Association of psychological distress and current cigarette smoking among Native Hawaiian and Pacific Islander adults and compared to adults from other racial/ethnic groups: Data from the National Health Interview Survey, 2014.
Cigarette smoking is the leading cause of preventable deaths worldwide. Research has documented an association between psychological distress and smoking among certain racial/ethnic groups but has not examined this association among Native Hawaiian and Pacific Islander (NHPI) adults. Data from the 2014 general and the NHPI-specific National Health Interview Surveys were analyzed at the University of Arkansas for Medical Sciences Regional Campus (Fayetteville, AR) in April 2021 to determine the association between current cigarette smoking and levels of psychological distress among NHPI adults and to assess the difference in the magnitude of that association among NHPI adults compared to adults of other racial/ethnic groups in the United States. The final analytic sample (n = 34,782) included 1,916 NHPI, 20,430 White, 4,725 Black, 2,001 Asian, and 5,710 Hispanic adults. A significant association between current cigarette smoking and psychological distress levels was found among NHPI adults as well as among adults from other racial/ethnic groups. There was no significant difference in the magnitude of the detected association among NHPI adults compared to the magnitude of the same association detected among adults of other racial/ethnic groups. However, this finding indicates race/ethnicity does not moderate the association between psychological distress and current cigarette smoking. Future studies should explore factors that may further explain the variation in current cigarette smoking within and across all racial/ethnic groups.


Options for radiotherapy in the treatment of liver metastases.
Technologic advances have provided the means to deliver tumoricidal doses of radiation therapy (RT) to patients with unresectable colorectal liver metastases, while avoiding critical normal tissues, providing the opportunity to use RT for curative intent treatment of metastatic disease. For the current report, the expanded role of RT, with its different techniques in the setting of metastatic colorectal cancer, from palliation to cure was reviewed.


Muscle function in patients with primary hyperparathyroidism.
The muscle contraction of the anterior tibial muscle was investigated by measurements of electrically stimulated and computer-analyzed muscle twitches in 18 unselected patients with primary hyperparathyroidism (HPT) and in 20 healthy control persons. The HPT patients had a lower muscle twitch tension (TT) at single stimulation, compared with the control group [76 +/- 24 N (SD) and 99 +/- 33 N respectively, P less than 0.05]. At high-frequency stimulation the difference in muscle force increased, and at 20 Hz stimulation the force in the HPT patients was 73% of that in the controls (P less than 0.01). There were no differences between the HPT patients and the control persons in neither contraction time nor half relaxation time at single muscle twitch nor in twitch potentiation after 20 and 90 seconds maximal voluntary contraction. The results indicate that patients with primary HPT have an impaired muscle function of probable importance for their symptoms of weakness and generalized fatigue.


Mechanisms of unusual response to lipid-lowering therapy: PCSK9 inhibition.
The efficacy of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition has broadened lipid-lowering therapy thus providing decreased risk in atherosclerotic cardiovascular disease. Unfortunately, the widespread use of PCSK9 inhibitors (PCSK9i), ie, monoclonal antibodies, has led to the findings of unusual responsiveness, ie, a phenomenon defined as an LDL-C reduction of <30% vs the average LDL-C reduction efficacy of 50-60%. This unusual responsiveness to PCSK9i is attributable to several factors, ie, lack of adherence, impaired absorption, poor distribution or early elimination as well as abnormal effects of PCSK9i in the presence of anti-antibodies or mutations in PCSK9 and LDLR. Unexpectedly increased lipoprotein (Lp)(a) also appear to contribute to the unusual responsiveness scenario. Identification of these responses and mechanisms underlying them are essential for effective management of LDL-C and cardiovascular risk. In this review, we describe plausible reasons underlying this phenomenon supported by findings of clinical trials. We also elaborate on the need for education and regular follow-up to improve adherence. Collectively, the review provides a summary of the past, present, and future of mechanisms and countermeasures revolving around unusual responses to PCSK9i therapy.


Nutrition and exercise.
The nutritional aspects of exercise are topics of popular interest, misconception, and active research. In this article, the authors review basic concepts of muscle metabolism; information concerning the role of exercise in weight loss; dietary supplements for athletes, including nutrition for competition; and eating disorders among those performing vigorous exercise.


Health-seeking behaviours of young women with sexually transmitted infections: Analysis of the 2014 Ghana Demographic and Health Survey.
Young people are at a disproportionately higher risk for sexually transmitted infections (STIs) due to biological factors, low awareness and limited access to sexual and reproductive health information and services. Untreated STIs can lead to major complications, including HIV, congenital infections, infertility, permanent disability and mortality. This study aimed to identify the salient factors associated with health-seeking behaviours of young women with a history of STIs in Ghana. We analysed data from the 2014 Ghana Demographic and Health Survey. In all, we analysed data from a weighted sample of 742 young women with a history of STIs. At the univariate level, frequencies and percentages were computed, while Chi-square analysis was computed at the bivariate level. Both crude and adjusted odds ratios were computed at the multivariable level using binary logistic regression. The findings showed that the majority (72%) of the participants sought treatment for STIs. Among the participants who sought treatment for STIs (n = 532), 26% sought treatment at a public hospital/polyclinic, 34% sought treatment at a chemical/drug store and 10% self-medicated. Seeking treatment for STIs was significantly associated with older age (20-24yrs), and higher socioeconomic and educational status. This study demonstrated that majority of the young women sought treatment for STIs. Seeking treatment for STIs was influenced by socio-demographic factors. These findings have implications for sexual and reproductive health policies and interventions in Ghana.


Modeling of Virtual Mechanical Circulatory Hemodynamics for Biventricular Heart Failure Support.
In this study, a mechanical circulatory support simulation tool was used to investigate the application of a unique device with two centrifugal pumps and one motor for the biventricular assist device (BVAD) support application. Several conditions-including a range of combined left and right systolic heart failure severities, aortic and pulmonary valve regurgitation, and combinations of high and low systemic and pulmonary vascular resistances-were considered in the simulation matrix. Relative advantages and limitations of using the device in BVAD applications are discussed. The simulated BVAD pump was based on the Cleveland Clinic pediatric continuous-flow total artificial heart (P-CFTAH), which is currently under development. Different combined disease states (n = 10) were evaluated to model the interaction with the BVAD, considering combinations of normal heart, moderate failure and severe systolic failure of the left and right ventricles, regurgitation of the aortic and pulmonary valves and combinations of vascular resistance. The virtual mock loop simulation tool (MATLAB; MathWorks®, Natick, MA) simulates the hemodynamics at the pump ports using a lumped-parameter model for systemic/pulmonary circulation characteristic inputs (values for impedance, systolic and diastolic ventricular compliance, beat rate, and blood volume), and characteristics of the cardiac chambers and valves. Simulation results showed that this single-pump BVAD can provide regulated support of up to 5 L/min over a range of combined heart failure states and is suitable for smaller adult and pediatric support. However, good self-regulation of the atrial pressure difference was not maintained with the introduction of aortic valve regurgitation or high systemic vascular resistance when combined with low pulmonary vascular resistance. This initial in silico study demonstrated that use of the P-CFTAH as a BVAD supports cardiac output and arterial pressure in biventricular heart failure conditions. A similar but larger device would be required for a large adult patient who needs more than 5 L/min of support.


MRIdb: medical image management for biobank research.
Clinical picture archiving and communications systems provide convenient, efficient access to digital medical images from multiple modalities but can prove challenging to deploy, configure and use. MRIdb is a self-contained image database, particularly suited to the storage and management of magnetic resonance imaging data sets for population phenotyping. It integrates a mature image archival system with an intuitive web-based user interface that provides visualisation and export functionality. In addition, utilities for auditing, data migration and system monitoring are included in a virtual machine image that is easily deployed with minimal configuration. The result is a freely available turnkey solution, designed to support epidemiological and imaging genetics research. It allows the management of patient data sets in a secure, scalable manner without requiring the installation of any bespoke software on end users' workstations. MRIdb is an open-source software, available for download at http://www3.imperial.ac.uk/bioinfsupport/resources/software/mridb .


Risk of adverse events with the use of augmentation therapy for the treatment of resistant depression.
Augmentation therapy is used for those situations where a patient's depression is either treatment-resistant, or partially and/or insufficiently responsive to treatment. It also may be used to attempt to induce a more rapid treatment response. Using drugs together may increase the risk of adverse effects, through potentiation of existing adverse effects or alterations in plasma concentrations of the drug. It is important that clinicians are aware of potential risks of augmentation therapy. Lithium augmentation of a tricyclic antidepressant is relatively well tolerated and the dangers are no greater than using these medications on their own. There are also no reports of serious adverse events when lithium is added to a monoamine oxidase inhibitor. With lithium augmentation of selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI) therapy there have been case reports of the development of a central serotonin syndrome, and thus caution must exercised. A serious concern when using a tricyclic antidepressant to augment an SSRI is the effect of the SSRI on the cytochrome P450 system and the resulting significant increase in tricyclic antidepressant blood concentrations. Augmentation with thyroid hormones appears to be well tolerated and effective. Case reports and open studies indicate that augmentation with buspirone and the psychostimulants, carbamazepine and valproic acid (valproate sodium) is effective and results in minimal adverse effects. However, there is no empirical evidence supporting these results. Recent work supports the tolerability and efficacy of pindolol augmentation. Considerable caution should be exercised when combining psychotropic drugs. The practitioner should only do so with a full knowledge of the compounds involved and their pharmacological properties.


Nose-to-brain delivery of perampanel formulated in a self-microemulsifying drug delivery system improves anticonvulsant and anxiolytic activity in mice.
Perampanel (PER) is a potent third-generation antiepileptic drug only available for oral administration. Additionally, PER has shown potential in managing epilepsy comorbidities such as anxiety. Previously, we demonstrated that the intranasal (IN) administration of PER, loaded in a self-microemulsifying drug delivery system (SMEDDS), improved brain-targeting and exposure in mice. Herein, we investigated PER brain biodistribution, its anticonvulsant and anxiolytic effects, and its potential olfactory and neuromotor toxicity after IN administration to mice (1 mg/kg). PER showed a rostral-caudal brain biodistribution pattern when administered intranasally. At short times post-nasal dosing, high PER concentrations were found in olfactory bulbs (olfactory bulbs/plasma ratios of 1.266 ± 0.183 and 0.181 ± 0.027 after IN and intravenous administrations, respectively), suggesting that a fraction of the drug directly reaches brain through the olfactory pathway. In the maximal electroshock seizure test, IN PER protected 60% of mice against seizure development, a substantially higher value than the 20% protected after receiving oral PER. PER also demonstrated anxiolytic effects in open field and elevated plus maze tests. Buried food-seeking test showed no signs of olfactory toxicity. Neuromotor impairment was found in rotarod and open field tests at the times of PER maximum concentrations after IN and oral administrations. Nevertheless, neuromotor performance was improved after repeated administrations. Compared with IN vehicle, PER IN administration decreased brain levels of L-glutamate (0.91 ± 0.13 mg/mL vs 0.64 ± 0.12 mg/mL) and nitric oxide (100 ± 15.62% vs 56.62 ± 4.95%), without interfering in GABA levels. Altogether, these results suggest that the IN PER delivery through the developed SMEDDS can be a safe and promising alternative to the oral treatment, which supports the design of clinical studies to evaluate the IN PER delivery to treat epilepsy and neurological-related conditions as anxiety.


