, then clusters the graph nodes through spectral clustering. This allows flexibility to model both a unimodal and a multimodal distribution on a manifold. RiSC can be used as a basis to design an outlier detector named outlier detection Riemannian spectral clustering (oden-RiSC) and a multimodal classifier named multimodal classifier Riemannian spectral clustering (mcRiSC). All required parameters of odenRiSC/mcRiSC are selected in data-driven manner. More-over, there is no need to pre-set a threshold for outlier detection and the number of modes for multimodal classification. The experimental evaluation revealed odenRiSC can detect EEG outliers more accurately than existing methods and mcRiSC out-performed the standard unimodal classifier, especially on high-variability datasets. odenRiSC/mcRiSC are anticipated to contribute to making real-life BCIs outside labs and neuroer-gonomics applications more robust. RiSC can work as a robust EEG outlier detector and multimodal classifier.


[Leg lengthening using callotasis. 2. Evaluation of a group of patients with surgical treatment, discussion, literature].
In part 2 of the article the authors evaluate a group of 45 completed cases of lengthening of long bones, using the method of consecutive distraction according to Ilizarev. On average a lengthening of 5.4 cm was achieved. The authors evaluate the procedure of lengthening, the period taken by therapy in relation to the patients' age. The mean period of treatment was 5.7 weeks per 1 cm lengthening and it depends distinctly on the patient's age. In a total of 16 patients at the same time also correction of the axis of the leg was made. A major part of the investigation is devoted to evaluation of complications which, consistent with the literature, are classified as major, requiring further surgery, and minor ones which can be resolved without surgery during the lengthening procedure. Major complications were recorded 9 times, minor ones 8 times. Only in one instance the lengthening was terminated before the planed distraction was achieved. The authors evaluate these complications in relation to the length of distraction, the patient's age and the time when the lengthening was performed. At the same time they give instructions how to prevent complications and how to deal with them, if they arise. The conclusions and evaluation of the group of patients are dealt with in a detailed discussion where the authors compare their results with extensive references in the literature.


Two antigenotoxic chalcone glycosides from Mentha longifolia subsp. longifolia.
Mentha L. (Labiatae) species (mint) with their flavoring properties have been used in food industries for centuries. Besides they have a great importance in drug development and medicinal applications due to various bioactive compounds of several members of the genus. The aim of this study was to isolate bioactive compounds with antimutagenic potential by bio-guided fractionation and determine their structures by spectroscopic methods. The structural elucidation of the isolated compounds was done based on spectroscopic methods, including MALDI-MS, UV, IR, and 2D NMR experiments, and the bio-guided fractionation process was done by using the Ames/Salmonella test system. Henceforth, solely genotoxic and antigenotoxic potential of the new compounds were also confirmed up to 2 µM/plate by using the same test system. Two new chalcone glycosides: (βR)-β,3,2',6'-tetrahydroxy-4-methoxy-4'-O-rutinosyldihydrochalcone and (βR)-β,4,2',6'-tetrahydroxy-4'-O-rutinosyldihydrochalcone, were isolated from Mentha longifolia (L.) Hudson subsp. longifolia, together with known six flavonoid glycosides and one phenolic acid: apigenin-7-O-glucoside, luteolin-7-O-glucoside, apigenin-7-O-rutinoside, luteolin-7-O-rutinoside, apigenin-7-O-glucuronide, luteolin-7-O-glucuronide, rosmarinic acid. According to the antimutagenicity results, both new test compounds significantly inhibited the mutagenic activity of 9-aminoacridine in a dose-dependent manner at the tested concentrations from 0.8 to 2 µM/plate. (βR)-β,4,2',6'-Tetrahydroxy-4'-O-rutinosyldihydrochalcone showed the maximum inhibition rate as 75.94% at 2 µM/plate concentration. This is the first report that two new chalcone glycosides were isolated from Mentha longifolia subsp. longifolia and their antimutagenic potentials by using mutant bacterial tester strains. In conclusion, the two new chalcone glycosides showed a significant antigenotoxic effect on 9-aminoacridine-induced mutagenesis at tested concentrations.