Genome-wide methylome analysis of two strains belonging to the hypervirulent Neisseria meningitidis serogroup W ST-11 clonal complex.
A rising incidence of meningococcal serogroup W disease has been evident in many countries worldwide. Serogroup W isolates belonging to the sequence type (ST)-11 clonal complex have been associated with atypical symptoms and increased case fatality rates. The continued expansion of this clonal complex in the later part of the 2010s has been largely due to a shift from the so-called original UK strain to the 2013 strain. Here we used single-molecule real-time (SMRT) sequencing to determine the methylomes of the two major serogroup W strains belonging to ST-11 clonal complex. Five methylated motifs were identified in this study, and three of the motifs, namely 5'-GATC-3', 5'-GAAGG-3', 5'-GCGCGC-3', were found in all 13 isolates investigated. The results showed no strain-specific motifs or difference in active restriction modification systems between the two strains. Two phase variable methylases were identified and the enrichment or depletion of the methylation motifs generated by these methylases varied between the two strains. Results from this work give further insight into the low diversity of methylomes in highly related strains and encourage further research to decipher the role of regions with under- or overrepresented methylation motifs.


A deletion in the Hermansky-Pudlak syndrome 4 (Hps4) gene appears to be responsible for albinism in channel catfish.
Albinism is caused by a series of genetic abnormalities leading to reduction of melanin production. Albinism is quite frequent in catfish, but the causative gene and the molecular basis were unknown. In this study, we conducted a genome-wide association study (GWAS) using the 250 K SNP array. The GWAS analysis allowed mapping of the albino phenotype in the Hermansky-Pudlak syndrome 4 (Hps4) gene, which is known to be involved in melanosome biosynthesis. Sequencing analysis revealed that a 99-bp deletion was present in all analyzed albino catfish at the intron 2 and exon 3 junction. This deletion led to the skipping of the entire exon 3 which was confirmed by RT-PCR. Therefore, Hps4 was determined to be the candidate gene of the catfish albinism.


The bs-YHEDA peptide protects the brains of senile mice and thus recovers intelligence by reducing iron and free radicals.
Iron accumulates in the brain with age and catalyzes free radical damage to neurons, thus playing a pathogenic role in Alzheimer's disease (AD). To decrease the incidence of AD, we synthesized the iron-affinitive peptide 5YHEDA to scavenge the excess iron in the senile brain. However, the blood-brain barrier (BBB) blocks the entrance of macromolecules into the brain, thus decreasing the therapeutic effects. To facilitate the entrance of the 5YHEDA peptide, we linked the low-density lipoprotein receptor (LDLR)-binding segment of ApoB-100 to 5YHEDA (named "bs-YHEDA"). The results of intravenous injections of bs-5YHEDA into senescent mice demonstrated that bs-YHEDA entered the brain, increased ferriportin levels, reduced iron and free radical levels, decreased the consequences of neuronal necrosis and ameliorated cognitive disfunction without kidney or liver damage. bs-5YHEDA is a safe iron and free radical remover that potentially alleviates aging and Alzheimer's disease.


Biomass allocation and seasonal non-structural carbohydrate dynamics do not explain the success of tall forbs in short alpine grassland.
The majority of alpine plants are of small stature. Through their small size alpine plants are decoupled from the free atmospheric circulation and accumulate solar heat. However, a few alpine species do not follow that "rule" and protrude with their aboveground structures from the microclimatic shelter of the main canopy boundary layer. We aim at explaining the phenomenon of being tall by exploring the biomass production and carbon relations of four pairs of small and tall phylogenetically related taxa in alpine grassland. We compared species and stature-specific biomass allocation, shifts in non-structural carbohydrate (NSC) concentrations in different tissues throughout the season, and we used 13C labels to track carbon transfer from leaves to belowground structures. Small and tall herbs did not differ in their above- to belowground biomass allocation. The NSC composition (starch, fructan, simple sugars) and allocation did not show a stature-specific pattern, except for higher concentrations of simple sugars in tall species during their extended shoot growth. In relative terms, tall species had higher NSC pools in rhizomes, whereas small species had higher NSC pools in roots. Our findings do not place tall alpine forbs in an exceptional category in terms of biomass allocation and carbohydrate storage. The tall versus small stature of the examined herbs does not seem to be associated with specific adjustments in carbon relations. 13C pulse labelling revealed early C autonomy in young, unfolding leaves of the tall species, which are thus independent of the carbon reserves in the massive belowground organs.