Ca2+-dependent actin-binding phosphoprotein in Physarum polycephalum. I. Ca2+/actin-dependent inhibition of its phosphorylation.
When crude extracts of the slime mold Physarum polycephalum were incubated with ATP and Mg2+ at 35 degrees C, a peptide of approximately 42,000 Da was predominantly phosphorylated. The kinase, separated from the phosphorylatable peptide, phosphorylated neither actin nor fragmin, both proteins of 42,000 Da, the latter known to cap and shorten actin filaments in a Ca2+-dependent manner. The phosphorylatable peptide was phosphorylated only at threonine residue(s), and its phosphorylation was almost completely inhibited by micromolar concentrations of Ca2+ in the extracts. The Ca2+-dependent inhibition of the phosphorylation was reversed by the subsequent addition of ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid but not by trifluoperazine. The Ca2+-dependent inhibition of the phosphorylation required either actin or another, so far unidentified, protein(s) which is distinct from calmodulin. Fragmin reversed the Ca2+/actin-dependent inhibition of the phosphorylation. The Ca2+-dependent actin-binding phosphorylatable protein named Cap 42 (a + b), consisting of two distinct 42,000-Da peptides a and b, was purified to near homogeneity. Peptide b was identified as the phosphorylatable subunit. Substoichiometric amounts of Cap 42 (a + b) reduced the low shear viscosity of F-actin solutions.


He's here and he's gone; he's here and he's gone … The experiences of new mothers in rural Newfoundland and Labrador, Canada, whose partners work away from home.
Introduction Employment-related mobility (ERM) is a complex phenomenon that impacts family life. New mothers who have partners working away from home for intermittent and extended periods of time are particularly affected. As these families transition to parenting roles they are further challenged with the expectation that the mother manages sole responsibility for family and home life while her partner works away. A hermeneutic phenomenology approach was used to explore the experiences of new mothers on the island portion of rural Newfoundland and Labrador, Canada, whose partners participated in ERM. Participants were recruited through community health nurses and family resource center staff. Semi-structured interviews were conducted, audio-recorded, transcribed and analyzed following Ricoeur's approach. The essence of the experience of these 19 women was apparent in their stories of adjustment to periods of transition when their partner was working away from home. Five themes were generated from interpretation of the experiences of the participants: 'he's here and he's gone again', 'one-woman show', 'putting myself on the back burner', 'the routine goes out the window' and 'making it work'. While many women felt overwhelmed with the responsibilities of balancing family life, and often experienced loneliness, others described a smoother adaptation to an ERM lifestyle. The experiences of the mothers warrant consideration to inform health care providers, policymakers and community leaders to be more responsive to the emerging needs of families in these situations.


A Darwinian Laboratory of Multiple Contact Zones.
Barriers to gene flow between divergent populations result in contact (hybrid) zones. Locations where multiple contact zones overlap can be used in comparative studies asking: what mechanisms maintain barriers; what is the origin of the genetic variation involved; and do differences in life history affect the nature of barriers? In a review of 23 marine species' genetic divergence over a postglacial salinity gradient, many showed steep genetic clines supported by divergent selection and/or temporal or spatial segregation. Contacts were primary or secondary and shaped by ancestral variation sometimes involving inversions. The dispersal potential of species seemed less important in shaping clines. Studies of multispecies contact zones will increase our understanding of speciation, but we need to address the taxonomic bias and focus more on postzygotic isolation.


Genome segment ratios change during whitefly transmission of two bipartite cassava mosaic begomoviruses.
Cassava mosaic disease is caused by a complex of whitefly-transmitted begomoviruses, which often occur in co-infections. These viruses have bipartite genomes consisting of DNA-A and DNA-B that are encapsidated into separate virions. Individual viruses exist in plants and whitefly vectors as populations comprising both genome segments, which can occur at different frequencies. Both segments are required for infection, and must be transmitted for virus spread to occur. Cassava plants infected with African cassava mosaic virus (ACMV) and/or East African cassava mosaic Cameroon virus (EACMCV), in which the ratios of DNA-A:DNA-B titers differed between plants, were used to examine how titers of the segments in a plant relate to their respective probabilities of acquisition by whiteflies and to the titers of each segment acquired and subsequently transmitted by whiteflies. The probabilities of acquiring each segment of ACMV did not reflect their relative titers in the source plant but they did for EACMCV. However, for both viruses, DNA-A:DNA-B ratios acquired by whiteflies differed from those in the source plant and the ratios transmitted by the whitefly did not differ from one - the ratio at which the highest probability of transmitting both segments is expected.


Cingulate-mediated depressive symptoms in neurologic disease and therapeutics.
The depressive syndrome includes a number of symptoms that are clinically diverse. Research in the past decades has consistently demonstrated that the cingulate cortex plays an essential role in these manifestations. With anatomic studies initially showing volumetric changes, followed by the insights that functional imaging and physiology contributed to neuroscience and psychiatry, the distinct areas of the cingulate subdivisions were seen to have unique contributions. The subcallosal cingulate, with its functional responsivity to mood states and to antidepressant therapies, has been identified as a central node within the mood regulation network. In this chapter, detailed descriptions of the anatomic and functional changes that are seen in depression will be discussed. Finally, a focus on the development of deep brain stimulation in the subcallosal cingulate area will be used to emphasize the conceptualization of a network model with the cingulate as a hub, where engagement of remote areas of the depression network is needed to treat depression.


Boosting Reaction Homogeneity in High-Energy Lithium-Ion Battery Cathode Materials.
Conventional nickel-rich cathode materials suffer from reaction heterogeneity during electrochemical cycling particularly at high temperature, because of their polycrystalline properties and secondary particle morphology. Despite intensive research on the morphological evolution of polycrystalline nickel-rich materials, its practical investigation at the electrode and cell levels is still rarely discussed. Herein, an intrinsic limitation of polycrystalline nickel-rich cathode materials in high-energy full-cells is discovered under industrial electrode-fabrication conditions. Owing to their highly unstable chemo-mechanical properties, even after the first cycle, nickel-rich materials are degraded in the longitudinal direction of the high-energy electrode. This inhomogeneous degradation behavior of nickel-rich materials at the electrode level originates from the overutilization of active materials on the surface side, causing a severe non-uniform potential distribution during long-term cycling. In addition, this phenomenon continuously lowers the reversibility of lithium ions. Consequently, considering the degradation of polycrystalline nickel-rich materials, this study suggests the adoption of a robust single-crystalline LiNi0.8 Co0.1 Mn0.1 O2 as a feasible alternative, to effectively suppress the localized overutilization of active materials. Such an adoption can stabilize the electrochemical performance of high-energy lithium-ion cells, in which superior capacity retention above ≈80% after 1000 cycles at 45 °C is demonstrated.


About forbidden and weak reflections.
Reflections forbidden under the single scattering approximation are not expected to remain extinct for crystal thicknesses for which multiple scattering becomes important, except for reflections of the Gjönnes-Moodie type. However, it has been observed that in many crystals with the incident beam along a zone axis, such as diamond-like crystals along the [110] zone, reflections forbidden under the single scattering approximation remain very weak up to large thicknesses. This is hard to explain in terms of many-beam dynamical scattering in Fourier space. The picture becomes clear if one describes the scattering in real space in terms of the channelling of the electrons along the atom columns parallel to the zone axis. In that case the exit wave of each atom column can be described by the S-state model, which is radially symmetric around the centre of the atom column. As a consequence the exit wave shows the same symmetry as the projected potential, so that the reflections forbidden under the single scattering approximation remain extinct. This condition only breaks down when the crystal thickness becomes so large that the S-state model becomes invalid, which is a function of the distance between neighbouring atom columns and/or the tilt from the exact zone axis. The sensitivity for small tilts is also in agreement with very old observations that have not been explained thus far.


Semi-quantitative analysis of indigo by surface enhanced resonance Raman spectroscopy (SERRS) using silver colloids.
In this paper we report for the first time semi-quantitative analysis of indigo using surface enhanced Raman spectroscopy (SERS) and surface enhance resonance Raman spectroscopy (SERRS). Indigo, a dye widely used today in the textile industry, has been used, historically, both as a dye and as a pigment; the latter in both paintings and in printed material. The molecule is uncharged and largely insoluble in most solvents. The application of SERS/SERRS to the semi-quantitative analysis of indigo has been examined using aggregated citrate-reduced silver colloids with appropriate modifications to experimental protocols to both obtain and maximise SERRS signal intensities. Good linear correlations are observed for the dependence of the intensities of the SERRS band at 1151 cm(-1) using laser exciting wavelengths of 514.5 nm (R=0.9985) and 632.8 nm (R=0.9963) on the indigo concentration over the range 10(-7)-10(-5) and 10(-8)-10(-5) mol dm(-3), respectively. Band intensities were normalised against an internal standard (silver sol band at 243 cm(-1)). Resonance Raman spectra (RRS) of aqueous solutions of indigo could not be collected because of its low solubility and the presence of strong fluorescence. It was, however, possible to obtain RS and RRS spectra of the solid at each laser excitation wavelength. The limits of detection (L.O.D.) of indigo by SERS and SERRS using 514.5 and 632.8 nm were 9 ppm at both exciting wavelengths. Signal enhancement by SERS and SERRS was highly pH dependent due to the formation of singly protonated and possibly doubly protonated forms of the molecule at acidic pH. The SERS and SERRS data provide evidence to suggest that an excess of monolayer coverage of the dye at the surface of silver colloids is observed at concentrations greater than 7.85x10(-6) mol dm(-3) for each exciting wavelength. The data reported herein also strongly suggest the presence of multiple species of the indigo molecule.


Temporal changes in food preferences of wood mice (Apodemus sylvaticus L.).
Diet choice was determined for wild-caught wood mice (Apodemus sylvaticus L.), temporarily confined to cages in the field and offered a choice of 24-26 types of seeds and fruits in 2-h sessions throughout the night. The mice showed an overall preference for some foods over others. The set-up minimized influences on food preferences of predation risk, hunger, food availability and competition. Variation in food preferences was not attributable to differences between individuals, but followed a temporal pattern. The variety of foods eaten showed a bimodal pattern with peaks corresponding to the two most active periods at the beginning and end of the night. Both the amount of food eaten and variation in the amount diminished from the first to the second active period. An expected selection for carbohydrates early in the night and proteins at the end of the night was not found, but sugars were selected for early in the night. These results are discussed in relation to the conflict between an animal's continuous energy requirements and the essentially periodic activity of foraging.


Review article: 'true' re-infection of Helicobacter pylori after successful eradication--worldwide annual rates, risk factors and clinical implications.
The incidence of 'true' re-infection with Helicobacter pylori after successful eradication remains uncertain. To determine the worldwide rates, risk factors and clinical implications of 'true' re-infection of Helicobacter pylori. 'True' re-infection of H. pylori is defined as the situation where tests for H. pylori infection, which were negative for 12 months after eradication, become positive again at a later stage. Thirty six studies were identified through a literature search to be able to produce annual rates of 'true' re-infection, and data from 33 original articles were considered reliable and adequate in the further review. Generally, the reported rates varied from 0% to 23.4% in adults and from 1.9% to 9.6% in children. Most studies from developed countries reported rates of less than 1%, whereas relatively higher rates were reported in most of the developing countries. Small sample sizes included in the studies appeared to be associated with increased re-infection rates. Interfamilial transmission is the major cause of re-infection, although iatrogenic re-infection through contaminated endoscopic equipment has been reported. Helicobacter pylori re-infection is not a concern in a clinical setting, especially in the developed world; however, caution must be exercised in most developing countries.


Accomodative tone in children under general anesthesia.
To determine the effect of general anesthesia on the accommodative tone in children. Cohort study in an academic practice. In children under 12 years of age who were undergoing general anesthesia, cycloplegic refraction was measured using streak retinoscopy during an office visit. Within 6 months, streak retinoscopy without cycloplegia was performed under general anesthesia. The main outcome measure was the difference between retinoscopy under anesthesia and cycloplegic retinoscopy in children. In 41 children with an average age of 3.7 years (range, 0.8 to 11 years) retinoscopy under anesthesia yielded significantly more myopic measurements than cycloplegic retinoscopy for the sphere and spherical equivalent (P < 0.0001 for both) but was in good agreement with cycloplegic retinoscopy for cylinder power and axis. The average difference between retinoscopy under anesthesia and cycloplegic retinoscopy was -0.98 diopters (D) (95% limit of agreement, -3.08 D to +1.10 D) for the sphere, 0.08 D (95% limit of agreement, -0.67 D to +0.82 D) for the cylinder, and -0.94 D (95% limit of agreement, -3.01 D to +1.13 D) for the spherical equivalent. Retinoscopy under anesthesia was within 1 D of cycloplegic retinoscopy in 25 subjects (61%) for the sphere, in all subjects for the cylinder, and in 28 subjects (68.3%) for the spherical equivalent. Although general anesthesia reduced the accommodative tone in most children, it was still significant in some as compared to the tone found in cycloplegic retinoscopy. If an accurate measurement is essential, cycloplegia is recommended when measuring refraction in children under general anesthesia.


Measurement of plasma glucose, free fatty acid, lactate, and insulin for 24 h in patients with NIDDM.
Fasting and postprandial plasma glucose, free fatty acid (FFA), lactate, and insulin concentrations were measured at hourly intervals for 24 h in 27 nonobese individuals-9 with normal glucose tolerance, 9 with mild non-insulin-dependent diabetes mellitus (NIDDM, fasting plasma glucose less than 175 mg/dl), and 9 with severe NIDDM (fasting plasma glucose greater than 250 mg/dl). In addition, hepatic glucose production (HGP) was measured from midnight to 0800 in normal individuals and patients with severe NIDDM. Plasma glucose concentration was highest in patients with severe NIDDM, lowest in those with normal glucose tolerance, and intermediate in those with mild NIDDM (two-way ANOVA, P less than .001). Variations in plasma FFA and lactate levels of the three groups were qualitatively similar, with lowest concentrations seen in normal individuals, intermediate levels in the group with mild NIDDM, and the highest concentration in those with severe NIDDM (two-way ANOVA, P less than .001). Of particular interest was the observation that plasma FFA concentrations were dramatically elevated from midnight to 0800 in patients with severe NIDDM. The 24-h insulin response was significantly increased in patients with mild NIDDM, with comparable values seen in the other two groups. Values for HGP fell progressively throughout the night in normal individuals and patients with severe NIDDM, despite a concomitant decline in plasma glucose and insulin levels. Although the magnitude of the fall in HGP was greater in NIDDM, the absolute value was significantly (P less than .001) greater than normal throughout the period of observation.(ABSTRACT TRUNCATED AT 250 WORDS)


The anti-leukaemic effects and the mechanism of sodium selenite.
The anti-proliferative effects of selenium were studied both in vivo and in vitro. At a selenium concentration of 0.6 micrograms/ml, cells from patients with ALL-L1, L2 and AML-M1, M3 and M5 were more sensitive than cells from patients with CML. Cells from patients with AML-M2, CLL and leukaemic lymphoma were least sensitive. Normal bone marrow or peripheral blood cells were not sensitive to selenium at this concentration. In the mouse leukaemia models (L797, L615, L7712), the sensitivity of leukaemic cells were: L797 (93% cytotoxicity) greater than L615 (49.7% cytotoxicity) greater than L7712 (4.4% cytotoxicity). Sodium selenite injected i.p. increased the longevity of L797-inoculated mice. Administration of 40 micrograms selenium daily for 7 days resulted in a significant increase in the longevity of mice inoculated with 10(5) L797 cells. However, no remarkable increase of the longevity was observed in either L615- or L7712-inoculated mice after treatment with sodium selenite for 7 days. Treatment of the HL-60 leukaemic cell line with selenium caused a dose- and time-related decrease in DNA, RNA and protein syntheses as measured by [3H]-thymidine, [3H]-uridine and [3H]-leucine uptake respectively. The inhibitory effect of selenium on DNA synthesis was reversed when selenium was removed from the medium, demonstrating that selenium-induced inhibition of DNA synthesis was due to interference with DNA biosynthesis rather than DNA template damage. These results suggest that the anti-leukaemic effect of sodium selenite is associated with inhibition of DNA replication, transcription and translation.


Mechanoelectrical transduction by hair cells of the bullfrog's sacculus.
Hair cells of the internal ear respond to excitatory mechanical stimulation of their hair bundles by the rapid opening of poorly cation-selective transduction channels. These channels, which are located near the bundles' tips, may be gated by forces applied through elastic linkages between adjacent stereocilia.


Novel biosensing platform based on self-assembled supramolecular hydrogel.
The supramolecular hydrogel self-assembled from α-cyclodextrin (α-CD) and an amphiphilic triblock copolymer was used for the first time as a biosensing platform by the in-situ incorporation of horseradish peroxidase and polyaniline (PANI) nanoparticles. It was found that the used triblock copolymer could disperse well PANI nanoparticles in aqueous system and then interact with α-CD in the presence of horseradish peroxidase for the formation of supramolecular hydrogel composite. The content of PANI nanoparticles was found to affect the gelation time and gel strength. The circular dichroism analyses showed that the entrapped horseradish peroxidase could retain its native conformation. By electrochemical experiments, the incorporated PANI nanoparticles were confirmed to improve the current response and enzymatic activity, and the fabricated biosensor was found to provide a fast amperometric response to hydrogen peroxide.


[Macular lymphocytic arteritis and periarteritis nodosa: A case report showing diagnostic and nosological challenges posed by these two entities].
Macular lymphocytic arteritis is a recently described type of cutaneous vasculitis involving vessels of medium size. Authors consider it as a form of polyarteritis nodosa. Herein we report a case of macular lymphocytic arteritis during the course of which periarteritis nodosa appeared. A 50-year-old man, with no history other than chronic venous insufficiency of the lower limbs, presented with an asymptomatic eruption involving all four limbs, mainly the lower limbs, and appearing in episodes. Physical examination revealed brown macules, in some cases outlining the configuration of livedo reticularis. Laboratory findings were normal except for the presence of low levels of anticardiolipin activity at diagnosis, which had subsided three months later. Histological examination of the skin biopsy showed lymphocytic arteritis with some histiocytes and neutrophils, as well as an eosinophilic ring of parietal necrosis. Six months later, the patient developed multineuritis, leading to the diagnosis of polyarteritis nodosa. A diagnosis of cutaneous polyarteritis nodosa could also have been made based on the association of cutaneous livedo and locoregional polyneuritis without systemic involvement. The diagnosis of macular lymphocytic arteritis is based upon clinical and histological findings and upon disease progression. This entity seems to belong to the same spectrum as periarteritis nodosa, especially in the cutaneous form. Given the lack of knowledge concerning progression from macular lymphocytic arteritis to nodosa periarteritis, close patient monitoring is called for, as illustrated by our case report.


Use of venography as an aid in varicocelectomy.
Venography has been proposed as an aid in preventing persistent varicoceles after internal spermatic vein ligation. Since 1984, 10 patients between 4 and 18 years old underwent successful outpatient varicocelectomy with high ligation and intraoperative internal spermatic venography to assure that all appropriate veins and collaterals had been isolated before ligation.


Tetrahydrohomofolate polyglutamates as inhibitors of thymidylate synthase and glycinamide ribonucleotide formyltransferase in Lactobacillus casei.
In order to determine the mechanism for the effects of homofolates on growth of Lactobacillus casei, polyglutamated derivatives of homofolate (HPteGlu), dihydrohomofolate and tetrahydrohomofolate (H4HPteGlu) were synthesized and tested as inhibitors of folate-requiring enzymes. The following L. casei enzymes were examined: thymidylate synthase (TS), glycinamide ribonucleotide formyltransferase (GARFT), aminoimidazolecarboxamide ribonucleotide formyltransferase, serine hydroxymethyltransferase and dihydrofolate reductase. Polyglutamates of (6R,S)-H4HPteGlu are potent inhibitors of TS and GARFT. For example, the IC50 values of (6R,S)-H4HPteGlu6 are 0.7 microM for TS and 0.3 microM for GARFT. By contrast, the value for HPteGlu6 is greater than 10 microM for both TS and GARFT. Inhibition of TS and GARFT by (6R,S)-H4HPteGlu derivatives increases with polyglutamate chain length. For TS, the Glu5 and Glu6 derivatives of (6R,S)-H4HPteGlu are 20 and 30 times more potent than the monoglutamate, respectively. For GARFT, the Glu2-6 derivatives are 2-3 times more potent than Glu1. Inhibition of TS and GARFT by (6R,S)-H4HPteGlu polyglutamates is almost entirely due to the unnatural (6R) diastereomer at C-6. Homofolate derivatives are only weak inhibitors of aminoimidazolecarboxamide ribonucleotide formyltransferase, serine hydroxymethyltransferase, and dihydrofolate reductase. We conclude that both TS and GARFT are potential targets of (6R)-H4HPteGlu polyglutamates.