Clinicians' reported use of clinical priority assessment criteria and their attitudes to prioritization for elective surgery: a cross-sectional survey.
To explore the attitudes of clinicians working in New Zealand publicly funded hospitals towards prioritizing patients for elective surgery, and their reported use of clinical priority assessment criteria (CPAC). A cross-sectional study using a postal questionnaire. The questionnaire drew on themes identified from an earlier qualitative study. Questions were closed and information was sought about perceptions of the need to prioritize patients, effective ways of doing so and the use of CPAC. New Zealand. A national sample of cardiologists, cardiac, general and orthopaedic surgeons, and registrars. Three hundred and thirty-two clinicians responded to the survey (74.1%). Respondents generally agreed that a nationally consistent method of prioritizing patients for surgery was required but felt their clinical judgement was the most effective way of prioritizing patients. Current CPAC were considered to be administrative tools and there was marked variation in their reported use. Consistent use of CPAC using the constructs provided was more likely to be reported by cardiac specialists than general or orthopaedic surgeons. Other features of the hospital system in which surgeons worked also had a major impact on access to elective surgery. Clinicians recognized the need for a nationally consistent method of prioritizing patients. Although most did not consider current CPAC were effective in achieving this, many felt there was some potential in further development of tools. However, further development is problematic in the absence of objective measures of need and ability to benefit.


Electron microscopy of meiosis in Drosophila melanogaster females. I. Structure, arrangement, and temporal change of the synaptonemal complex in wild-type.
Complete reconstruction of the synaptonemal complex in 12 pachytene (defined here as that stage in which the synaptonemal complex is continuous throughout the bivalents) nuclei from one wild-type germarium has permitted the following observations. 1) Drosophila melanogaster bivalents at pachytene exhibit a chromocentral arrangement; the pericentric heterochromatin of all bivalents lies in one region of the nucleus, the chromocenter. Telomeric ends do not appear to abutt the nuclear envelope. 2) Synaptonemal complex is present in the pericentric heterochromatin; however, it is morphologically distinct from that present in the euchromatic portion of thesynaptonemal complex of the bivalent arms is greatest at early pachytene; the synaptonemal complex then becomes progressively shorter. Minimum length is approximately one-half of the maximum. 4) Decrease in length of synaptonemal complex is accompanied by an increase in thickness. Reconstruction of 20 pachytene nuclei from an additional 8 germaria suggests that these observations are typical. Correlations between these cytological observations and genetic observations (e.g., patterns of crossing-over) are discussed.


Synthesis and biodistribution of [18F]-5-fluorocytosine.
[18F]-5-fluorocytosine was prepared by reaction of [18F]-acetylhypofluorite with cytosine in acetic acid and was isolated in an overall radiochemical yield of 20%. Tissue distribution studies in sarcoma-bearing rats indicated in vivo stability, limited tissue uptake and rapid urinary excretion.