CAS directly interacts with vinculin to control mechanosensing and focal adhesion dynamics.
Focal adhesions are cellular structures through which both mechanical forces and regulatory signals are transmitted. Two focal adhesion-associated proteins, Crk-associated substrate (CAS) and vinculin, were both independently shown to be crucial for the ability of cells to transmit mechanical forces and to regulate cytoskeletal tension. Here, we identify a novel, direct binding interaction between CAS and vinculin. This interaction is mediated by the CAS SRC homology 3 domain and a proline-rich sequence in the hinge region of vinculin. We show that CAS localization in focal adhesions is partially dependent on vinculin, and that CAS-vinculin coupling is required for stretch-induced activation of CAS at the Y410 phosphorylation site. Moreover, CAS-vinculin binding significantly affects the dynamics of CAS and vinculin within focal adhesions as well as the size of focal adhesions. Finally, disruption of CAS binding to vinculin reduces cell stiffness and traction force generation. Taken together, these findings strongly implicate a crucial role of CAS-vinculin interaction in mechanosensing and focal adhesion dynamics.


Phylogenetic and functional diversity of alkane degrading bacteria associated with Italian ryegrass (Lolium multiflorum) and Birdsfoot trefoil (Lotus corniculatus) in a petroleum oil-contaminated environment.
Twenty-six different plant species were analyzed regarding their performance in soil contaminated with petroleum oil. Two well-performing species, Italian ryegrass (Lolium multiflorum var. Taurus), Birdsfoot trefoil (Lotus corniculatus var. Leo) and the combination of these two plants were selected to study the ecology of plant-associated, culturable alkane-degrading bacteria. Hydrocarbon degrading bacteria were isolated from the rhizosphere, root interior and shoot interior and subjected to the analysis of 16S rRNA gene, the 16S and 23S rRNA intergenic spacer region and alkane hydroxylase genes. Furthermore, we investigated whether alkane hydroxylase genes are plasmid located. Higher numbers of culturable, alkane-degrading bacteria were associated with Italian ryegrass, which were also characterized by a higher diversity, particularly in the plant interior. Only half of the isolated bacteria hosted known alkane hydroxylase genes (alkB and cytochrome P153-like). Degradation genes were found both on plasmids as well as in the chromosome. In regard to application of plants for rhizodegradation, where support of numerous degrading bacteria is essential for efficient break-down of pollutants, Italian ryegrass seems to be more appropriate than Birdsfoot trefoil.


Botulinum toxin-A injections for idiopathic overactive bladder: a systematic review and meta-analysis.
To review the current evidence on the efficacy and safety of botulinum toxin-A in the management of idiopathic overactive bladder (OAB). A systematic search of PubMed, Embase and the Cochrane Central Search Library was performed. All randomized controlled trials comparing botulinum toxin-A with placebo, different doses and injection techniques, in patients with idiopathic OAB was included. The analyzed outcomes were quantification of symptoms, urodynamic outcomes, quality of life and adverse events. A total of 1,020 participants from 12 randomized controlled trials were included. Botulinum toxin-A was associated with less urinary frequency, less incontinence episodes, improvement in quality of life, higher post-void residual-related catheterization and higher urinary tract infection. Doses of 100-300 U were not consistently differentiated from each other in voiding diary, quality of life and urge urinary incontinence. No statistically significant difference was seen between bladder body and bladder base, bladder body and bladder body plus trigone in urinary retention and urinary tract infection. Botulinum toxin-A is associated with significant improvement in OAB symptoms in patients with idiopathic OAB. However, there is a higher incidence of postoperative urinary retention and urinary infection compared to placebo. Low-dose botulinum toxin-A seems to be the optimum dose that appropriately balances the benefits with adverse events. Trigone inclusion seems as safe and effective as trigone-sparing injection.


Severe rhabdomyolysis-induced acute kidney injury following concomitant use of Genvoya® (EVG/COBI/FTC/TAF) and simvastatin; a case report.
Genvoya® (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide) is a recent single regimen for the treatment of Human Immunodeficiency Virus (HIV). However, because of its complexity, it is difficult to predict drug interactions, especially when associated with HMG-CoA reductase inhibitors and/or in the setting of other comorbidities. We discuss the mechanisms of these potential drug interactions as the cause of rhabdomyolysis and acute kidney injury in the context of prior and current medication therapy with possible underlying liver and kidney dysfunction. We describe the case of a 54-year-old man diagnosed with HIV who developed severe rhabdomyolysis-induced anuric acute kidney injury (AKI) requiring renal replacement therapy following introduction of Genvoya® concomitantly with simvastatin, in the context of recently diagnosed hepatitis C and hepatitis A. Haemodialysis was continued over 5 weeks followed by progressive clinical and biological improvements. Five months later, a new antiretroviral regimen was started and has been well tolerated. Simvastatin, as well as lovastatin, because of their CYP3A4 metabolism, and to a lesser extent atorvastatin, which is only partially metabolized by CYP3A4, are the HMG-CoA reductase inhibitors with the greatest risk of drug interactions and should not be used in patients under HIV-therapy. Patients receiving HMG-CoA reductase inhibitors should be monitored regularly for the occurrence of muscular adverse effects and drug interactions should be considered with each new prescription or change in clinical status. There are many online tools that enable clinicians to rapidly check for drug interactions. We recommend the one from the University of Liverpool for patients under HIV-therapy ( https://www.hiv-druginteractions.org/checker ), while for patients under hepatitis C-therapy, we advise to consult http://www.hep-druginteractions.org/ . This case illustrates the importance of multidisciplinary collaboration in the treatment of HIV-positive patients because of their complexity, associated comorbidities and the potential of multiple drug-drug interactions potentially exacerbated by underlying liver and/or kidney dysfunction.


Site density of the sodium-calcium exchange carrier in reconstituted vesicles from bovine cardiac sarcolemma.
The site density of the Na2+-Ca2+ exchanger in bovine cardiac sarcolemma was estimated from measurements of the fraction of reconstituted proteoliposomes exhibiting exchange activity. Sarcolemmal vesicles were solubilized with 1% Triton X-100 in the presence of either 100 mM NaCl or 100 mM KCl; after a 20-40-min incubation period on ice, sufficient KCl, NaCl, CaCl2, and soybean phospholipids were added to each extract to give final concentrations of 40 mM NaCl, 120 mM KCl, 0.1 mM CaCl2, and 10 mg/ml phospholipid. These mixtures were then reconstituted into proteoliposomes, and the rate of 45Ca2+ isotopic exchange was measured under equilibrium conditions. Control studies showed that Na+-Ca2+ exchange activity was completely lost if Na+ was not present during solubilization. The difference in 45Ca2+ uptake between vesicles initially solubilized in the presence or absence of NaCl therefore reflected exchange activity and corresponded to 3.1 +/- 0.3% of the total 45Ca2+ uptake by the entire population of vesicles, as measured in the presence of the Ca2+ ionophore A23187. Assuming that each vesicle with exchange activity contained 1 molecule of the Na+-Ca2+ exchange carrier, a site density of 10-20 pmol/mg of protein for the exchanger was calculated. The Vmax for Na+-Ca2+ exchange activity in the proteoliposomes was approximately 20 nmol/mg of protein.s which indicates that the turnover number of the exchange carrier is 1000 s-1 or more. Thus, the Na+-Ca2+ exchanger is a low density, high turnover transport system.


The fatty acid levels of rat alpha-fetoprotein derived from fetuses, pregnancy and hepatoma sera.
The fatty acid levels of alpha-fetoprotein (AFP) isolated from term rat fetuses is about half that of similar human preparations. Arachidonic and docosahexaenoic acids constitute about 33% of the total fatty acids in the rat AFP isolates. The AFP isolated from rat maternal and hepatoma sera have relatively low levels of these fatty acids. A comparison of the fatty acid contents of selected tissues from pregnant and non-pregnant rats does not show differences which might reflect the variable fatty acid levels of the fetal and maternal source AFP preparations.


Molecular cloning of the aspartate 4-decarboxylase gene from Pseudomonas sp. ATCC 19121 and characterization of the bifunctional recombinant enzyme.
L-Aspartate 4-decarboxylase (Asd) is a major enzyme used in the industrial production of L-alanine. Its gene was cloned from Pseudomonas sp. ATCC 19121 and characterized in the present study. The 1,593-bp asd encodes a protein with a molecular mass of 59,243 Da. The Asd from this Pseudomonas strain was considerably homologous to other Asds and aminotransferases, and has evolved independently of these enzymes from gram-positive microbes. Productivity rate of the C-terminal His-tagged fusion Asd was at 33 mg/l of Escherichia coli transformant culture. The kinetic parameters K (m) and V (max) of the fusion protein were 11.50 mM and 0.11 mM/min, respectively. Gel filtration analysis demonstrated that Asd is a dodecamer at pH 5.0 while 4.4 % of the recombinant protein dissociated into dimer when the pH was increased to 7.0. Asd exhibited its maximum activity at pH 5.0 and specific activity of 280 U/mg, and remained stable over a broad range of pH. The optimum temperature for Asd reaction was 45 degrees C, and 92 % of the activity remained when the enzyme was incubated at 40 degrees C for 40 min. This enzyme did not have any preferred divalent cation for catalysis. The recombinant Asd also exhibited aminotransferase activity when D,L-Asp, L-Glu, L-Gln, and L-Ala were utilized as substrates. However, the decarboxylation activity of L-aspartate was 2,477 times higher than its aminotransferase activity. The present study is the first investigation on the important biochemical properties of the purified recombinant Asd.


[Multimodal therapy of locally advanced prostate cancer].
Locally advanced prostate cancer (LAPCA) comprises about 5-10 % of all newly diagnosed prostate cancers and is associated with the highest prostate cancer specific mortality (approximately 8-20 %). LAPCA is defined by the presence of extraprostatic extension, seminal vesicle invasion, and bladder neck infiltration of pelvic lymph node metastases. It is evident that prognosis can only be improved by interdisciplinary multimodality treatment strategies. Adequate local staging by multiparametric MRI is one of the cornerstones for an individualized, risk-adapted treatment approach. This might consist of extended radical prostatectomy with an extended pelvic lymphadenectomy or intensity-modulated radiation therapy with androgen deprivation as the primary local therapeutic approach. Both treatment strategies may be combined with neoadjuvant or adjuvant radiation therapy or salvage surgery. Combination with neoadjuvant or adjuvant chemotherapy and new androgen receptor pathway inhibitors might also be possible. This article summarizes the current treatment strategies for LAPCA.


Can we imagine how objects look from other viewpoints?
Many psychologists who study cognition believe that perception achieves object-centered representations that make it possible to extract representations of how the object would appear from differing viewpoints. Others believe we can achieve representations of how an object would appear by a process of visualization or mental rotation. We report experiments in which the subject tries to imagine how three-dimensional novel wire objects would appear from positions other than the one they are in. Subjects are unable to perform this task unless they make use of strategies that circumvent the process of visualization. It is suggested that the linear increase in time required to succeed in mental rotation tasks as a function of the angular discrepancy between the figures compared is the result of increasing difficulty rather than of the time required for rotation.


Sequential iodine-mediated diallylsilane rearrangement/asymmetric dihydroxylation: Synthesis and reactions of enantioenriched oxasilacycles.
Products from an iodine-mediated diallylsilane rearrangement were taken into an asymmetric dihydroxylation (AD) reaction resulting in the formation of diastereomeric 6-membered oxasilacycles. Removal of the epimeric stereocenter among this mixture of diastereomers by elimination of iodine produced a single enantioenriched cyclic allyl silyl ether. The resulting allyl silane was then successfully engaged in several further transformations, providing an alternative means to prepare useful intermediates for enantioselective synthesis.


Orbital complication of acute ethmoiditis: A Tunisian paediatric cross sectional study.
The anatomical and developmental particularities of sinus cavities in paediatric population lead acute ethmoiditis to be the earliest form of sinusitis in children. Orbital complications are frequent and could lead to visual and neurological impairment. This study investigated the clinical, biological and radiological features of orbital complications. We identified the predictive factors of severe ophthalmological lesions and/or associated cerebral complications of acute ethmoiditis. This cross sectional study included all patients identified as having orbital extension of acute ethmoiditis in the database of a single academic paediatric care centre over a period of 14 years. All orbital and cerebral Scans of the included patients were reviewed and the cohort was classified using Chandler's classification as having less severe lesions (Chandler's 1 and 2) or more serious lesions (Chandler's 3, 4 and 5). In total, 16 patients (12 girls and 4 boys) were included among 39 consecutives cases of ethmoiditis recessed with a complication rate of 41%. Average consultation delay was 4.88 days. The mean age was 4.37 years. Fever was objectified in 13 cases (81%). Six patients (37.5%) had exophthalmos. Orbital extension spectrum was: stage I (n = 4, 25%), stage II (n = 4, 25%), stage III (n = 6, 37.5%), stage IV (n = 1, 6.5%), stage V (n = 1, 6.5%) and intra cranial extension was associated in two cases. Univariate analysis showed that fever, exophthalmos, ophthalmoplegia, positive CRP, age and white blood cells count were not associated with more severe lesions in the CT scan. Initially, all children received intravenous antibiotic treatment. Association of multiple antibiotics was prescribed in 75% of the cases. With 21.07 days ± 5.51 days as a total treatment duration. Only Four patients underwent surgical treatment. Orbital complications of ethmoiditis are frequent. No clinical or biological criteria seem to predict the severity of orbital lesions. Both orbital and brain CT scan could help detect eventual complications on time to adapt antibiotic treatment and eventually bring forward surgical intervention.


Regulation of mitochondrial function by hydroquinone derivatives as prevention of platelet activation.
Platelet activation plays an essential role in the pathogenesis of thrombotic events in different diseases (e.g., cancer, type 2 diabetes, Alzheimer's, and cardiovascular diseases, and even in patients diagnosed with coronavirus disease 2019). Therefore, antiplatelet therapy is essential to reduce thrombus formation. However, the utility of current antiplatelet drugs is limited. Therefore, identifying novel antiplatelet compounds is very important in developing new drugs. In this context, the involvement of mitochondrial function as an efficient energy source required for platelet activation is currently accepted; however, its contribution as an antiplatelet target still has little been exploited. Regarding this, the intramolecular hydrogen bonding of hydroquinone derivatives has been described as a structural motif that allows the reach of small molecules at mitochondria, which can exert antiplatelet activity, among others. In this review, we describe the role of mitochondrial function in platelet activation and how hydroquinone derivatives exert antiplatelet activity through mitochondrial regulation.


18F-FHBG PET-CT Reporter Gene Imaging of Adoptive CIK Cell Transfer Immunotherapy for Breast Cancer in a Mouse Model.
To further improve the efficiency of adoptively transferred cytokine-induced killer (CIK) cell immunotherapy in breast cancer (BC), a reliable imaging method is required to visualize and monitor these transferred cells in vivo. Herpes simplex virus 1-thymidine kinase (HSV1-TK) and 9-(4-[18F]fluoro-3-(hydroxymethyl)butyl)guanine (18F-FHBG) were used as a pair of reporter gene/reporter probe for positron emission tomography (PET) imaging in this study. Following the establishment of subcutaneous BC xenograft-bearing nude mice models, induced human CIK cells expressing reporter gene HSV1-TK through lentiviral transduction were intravenously injected to nude mice. γ-radioimmunoassay was used to determine the specific uptake of 18F-FHBG by these genetically engineered CIK cells expressing HSV1-TK in vitro, and 18F-FHBG micro positron emission tomography-computed tomography (PET-CT) imaging was performed to visualize these adoptively transferred CIK cells in tumor-bearing nude mice. Specific uptake of 18F-FHBG by CIK cells expressing HSV1-TK was clearly observed in vitro. Consistently, the localization of adoptively transferred CIK cells in tumor target could be effectively visualized by 18F-FHBG micro PET-CT reporter gene imaging. PET-CT reporter gene imaging using 18F-FHBG as a reporter probe enables the visualization and monitoring of adoptively transferred CIK cells in vivo.


Increased familial risk and evidence of genetic factor in migraine.
To investigate familial occurrence of migraine with and without aura. Familial occurrence of migraine with and without aura among first degree relatives and spouses of probands with migraine with or without aura and those who had never had migraine. All interviews of first degree relatives and spouses were done blindly by a neurological resident. The operational diagnostic criteria of the International Headache Society were used. General population from Copenhagen County. The 378 probands had 1109 first degree relatives and 229 spouses. Patterns of familial aggregation of migraine with and without aura as assessed by calculation of the population relative risk. Compared with the general population the first degree relatives of probands with migraine without aura had 1.9 times the risk of migraine without aura and 1.4 times the risk of migraine with aura. The first degree relatives of probands with migraine with aura had nearly four times the risk of migraine with aura and no increased risk of migraine without aura. The first degree relatives of probands who had never had migraine had no increased risk of migraine either with or without aura. Spouses of probands with migraine without aura had 1.4 times the risk of migraine without aura whereas spouses of probands with migraine with aura had no increased risk of migraine with aura. The different familial patterns indicate that migraine without aura and migraine with aura have a different aetiology. Migraine without aura seems to be caused by a combination of genetic and environmental factors whereas migraine with aura is probably determined largely or exclusively by genetic factors.


[Mesothelioma].
Malignant mesotheliomas are rare and aggressive tumours arising from mesothelial cells of the pleura and peritoneum. Infrequent sites of origin are the pericardium and tunica vaginalis testis. More than 80% of mesotheliomas are localized in the pleura. Men are more frequently affected than women. The median age is >60 years. Asbestos exposure is the best known aetilogical risk factor and is reported in 54-90% of patients. In Germany, malignant mesotheliomas caused by occupational asbestos exposure are compensated as occupational disease since 1977. Several neoplastic and non-neoplastic lesions like metastasis, sarcomas, lymphomas or pleuritis with reactive mesothelial proliferation have to be distinguished from malignant mesotheliomas. Especially, the pathohistological differentiation between atypical reactive mesothelial proliferation from malignant mesothelioma is a diagnostic challenge.


A booster hepatitis B vaccine for children with maternal HBsAg positivity before 2 years of age could effectively prevent vaccine breakthrough infections.
The long-term protective effect of hepatitis B vaccine (HepB), the incidence of hepatitis B virus (HBV) vaccine breakthrough infections (VBIs), and whether a booster HepB is necessary remain to be clarified in children born to mothers with chronic HBV infection. Based on a long-term follow-up prospective cohort of 1177 hepatitis B surface antigen (HBsAg)-positive mothers and their paired infants which was established from 2009 to 2011, total 454 children with immunoprophylaxis success as determined by postvaccination serologic testing (PVST) at 7 months old were included in this study. Among the 454 children, 246 never had a booster HepB, and 208 children received a booster HepB from 1 to 5 years of age. Multivariate logistic regression analysis was used to analyse the risk factors for HBV VBIs. The hepatitis B surface antibody (anti-HBs) levels declined sharply from 7 months to 2 years old, and the anti-HBs seronegative rate in the children increased significantly from 2 years old. A total of 31 (6.83%) of the 454 children experienced VBIs, of which 7 had overt and 7 had occult HBV infections. Notably, 14 (45.16%) of the 31 children with VBIs were diagnosed at 2 years old, and all of them had anti-HBs positivity (> 10 mIU/mL) at 1 year old. Maternal hepatitis B e antigen (HBeAg) positivity, higher HBV DNA and HBsAg levels, lower initial infant anti-HBs levels and not receiving a booster HepB were independent risk factors for VBIs. The incidence of VBIs was significantly lower in children with a booster HepB than in nonboosted children (0.50 vs. 11.90%, P < 0.001), and none of the boosted children developed overt or occult HBV infection. The anti-HBs levels of 76.67% for the children with VBIs in the nonboosted group indicated positivity before VBIs was detected. After the primary full immunization with HepB, children born to mothers with chronic HBV infection, especially the children with maternal HBeAg positivity, high HBV DNA levels, high HBsAg levels and/or low initial infant anti-HBs levels, were at a high risk of VBIs, and a booster HepB for these children before 2 years old, instead of when their anti-HBs level is < 10 mIU/mL, could reduce the incidence of VBIs.