Barucainide, a novel class Ib antiarrhythmic agent with a slow kinetic property: electrophysiologic observations in isolated canine and rabbit cardiac muscle.
Electrophysiologic effects of barucainide hydrochloride on the transmembrane potentials of isolated canine and rabbit cardiac muscle were investigated by means of a standard microelectrode technique. Barucainide (10(-6) to 3.0 x 10(-5) mol/L) produced concentration-dependent inhibition of the maximum upstroke velocity (Vmax) in canine Purkinje fibers and ventricular muscle. Tonic block of Vmax was small and negligible. Barucainide produced marked use-dependent block (UDB). The onset rate of UDB and the speed of recovery from UDB were comparable to those of disopyramide. The recovery time constant was 8.0 +/- 0.8 seconds. Membrane depolarization induced by high concentrations of potassium enhanced the inhibitory action of barucainide on Vmax. The enhancement of tonic block was much greater than that of UDB indicating a selective effectiveness of the drug in pathologically depolarized tissues. Barucainide produced marked shortening of the action potential duration (APD), which indicates that barucainide exerts class Ib antiarrhythmic effects. Such shortening effects on the APD were not affected by pretreatment with 1 mmol/L cobalt or with 0.5 mmol/L 4-aminopyridine. In contrast, barucainide had no marked effects on the APD in the presence of 4.0 x 10(-5) mol/L lidocaine, although it produced almost the same extent of Vmax inhibition as did barucainide alone. Frequency of the pacemaker activity in the rabbit sinoatrial tissue and of the automaticity at normal resting potential in Purkinje fibers enhanced by 2.0 X 10(-6) mol/L isoproterenol were significantly suppressed by barucainide. However, barucainide up to 3.0 x 10(-5) mol/L failed to suppress the firing frequency of the abnormal automaticity in canine Purkinje fibers induced by 5 mmol/L barium. These overall findings indicate that barucainide is a novel class Ib antiarrhythmic agent which, unlike other Ib agents, has a slow kinetic property. However, the precise significance of this unique electrophysiologic feature with respect to the antiarrhythmic action of the drug is not known but provides the basis for understanding the relationship of electrophysiologic effects of barucainide in vitro and its potential antiarrhythmic actions in experimental animals and in humans.


Anion Donicity of Liquid Electrolytes for Lithium Carbon Fluoride Batteries.
The increasing demand for high-energy powers have greatly incentivized the development of lithium carbon fluoride (Li||CFx ) cells. Five kinds of non-aqueous liquid electrolytes with various kinds of lithium salts (LiX, X=PF6 - , TFSI- , BF4 - , ClO4 - , and CF3 SO3 - ) were comparatively studied. Intriguingly, the LiBF4 -based electrolyte show relatively moderate ionic conductivities; yet, the corresponding Li||CFx cells deliver the highest discharge capacities among them. A combination of morphological and compositional analyses of the discharge CFx cathode suggest that the moderate donicity of BF4 - anion is accountable for favoring the breakdown of C-F bonds, and subsequently forming crystalline lithium fluoride as the main discharge products. This work brings not only fresh understanding on the role of salt anions for Li||CFx cells, but also inspire the electrolyte design for other conversion-type (sulfur and/or organosulfur) cathode materials desired for high-energy applications.


Impedance cardiography: a bridge between research and clinical practice in the treatment of heart failure.
This paper proposes that impedance cardiography could narrow the gap between heart failure clinical research and the appropriate and timely application of new knowledge and technology in the care of patients with heart failure. Research variables and measurement strategies, identified in the heart failure scientific literature between 1994-1999, are compared to measures that can be obtained through a cost effective, noninvasive technology--impedance cardiography. Emphasis is placed on case reports that illustrate how "real time" evaluation and trending of key hemodynamic variables through impedance cardiography monitoring has been used to apply state of the science knowledge and technology to improve the inpatient and outpatient management of care for patients with severe heart failure. (c)2000 by CHF, Inc.