Theoretical and computational validation of the Kuhn barrier friction mechanism in unfolded proteins.
A long time ago, Kuhn predicted that long polymers should approach a limit where their global motion is controlled by solvent friction alone, with ruggedness of their energy landscapes having no consequences for their dynamics. In contrast, internal friction effects are important for polymers of modest length. Internal friction in proteins, in particular, affects how fast they fold or find their binding targets and, as such, has attracted much recent attention. Here we explore the molecular origins of internal friction in unfolded proteins using atomistic simulations, coarse-grained models and analytic theory. We show that the characteristic internal friction timescale is directly proportional to the timescale of hindered dihedral rotations within the polypeptide chain, with a proportionality coefficient b that is independent of the chain length. Such chain length independence of b provides experimentally testable evidence that internal friction arises from concerted, crankshaft-like dihedral rearrangements. In accord with phenomenological models of internal friction, we find the global reconfiguration timescale of a polypeptide to be the sum of solvent friction and internal friction timescales. At the same time, the time evolution of inter-monomer distances within polypeptides deviates both from the predictions of those models and from a simple, one-dimensional diffusion model.


Structure of a headful DNA-packaging bacterial virus at 2.9 Å resolution by electron cryo-microscopy.
The enormous prevalence of tailed DNA bacteriophages on this planet is enabled by highly efficient self-assembly of hundreds of protein subunits into highly stable capsids. These capsids can stand with an internal pressure as high as ∼50 atmospheres as a result of the phage DNA-packaging process. Here we report the complete atomic model of the headful DNA-packaging bacteriophage Sf6 at 2.9 Å resolution determined by electron cryo-microscopy. The structure reveals the DNA-inflated, tensed state of a robust protein shell assembled via noncovalent interactions. Remarkable global conformational polymorphism of capsid proteins, a network formed by extended N arms, mortise-and-tenon-like intercapsomer joints, and abundant β-sheet-like mainchain:mainchain intermolecular interactions, confers significant strength yet also flexibility required for capsid assembly and DNA packaging. Differential formations of the hexon and penton are mediated by a drastic α-helix-to-β-strand structural transition. The assembly scheme revealed here may be common among tailed DNA phages and herpesviruses.


Existence of fatty acyl-CoA oxidizing system in (micro)peroxisomes of rabbit aorta.
A cyanide-insensitive palmitoyl-CoA oxidizing activity was detected in rabbit aorta. An assay developed for the arterial acyl-CoA oxidizing system was linear with respect to protein content of the homogenate between 12.5 and 100 micrograms and incubation time for at least 15 min. The system was shown to be localized in (micro)peroxisomes by centrifugation in sucrose density gradient. With a diet containing 1% (w/w) cholesterol and 3% (w/w) olive oil for 8 weeks the activity of peroxisomal beta-oxidation increased from 1.38 to 2.54 nmole/min/g aorta. These results show that the aortic catalase-positive particles have a capacity to oxidize fatty acyl-CoA and participate in fatty acid metabolism.


Metabolic control analysis of the Warburg-effect in proliferating vascular smooth muscle cells.
The accumulation and proliferation of vascular smooth muscle cells (VSMC) within the vessel wall is an important pathogenic feature in the development of atherosclerosis. Glucose metabolism has been implicated to play an important role in this cellular mechanism. To further elucidate the role of glucose metabolism in atherogenesis, glycolysis and its regulation have been investigated in proliferating VSMC. Platelet derived growth factor (PDGF BB)-induced proliferation of VSMCs significantly stimulated glucose flux through glycolysis. Further evaluating the enzymatic regulation of this pathway, the analysis of flux:metabolite co-responses revealed that anaerobic glycolytic flux is controlled at different sites of gycolysis in proliferating VSMCs, being consistent with the concept of multisite modulation. These findings indicate that regulation of glycolytic flux in proliferating VSMCs differs from traditional concepts of metabolic control of the Embden-Meyerhof pathway.


Effective treatment of advanced solid tumors by the combination of arsenic trioxide and L-buthionine-sulfoximine.
Clinical application of anticancer agents has been often hampered by toxicity against normal cells, so the achievement of their cancer-specific action is still one of the major challenges to be addressed. Previously, we reported that arsenic trioxide (As2O3) could be a promising new drug against not only leukemia but also solid tumors. The cytotoxicity of As2O3 occurred through the generation of reactive oxygen species (ROS), thus inhibiting radical scavenging systems would enhance the therapeutic efficacy of As2O3 provided that normal cells were relatively resistant to such a measure. Here, we report that the combination therapy of As2O3 with L-buthionine-sulfoximine (BSO), which inhibits a critical step in glutathione synthesis, effectively enhanced in vitro growth inhibition effect of As2O3 on all 11 investigated cell lines arising from prostate, breast, lung, colon, cervix, bladder, and kidney cancers, compared with As2O3 treatment alone. Furthermore, this combination enhanced cytotoxicity to cell lines from prostate cancer with less toxicity to those from normal prostate. In vitro cytotoxic assay using ROS-related compounds demonstrated that hydrogen peroxide (H2O2) is a major cytotoxic mediator among ROS molecules. Biochemical analysis showed that combined use of As2O3 and BSO blocked H2O2-scavenging systems including glutathione, catalase, and glutathione peroxidase, and that the degree of this blockade was well correlated with intracellular ROS levels and sensitivity to this treatment. Finally, the effectiveness of the combination therapy of As2O3 with BSO was demonstrated with an orthotopic model of prostate cancer metastasis. We propose that the combination therapy of As2O3 with BSO is a valid means of blockade of H2O2-scavenging system, and that the combination of a ROS-generating agent with an inhibitor of major scavenging systems is effective in terms of both efficacy and selectivity. Furthermore, because the effective doses of both compounds are within clinically achievable range, this report will lead to immediate benefit for the development of a new cancer therapy.


[Effect of naloxone on hypoalgesia in rats exposed to prolonged immobilization stress].
Significant hypoalgesia (tail-flick reflex at 60 degrees C) was observed in rats during the whole period of 24-hour immobilization in cramped cages, as compared to food-and-water deprived and control animals. This hypoalgesia was not antagonized by naloxone (1 mg/kg), however, the animals periodically receiving the drug during immobilization revealed aggressiveness and significant hypoalgesia after immobilization was discontinued (30-120 min observation).


Impact of Multiple Beams on the FLASH Effect in Soft Tissue and Skin in Mice.
FLASH proton pencil beam scanning (p-PBS) showed a reduction in mouse skin toxicity and fibrosis when delivered as a single, uninterrupted, high-dose fraction. Clinical p-PBS treatment usually requires multiple beams to achieve good conformality, and these beams are separated by minutes to allow patient and equipment repositioning. We evaluate the impact of multibeam versus single-beam proton radiation on the FLASH sparing effect on skin toxicity. The right hind leg of 10-week-old female C57Bl/6j mice was irradiated using a Varian ProBeam proton beam scanning gantry system at conventional (1 Gy/s) or FLASH (100 Gy/s) average field dose rate. We scored the skin toxicity after different doses for 7 weeks. The treatment was delivered as 1, 2, or 3 equal beams with an interruption of 2 minutes. For each beam delivery, the equipment remained in the same position so that there was a full overlap of beams administered. Single-beam delivery confirmed a benefit for p-PBS FLASH in this model at 30, 35, and 40 Gy. At 30 and 35 Gy, a single beam interruption of 2 minutes (2 × 15 Gy or 2 × 17.5 Gy) reduced the FLASH sparing effect, which remained significant (P < .001). However, 2 interruptions (3 × 10 Gy or 3 × 11.6 Gy) abrogated the normal tissue sparing effect. Our results indicate that the FLASH sparing effect in areas of beam overlap can be compromised by interruptions in delivery time. Time gap between overlapping beams and spatial arrangement of the delivered beams are important parameters for FLASH studies. The effect of multibeam needs to be studied on different organs of interest.


Pitfalls in diagnosis of interstitial pregnancy.
To determine the incidence and reasons for misdiagnosis in interstitial ectopic pregnancy. We conducted a retrospective study from 1990 to 2001. Women with interstitial pregnancy were identified and their case records retrieved and reviewed. Reasons for delay in diagnosis and associated morbidity were recorded. Thirty-six women were diagnosed as having interstitial pregnancy during the study period. Initial diagnosis was incorrect in 15 cases (41.7%). In 14 cases, the interstitial pregnancies were mistaken as intrauterine pregnancy. These misdiagnoses resulted in six inappropriate surgical procedures (evacuation of uterus) being performed and led to rupture of interstitial pregnancy in eight women. In two women, the interstitial pregnancy was mistaken as normal intrauterine pregnancy while the uterus itself was thought to be a cervical fibroid. In both cases, the interstitial pregnancies ruptured at 18-20 weeks of gestation. Despite advances in sonographic skills and equipment and the availability of beta-human chorionic gonadotropin (hCG) monitoring, misdiagnosis of interstitial pregnancy still occurs frequently. Clinicians should be aware of the limitations of various investigations and maintain a high index of suspicion.


Evaluation of food safety. National and international aspects.
Evaluation of the safety of chemicals in food have created considerable interest within the public, political, administrative, and scientific sectors in many parts o- the world. Political and administrative approaches may vary from country to country depdneing on traditions and cultural pattern. The political aims and goals of our times may be clearly defined, but they are often rather obscure seen from a scientific point of view. Health authorities are supposed to interpret the political intentions and transcribe them into practical administration. The use, by national and international health authorities, of the available scientific and technological knowledge to evaluate the safety of the food in question is discussed.


What do we know and what don't we know about tamoxifen in the human uterus.
Since its introduction in the early seventies, the list of indications for the use of the antiestrogen tamoxifen has been continuously expanded. Tamoxifen is now used for the treatment of metastatic breast cancer and for long-term and often indefinite administration as an adjuvant therapy. Large clinical trials in three countries are now evaluating the efficacy of tamoxifen as a preventive agent. However, tamoxifen therapy has been associated with an increased incidence of endometrial carcinoma. Laboratory and clinical data available to date on this controversial issue can be summarized as follows: a) Tamoxifen can have an estrogenic effect on endometrium in the presence of low estrogen levels. b) Tamoxifen treatment is probably associated with an increased incidence of endometrial cancer; however, this association appears to be linked to higher tamoxifen doses (40 mg/d). d) It is not known whether tamoxifen causes or allows the identification of occult endometrial carcinoma. e) At the present time there is evidence for a tumor promoting effect of tamoxifen on endometrial cancer at a dose of 20 mg per day. f) Replacement of tamoxifen by 'pure' antiestrogens or coadministration of progestins with tamoxifen do not appear to offer benefit unless clinical trials demonstrate a reduced incidence of endometrial problems. g) Patients must be evaluated for pre-existing endometrical carcinoma before starting tamoxifen therapy. f) Close followup of long-term tamoxifen patients with endometrial biopsies is recommended with individuals who experience symptoms.


Radiotherapy and radio-sensitization in H3K27M -mutated diffuse midline gliomas.
H3K27M mutated diffuse midline gliomas (DMGs) are extremely aggressive and the leading cause of cancer-related deaths in pediatric brain tumors with 5-year survival <1%. Radiotherapy is the only established adjuvant treatment of H3K27M DMGs; however, the radio-resistance is commonly observed. We summarized current understandings of the molecular responses of H3K27M DMGs to radiotherapy and provide crucial insights into current advances in radiosensitivity enhancement. Ionizing radiation (IR) can mainly inhibit tumor cell growth by inducing DNA damage regulated by the cell cycle checkpoints and DNA damage repair (DDR) system. In H3K27M DMGs, the aberrant genetic and epigenetic changes, stemness genotype, and epithelial-mesenchymal transition (EMT) disrupt the cell cycle checkpoints and DDR system by altering the associated regulatory signaling pathways, which leads to the development of radio-resistance. The advances in mechanisms of radio-resistance in H3K27M DMGs promote the potential targets to enhance the sensitivity to radiotherapy.


Basics of compounding: considerations for implementing United States pharmacopeia chapter 797 pharmaceutical compounding-sterile preparations, part 18: verification of automated compounding devices for parenteral nutrition compounding and finished preparation release checks and tests.
A sound quality-assurance program, which should include standard operating procedures, documentation, verification, and analytical and microbiological testing, is necessary to ensure the quality of compounded preparations. This article discusses in a practical matter verification of automated compounding devices for parenteral nutrition compounding and finished preparation release checks and tests, and provides practice clarification to the standards set forth by the United States Pharmacopeial Convention, Inc.


Awara (Astrocaryum vulgare M.) pulp oil: chemical characterization, and anti-inflammatory properties in a mice model of endotoxic shock and a rat model of pulmonary inflammation.
Awara (Astrocaryum vulgare M.) is a palm fruit mainly used in nutrition. We analysed the pulp oil for fatty acid, tocopherol, carotenoid, and phytosterol and we evaluated whether this oil may attenuate inflammation in vivo. In an endotoxic shock model, awara pulp oil treatment decreased pro-inflammatory cytokines and increased anti-inflammatory cytokines. In a pulmonary inflammation model, awara pulp oil treatment reduced eosinophil and lymphocyte numbers recovered into the broncho-alveolar lavages. These results suggest that awara pulp oil administration can efficiently counteract an acute and chronic inflammatory response in vivo that is probably mediated by fatty acids and minor compounds.


Postexercise syncope: evidence for increased activity of the sympathetic nervous system.
This report describes an association of postexertional syncope with increased levels of circulating catecholamines. A 36-year-old male who experienced postexercise bradycardia and asystole had higher basal plasma norepinephrine (120 versus 68 +/- 6 pg/ml) and epinephrine (18 versus less than 10 pg/ml) but a similar vagal tone (vagal tone index of 5.44 versus 5.81 +/- 1.00 U) when compared with 6 closely matched subjects who underwent an uneventful stress test.


Bone Marrow Adipocytes Contribute to Tumor Microenvironment-Driven Chemoresistance via Sequestration of Doxorubicin.
Chemoresistance is a significant problem in the effective treatment of bone metastasis. Adipocytes are a major stromal cell type in the bone marrow and may play a crucial role in developing microenvironment-driven chemoresistance. However, detailed investigation remains challenging due to the anatomical inaccessibility and intrinsic tissue complexity of the bone marrow microenvironment. In this study, we developed 2D and 3D in vitro models of bone marrow adipocytes to examine the mechanisms underlying adipocyte-induced chemoresistance. We first established a protocol for the rapid and robust differentiation of human bone marrow stromal cells (hBMSCs) into mature adipocytes in 2D tissue culture plastic using rosiglitazone (10 μM), a PPARγ agonist. Next, we created a 3D adipocyte culture model by inducing aggregation of hBMSCs and adipogenesis to create adipocyte spheroids in porous hydrogel scaffolds that mimic bone marrow sinusoids. Simulated chemotherapy treatment with doxorubicin (2.5 μM) demonstrated that mature adipocytes sequester doxorubicin in lipid droplets, resulting in reduced cytotoxicity. Lastly, we performed direct coculture of human multiple myeloma cells (MM1.S) with the established 3D adipocyte model in the presence of doxorubicin. This resulted in significantly accelerated multiple myeloma proliferation following doxorubicin treatment. Our findings suggest that the sequestration of hydrophobic chemotherapeutics by mature adipocytes represents a potent mechanism of bone marrow microenvironment-driven chemoresistance.


Glycine-bound NMDA receptors are stretch-activated.
In a recent study, Belin et al. demonstrated that glycine-bound NMDA receptors can be activated by mechanical forces in the absence of the neurotransmitter glutamate. The stretch-gated receptor exhibits biophysical properties similar to those of glutamate-gated receptors. These findings reveal that glycine-bound NMDA receptors could behave as mechanosensors in central nervous system (CNS) physiology.


Correction: Cardiovascular and Renal Outcomes of Renin-Angiotensin System Blockade in Adult Patients with Diabetes Mellitus: A Systematic Review with Network Meta-Analyses.
[This corrects the article DOI: 10.1371/journal.pmed.1001971.].


Anticonvulsant effects of ethanol stem bark extract of Lannea barteri (Anacardiaceae) in mice and chicks.
Preparation of Lannea barteri is used in the treatment of epilepsy, gastritis, childhood convulsions among other uses in northern Nigeria for many years. The popularity of its efficacy is well established among the Traditional Medical Practitioners. The present study aimed at screening the ethanol stem bark extract of Lannea barteri for possible anticonvulsant action. Anticonvulsant screening was carried out using pentylenetetrazole (PTZ), strychnine (STN) and picrotoxin (PTC) induced seizures in mice while Maximal electroshock (MES) test was carried out in day old chicks. Preliminary phytochemical screening of the extract was performed on the extract. The intraperitoneal median lethal dose (LD50) was carried out in mice. The intraperitoneal (i.p.) LD50 of the extract was estimated to be 567.70 mg/kg in mice. Lannea barteri (160 mg/kg) significantly (p ≤ 0.05) delayed the mean onset of seizures induced by PTZ when compared with normal saline treated group. Similarly, the extract at 160 mg/kg significantly (p ≤ 0.05) prolonged the latency of convulsion induced by STN. Lannea barteri (40 mg/kg) significantly (p ≤ 0.05) delayed the mean onset of seizures induced by picrotoxin in mice. The extracts at all the doses tested showed no observable effect in decreasing the mean recovery time of convulsed chicks in MEST. Flavonoids, alkaloids, tannins, saponins and glycosides were found present in the stem bark extract. Our findings revealed that the ethanol stem bark extract of Lannea barteri contained bioactive constituents that may be useful in the management of petit mal epilepsy and supports the ethnomedical claim for the use of its stem bark in the management of epilepsy.


Luteolin Protects Against CIRI, Potentially via Regulation of the SIRT3/AMPK/mTOR Signaling Pathway.
Mitochondrial abnormalities accelerate the progression of ischemic brain damage. Sirtuin 3 (SIRT3) is mainly found in mitochondria and affects almost all major aspects of mitochondrial function. Luteolin, a flavonoid with diverse biological properties, including antioxidant activity, inhibition of cell apoptosis and regulation of autophagy. It also modulates the activity of AMP activated kinase and/or sirtuin 1 (SIRT 1) by regulating the expression of sirtuins. We investigated the protective effects of luteolin on cerebral ischemia-reperfusion. It was found through experiments that luteolin reduced the infarcted area of MCAO rat model, and based on the experimental results, it was inferred that luteolin affected the AMPK, mTOR and SIRT3 pathways, thereby protecting brain cells. As expected, we found that luteolin can reduce the neurological function score, the degree of cerebral edema, the cerebral infarction volume, alleviate morphological changes in the cortex and hippocampus, increase neuron survival and decrease the number of apoptotic neurons. At the same time, luteolin significantly reduced the number of GFAP and Iba-1 positive glial cells in the hippocampus while enhanced the scavenging of oxygen free radicals and the activity of SOD in mitochondria. Addtionally, it can also enhance antioxidant capacity via the reversal of mitochondrial swelling and the mitochondrial transmembrane potential. Moreover, luteolin can increase SIRT3-targeted expression in mitochondria, decrease the phosphorylation of AMPK, and increase phosphor-mTOR (p-mTOR) levels, which may have occurred specifically through activation of the SIRT3/AMPK/mTOR pathway. We speculate that luteolin reduces the pathological progression of CIRI by increasing SIRT3 expression and enhancing mitochondrial function. Therefore, the results indicate that luteolin can increase the transduction of SIRT3, providing a potential mechanism for neuroprotective effects in patients with cerebral ischemia.


Readability, understandability and language accessibility of Swedish websites about the coronavirus disease 2019: a cross-sectional study.
The COVID-19 pandemic has caused significant morbidity and mortality. To mitigate its spread, members in the general population were prompted to apply significant behavioral changes. This required an effective dissemination of understandable information accessible for people with a wide range of literacy backgrounds. The aim of this study was to investigate the readability, understandability and language accessibility of Swedish consumer-oriented websites containing information about COVID-19. Websites were identified through systematic searches in Google.se (n = 76), and were collected in May 2020 when the pandemic spread started in Sweden. Readability and understandability were assessed with the Readability Index, the Ensuring Quality Information for Patients (EQIP) tool, and the Patient Education Materials Assessment Tool Understandability subscale (PEMAT-PU). The median total sample score for Readability Index was 42.0, with the majority of scores being classified as moderate (n = 30, 39%) or difficult (n = 43, 57%). Median total sample scores were for EQIP 54.0% (IQR = 17.0, Range = 8-75) and for PEMAT-PU 60.0% (IQR = 14.75, Range = 12-87). The majority of the websites did not have any texts or links containing information in an alternative language (n = 58, 76%). Swedish websites contained information of difficult readability and understandability at the beginning of the coronavirus disease 2019 pandemic, with few providing information available in alternative languages. It is possible that these deficits contributed to the spread and impact of the virus. There is a need for studies investigating methods aiming to enhance the readability, understandability and language accessibility of web-based information at the beginning of an epidemic or pandemic.