The role of plant species on runoff and soil erosion in a Mediterranean shrubland.
Shrubland is a Mediterranean biome characterized by densely growing evergreen shrubs adapted to fire events. To date, scientific research has focused on the impact of vegetation on soil erosion mainly through the control that plant biomass or plant cover exerts on sediment delivery and runoff discharge, being the individual plant species influence on hydrological and erosional processes not achieved in detail. The objective of this research is to determine: i) runoff and soil losses in a shrubland-covered rangeland at Sierra de Enguera, Spain; and ii) how four plant species affect soil and water losses. We measured soil cover, soil properties, runoff discharge and sediment yield under natural rainfall for five years (2010-2014) in a typical shrubland burnt in 1999. Four plant species were selected with 4 plots each: Ulex parviflorus Pourr., Pistacia lentiscus L., Quercus coccifera L. and Rosmarinus officinalis L. Despite that the soil properties and plant cover did not exhibit statistically significant differences among plant species, the runoff discharge was lower on Q. coccifera (4.87%, SE 0.24) and P. lentiscus (6.24%, SE 0.51) than on U. parviflorus (13.41%, SE 0.58) and R. officinalis (13.84%, SE 1.23). Sediment concentrations were, respectively, 3.91, 4.33, 4.31 and 4.88 g l-1, and the differences between R. officinalis and the other species were statistically significant. The runoff discharge determined differences in soil erosion rates among the plant species with lower rates on P. lentiscus (1.36 Mg ha-1 y-1) and Q. coccifera (1.53 Mg ha-1 y-1), than on U. parviflorus (3.17 Mg ha-1 y-1) and R. officinalis (3.85 Mg ha-1 y-1). This long term in situ study indicated that Q. coccifera and P. lentiscus are more efficient in controlling runoff discharge and soil losses than U. parviflorus and R. officinalis one decade after a fire. We discuss these results in light of the recent findings by the scientific community of the role of the canopy cover (rainfall interception), soil macropore and root system, and the water repellency that control the hydrological response of the soil (e.g. runoff generation, infiltration). The information supplied by 5 years of research is relevant for restoration and rehabilitation programs and advise that Q. coccifera and P. lentiscus are the most efficient plant species to control soil and water losses within the Mediterranean shrubland. This is an applied science approach for a better management of rangelands.


Ketamine anesthesia in pediatric ophthalmic office procedures (October 1985-October 1986).
We describe a prospective study of 18 pediatric ophthalmic patients given low-dose intramuscular ketamine hydrochloride as the sole or adjunct anesthetic agent. Our results indicated that there was a low incidence of side effects with successful operative outcomes.


Mitochondrial uncoupling and the isodynamic equivalents of protein, fat and carbohydrate at the level of biochemical energy provision.
The effects of uncoupling of mitochondrial oxidative phosphorylation on the efficiency of energy conservation during oxidation of amino acids, fatty acids, glycerol, glucose and 101 food proteins have been examined in order to compare how uncoupling at coupling site 1 affects energy yields compared with uncoupling at sites 2 + 3 and uncoupling by proton leakage. The effects of uncoupling by each mechanism on the isodynamic equivalents of carbohydrate, fat and protein at the level of cytoplasmic ATP yield have been estimated. Energy conservation during amino acid oxidation decreased relative to that for glucose as uncoupling by all three mechanisms increases. This effect is least when uncoupling is at site 1 and is associated with a fall in the isodynamic equivalent for protein:glucose of 4% maximally, and a fall in the cytoplasmic ATP yield for glucose of 25% (15-30%) when accounting for uncertainty in the choice of proton stoichiometries). Variation in the efficiency of energy conservation for the different amino acids is large for both highly coupled and uncoupled mitochondria but the range of efficiencies for the oxidation of 101 food proteins is relatively small (less than 6% of the mean) for a tightly coupled system. This range increases absolutely (minimally fourfold) and relatively (minimally 44% of the mean value) with severely uncoupled mitochondria but is nearly constant (changes by less than 1% relative to the mean) within the probable physiologically relevant range of uncoupling in the whole body and in the full range of uncoupling at site 1.(ABSTRACT TRUNCATED AT 250 WORDS)


Comparison of hemolytic activities of coal fly ash and its soluble and insoluble fractions.
Coal fly ash of a particle diameter smaller than 10 micron was collected from the precipitator of a power plant in Hong Kong. Comparison of hemolytic activities between fly ash and free silica showed that fly ash had a lower biological effect than free silica. The hemolytic activities of the soluble and insoluble fractions of fly ash were further compared by two methods: total hemoglobin method and cyanmethemoglobin method. An analysis of results showed significant differences for fly ash and its soluble fraction between methods (P less than 0.05 and P less than 0.01, respectively). Fly ash, which contained a silicate level similar to its insoluble fraction, had a hemolytic activity higher than the summation of both its soluble and insoluble fractions. This indicates that the hemolytic activity was independent of the silicate content in the fly ash samples.


The impact of inactive infants on clinic-based immunization rates.
Clinic-based immunization rates are used to evaluate clinic performance and immunization interventions, but they typically exclude so-called inactive patients (ie, those who no longer receive care at the clinic). We assessed the effect of enhanced ascertainment of inactive patients on clinic-based immunization rates and on the conclusions of a randomized controlled trial. The study was a post hoc analysis of a cluster-randomized controlled trial. Infant randomization to the immunization intervention (4 clinics) or control group (4 clinics) was based on the site of their 2-week well-child care visit. The study was conducted at an integrated inner-city health care system serving a low-income population. A total of 2190 infants born between July 1, 1998, and June 30, 1999, who attended at least 1 postnatal visit, participated. In control sites, clinic staff documented inactive infants in the immunization registry and medical charts. The research staff undertook additional patient tracking efforts in the intervention clinics. Control clinics identified 155 (13.4%) of 1160 children as inactive within 1 year of birth, whereas 284 (27.6%) of 1030 intervention infants were documented as inactive (P < .001). In bivariate analyses from the randomized trial, immunization rates differed between intervention and control branches. In multivariate models, immunization rates were significantly higher in the intervention branch when inactive infants were removed (adjusted relative risk 1.58; 95% confidence interval, 1.28-1.89), but not when they were included (adjusted relative risk 1.09; 95% confidence interval, 0.97-1.21). Additional patient tracking efforts can dramatically influence inactive patient documentation and clinic-based immunization rates used for various purposes.


Gas chromatographic assay with pharmacokinetic applications for monitoring T-2 and HT-2 toxins in plasma.
A gas-liquid chromatographic (GLC) method for monitoring T-2 and HT-2 toxins in plasma was developed. The procedure involved extraction of the toxins with ethyl acetate, chromatography on a C18 reversed-phase column and derivatization with heptafluorobutyric anhydride (HFBA). The T-2 and HT-2 HFBA derivatives were chromatographed on OV-17 at various temperatures and measured with an electron-capture detector. Iso-T-2 toxin and iso-HT-2 toxin were used as internal standards. Recoveries averaged 95.1 +/- 8.6% for T-2 toxin and 102.1 +/- 5.2% for HT-2 toxin at levels ranging from 40 to 120 ng/ml. The limits of detection were 30 and 5 ng/ml of T-2 and HT-2 toxin, respectively. The range of the assay covers plasma concentrations at which toxicity becomes manifest. The pharmacokinetic application of this GLC method is illustrated by simultaneous monitoring of T-2 and HT-2 toxins levels in plasma obtained after intravenous administration of T-2 toxin to a dog.


Breast self-examination and extent of disease: a population-based study.
A population-based, case-control study was conducted to examine whether infrequent breast self-examination (BSE) is associated with the detection of breast cancer at a later stage of disease. A group of 435 women with newly diagnosed, regional or distant breast carcinoma from Connecticut were interviewed and compared with 887 age-frequency-matched women without breast cancer. A case-control method eliminates lead time bias that may have been present in prior studies that evaluated BSE efficacy. Cases were found to have practiced monthly BSE more frequently than controls (27 vs. 21%). No differences in frequency of BSE was found between cases and controls after controlling for the potentially confounding effects of breast cancer risk factors and mammography (OR = 1.26; 95% CI, 0.77 to 2.07).