A multicellular 3D heterospheroid model of liver tumor and stromal cells in collagen gel for anti-cancer drug testing.
Two-dimensional (2D) monolayer cultures are the standard in vitro model for cancer research. However, they fail to recapitulate the three-dimensional (3D) environment and quickly lose their function. In this study, we developed a new 3D multicellular heterospheroid tumor model in a collagen hydrogel culture system that more closely mimics the in vivo tumor microenvironment for anti-cancer drug testing. Three aspects of cancer were chosen to be modeled based on their ability to resist anti-cancer drugs: 3D, multicellularity, and extracellular matrix (ECM) barrier. The hanging drop method and co-culture of liver carcinoma with stromal fibroblasts were used to form controlled and uniform heterospheroids. These heterospheroids were then encapsulated in collagen gel in order to create a 3D model of liver cancer that would act more similarly to in vivo ECM conditions. The 3D heterospheroid tumor model was tested with an anti-cancer drug to determine how each of the above aspects affects drug resistance. The results demonstrate that the 3D heterospheroid model is more resistant to drug over 2D monolayer and homospheroid cultures, indicating stromal fibroblasts and collagen hydrogel culture system provides more resistance to anti-cancer drug. This study will provide useful information toward the development of improved biomimetic tumor models in vitro for cancer research in pre-clinical drug development.


[Epidermoid thymoma--a variety of thymus gland cancer].
Epidermoid thymoma was referred to thymal malignancies after an evaluation of the data on its clinical course and microscopic structure. This tumor may be diagnosed preoperatively on the basis of an analysis of clinico-roentgeno-endoscopic data and findings of a cytological, histological and electron-microscopic examinations.


Why does a sucrose choice reduce the consumption of alcohol in C57BL/6J mice?
To determine why animals reject alcohol when offered palatable solutions of sucrose, male C57BL/6J mice were challenged first with 5% sucrose then with 10% sucrose, while given continuous free-access to alcohol and water. The 5% sucrose dramatically reduced the intake of alcohol and increased the intake of total fluid by an average of 7.3 ml/day. The suppression of alcohol intake could not be attributed to a volumetric ceiling since access to 10% sucrose produced a further large increase in total intake (8.8 ml/day). The results support the interpretation that animals consume alcohol for characteristics it shares with sucrose.


Proteomic responses of drought-tolerant and drought-sensitive cotton varieties to drought stress.
Drought, one of the most widespread factors reducing agricultural crop productivity, affects biological processes such as development, architecture, flowering and senescence. Although protein analysis techniques and genome sequencing have made facilitated the proteomic study of cotton, information on genetic differences associated with proteomic changes in response to drought between different cotton genotypes is lacking. To determine the effects of drought stress on cotton seedlings, we used two-dimensional polyacrylamide gel electrophoresis (2-DE) and matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry to comparatively analyze proteome of drought-responsive proteins during the seedling stage in two cotton (Gossypium hirsutum L.) cultivars, drought-tolerant KK1543 and drought-sensitive Xinluzao26. A total of 110 protein spots were detected on 2-DE maps, of which 56 were identified by MALDI-TOF and MALDI-TOF/TOF mass spectrometry. The identified proteins were mainly associated with metabolism (46.4 %), antioxidants (14.2 %), and transport and cellular structure (23.2 %). Some key proteins had significantly different expression patterns between the two genotypes. In particular, 5-methyltetrahydropteroyltriglutamate-homocysteine methyltransferase, UDP-D-glucose pyrophosphorylase and ascorbate peroxidase were up-regulated in KK1543 compared with Xinluzao26. Under drought stress conditions, the vacuolar H(+)-ATPase catalytic subunit, a 14-3-3g protein, translation initiation factor 5A and pathogenesis-related protein 10 were up-regulated in KK1543, whereas ribosomal protein S12, actin, cytosolic copper/zinc superoxide dismutase, protein disulfide isomerase, S-adenosylmethionine synthase and cysteine synthase were down-regulated in Xinluzao26. This work represents the first characterization of proteomic changes that occur in response to drought in roots of cotton plants. These differentially expressed proteins may be related to biochemical pathways responsible for drought tolerance in KK1543. Although further studies are needed, this proteomic analysis underlines the role of post-translational events. The differentially expressed proteins and their corresponding genes may be used as markers for the breeding of drought tolerance in cotton.


Risk and early predictive factors of anastomotic leakage in laparoscopic low anterior resection for rectal cancer.
In recent years, laparoscopic surgery has been widely used for rectal cancer. In laparoscopic rectal surgery, a double-stapling technique (DST) anastomosis using a stapling device is considered a relatively difficult procedure. Postoperative anastomotic leakage (AL) is a major complication related to patients' quality of life and prognosis. This study was a retrospective, single-institution study of 101 rectal cancer patients who underwent laparoscopic low anterior resection (LAR) with DST anastomosis (excluding simultaneous resection of other organs and construction of protective diverting stoma) between February 2008 and November 2017 at the Gifu University Graduate School of Medicine. This study aimed to identify risk and early predictive factors of AL. Among 101 patients, symptomatic AL occurred in 13 patients (12.9%), of whom 10 were male and 3 were female. Their median BMI was 22.7 kg/m2 (range, 17.9-26.4 kg/m2). Among the pre- and intraoperative factors, AL was significantly associated with tumor location (lower rectum), distance from the anal verge (< 6 cm), intraoperative blood loss (≥ 50 ml), and the number of linear staples (≥ 2) in univariate analysis. In multivariate analysis, only intraoperative blood loss (≥ 50 ml, odds ratio [OR] 4.59; 95% confidence interval [CI] 1.04-19.52; p = 0.045) was identified as an independent risk factor for AL. Among the postoperative factors, AL was significantly associated with tachycardia-POD1 (≥ 100 bpm), CRP-POD3 (≥ 15 mg/dl), fever on postoperative day (fever-POD) 3 (≥ 38 °C), and first defecation day after surgery (< POD3) in univariate analysis. In multivariate analysis, fever-POD3 (≥ 38 °C, OR 30.97; 95% CI 4.68-311.22; p = 0.0003) and first defecation day after surgery (< POD3, OR 5.82; 95% CI 1.34-31.30; p = 0.019) were identified as early predictive factors for AL. In this study, intraoperative blood loss was an indicator of difficulty in a transection and anastomosing procedure, and fever-POD3 and early first defecation day after surgery were independent early predictive factors for AL. Careful surgery using an appropriate technique and standardized procedures with minimal bleeding and careful postoperative management paying attention to fever and defecation may prevent the onset and severity of AL.


Perceived stigma of purchasing sex among Latino and non-Latino male clients of female sex workers in Tijuana, Mexico.
HIV prevention efforts must be comprehensive in their understanding of the factors involved in HIV risk. Male clients, who have received less research attention than female sex workers (FSWs), may experience stigma as a function of purchasing sex. Perceived stigma may be related to poor psychological outcomes, risky psychosexual characteristics, and higher drug and sexual risk behavior among male clients of FSWs. However, perceived stigma of purchasing sex may differ between clients of different ethnic groups. In the present study, we examine the correlates of perceived stigma of purchasing sex among Latino versus non-Latino male clients of FSWs in Tijuana, Mexico. Using time-location sampling, we recruited 375 male clients (323 Latino, 52 non-Latino) in Tijuana who completed a computerized survey on various measures. We measured perceived stigma of purchasing sex using three items we developed for this study. Using linear regression analyses we found that perceived stigma was associated with greater guilt, a greater feeling of escape from everyday life, and more negative condom attitudes among Latino clients. This was not found among non-Latino clients. Features of Latino culture, like machismo, and how they may relate to stigma of purchasing sex are discussed.


Doubly linked chiral phenanthrene oligomers for homogeneously π-extended helicenes with large effective conjugation length.
Helically twisted conductive nanocarbon materials are applicable to optoelectronic and electromagnetic molecular devices working on the nanometer scale. Herein, we report the synthesis of per-peri-perbenzo[5]- and [9]helicenes in addition to previously reported π-extended [7]helicene. The homogeneously π-extended helicenes can be regarded as helically fused oligo-phenanthrenes. The HOMO-LUMO gap decreased significantly from 2.14 to 1.15 eV with increasing helical length, suggesting the large effective conjugation length (ECL) of the π-extended helical framework. The large ECL of π-extended helicenes is attributed to the large orbital interactions between the phenanthrene subunits at the 9- and 10-positions, which form a polyene-like electronic structure. Based on the experimental results and DFT calculations, the ultrafast decay dynamics on the sub-picosecond timescale were attributed to the low-lying conical intersection.


Structure, function and regulation of the vacuolar (H+)-ATPases.
The vacuolar (H+)-ATPases (or V-ATPases) function to acidify intracellular compartments in eukaryotic cells, playing an important role in such processes as receptor-mediated endocytosis, intracellular membrane traffic, protein degradation and coupled transport. V-ATPases in the plasma membrane of specialized cells also function in renal acidification, bone resorption and cytosolic pH maintenance. The V-ATPases are composed of two domains. The V1 domain is a 570-kDa peripheral complex composed of 8 subunits (subunits A-H) of molecular weight 70-13 kDa which is responsible for ATP hydrolysis. The V0 domain is a 260-kDa integral complex composed of 5 subunits (subunits a-d) which is responsible for proton translocation. The V-ATPases are structurally related to the F-ATPases which function in ATP synthesis. Biochemical and mutational studies have begun to reveal the function of individual subunits and residues in V-ATPase activity. A central question in this field is the mechanism of regulation of vacuolar acidification in vivo. Evidence has been obtained suggesting a number of possible mechanisms of regulating V-ATPase activity, including reversible dissociation of V1 and V0 domains, disulfide bond formation at the catalytic site and differential targeting of V-ATPases. Control of anion conductance may also function to regulate vacuolar pH. Because of the diversity of functions of V-ATPases, cells most likely employ multiple mechanisms for controlling their activity.


A gel-free 3D microfluidic cell culture system.
3D microfluidic cell culture systems offer a biologically relevant model to conduct micro-scale mammalian cell-based research and applications. Various natural and synthetic hydrogels have been successfully incorporated into microfluidic systems to support mammalian cells in 3D. However, embedment of cells in hydrogels introduces operational complexity, potentially hinders mass transfer, and is not suitable for establishing cell-dense, ECM-poor constructs. We present here a gel-free method for seeding and culturing mammalian cells three-dimensionally in a microfluidic channel. A combination of transient inter-cellular polymeric linker and micro-fabricated pillar arrays was used for the in situ formation and immobilization of 3D multi-cellular aggregates in a microfluidic channel. 3D cellular constructs formed this way are relieved of hydrogel embedment for cellular support. Two mammalian cell lines (A549 and C3A) and a primary mammalian cell (bone marrow mesenchymal stem cells) were cultured in the gel-free 3D microfluidic cell culture system. The cells displayed 3D cellular morphology, cellular functions and differentiation capability, affirming the versatility of the system as a 3D cell perfusion culture platform for anchorage-dependent mammalian cells.