Ventral Tegmental Area Microinjected-SKF38393 Increases Regular Chow Intake in 18 Hours Food-Deprived Rats.
Ventral Tegmental Area (VTA) dopamine neurons play an important role in reward mechanisms of food intake, and VTA dopamine receptors exist on the terminal of glutamatergic and GABAergic neurons and regulate Gamma-Aminobutyric Acid (GABA) and glutamate release. To our knowledge, no evidence indicates any role for VTA D1 dopamine receptors in regular chow intake. In this paper, different dose of SKF38393, a D1 receptor agonist, was microinjected in VTA of 18-h food deprived-conscious rats and food intake was measured. Our results revealed that VTAmicroinjected SKF383993 increased regular chow intake in a dose-dependent manner. The SKF3833 stimulatory effect persisted over 2 h post-injection. The results showed that the SKF38393, at doses less than 5 μg, did not affect locomotor activities. VTA D1-like and/or serotonergic receptors may be involved in regulatory pathways. the current study suggests that VTA D1-like and/or serotonergic receptors not only affects food reward but is also involved in regulatory mechanisms of regular feeding.


Diagnostic accuracy of narrow-band imaging endoscopy with targeted biopsies compared with standard endoscopy with random biopsies in patients with Barrett's esophagus: A systematic review and meta-analysis.
Endoscopic surveillance for dysplasia in Barrett's esophagus (BE) with random biopsies is the primary diagnostic tool for monitoring clinical progression into esophageal adenocarcinoma. As an alternative, narrow-band imaging (NBI) endoscopy offers targeted biopsies that can improve dysplasia detection. This study aimed to evaluate NBI-guided targeted biopsies' diagnostic accuracy for detecting dysplasia in patients undergoing endoscopic BE surveillance compared with the widely used Seattle protocol. Cochrane DTA Register, MEDLINE/PubMed, EMBASE, OpenGrey, and bibliographies of identified papers were searched until 2018. Two independent investigators resolved discrepancies by consensus, study selection, data extraction, and quality assessment. Data on sensitivity, specificity, and predictive values were pooled and analyzed using a random-effects model. Of 9528 identified articles, six studies comprising 493 participants were eligible for quantitative synthesis. NBI-targeted biopsy showed high diagnostic accuracy in detection of dysplasia in BE with a sensitivity of 76% (95% confidence interval [CI]: 0.61-0.91), specificity of 99% (95% CI: 0.99-1.00), positive predictive value of 97% (95% CI: 0.96-0.99), and negative predictive value of 84% (95% CI: 0.69-0.99) for detection of all grades of dysplasia. The receiver-operating characteristic curve for NBI model performance was 0.8550 for detecting all dysplasia. Narrow-band imaging-guided biopsy demonstrated high diagnostic accuracy and might constitute a valid substitute for random biopsies during endoscopic surveillance for dysplasia in BE.


Lactate dehydrogenase and malate dehydrogenase: Potential antiparasitic targets for drug development studies.
Parasitic diseases remain a major public health concern for humans, claiming millions of lives annually. Although different treatments are required for these diseases, drug usage is limited due to the development of resistance and toxicity, which necessitate alternative therapies. It has been shown in the literature that parasitic lactate dehydrogenases (LDH) and malate dehydrogenases (MDH) have unique pharmacological selective and specificity properties compared to other isoforms, thus highlighting them as viable therapeutic targets involved in aerobic and anaerobic glycolytic pathways. LDH and MDH are important therapeutic targets for invasive parasites because they play a critical role in the progression and development of parasitic diseases. Any strategy to impede these enzymes would be fatal to the parasites, paving the way to develop and discover novel antiparasitic agents. This review aims to highlight the importance of parasitic LDH and MDH as therapeutic drug targets in selected obligate apicoplast parasites. To the best of our knowledge, this review presents the first comprehensive review of LDH and MDH as potential antiparasitic targets for drug development studies.


Gas chromatographic-mass spectrometric analysis of diols and tetrols from reactions of polycyclic aromatic hydrocarbon epoxides with hemoglobin.
We have evaluated both electron ionization (EI) and negative-ion chemical ionization (NICI) methods for the analysis of trimethylsilyl derivatives of a series of polycyclic aromatic hydrocarbon (PAH) alcohols including styrene diol, benzo[e]pyrene diol and tetrols, cyclopenta[c,d]pyrene diols, benzo[a]pyrene-4,5-diols, chrysene tetrols, benz[a]anthracene tetrols I and II, and syn- and anti-benzo[a]pyrene tetrols. NICI is the more sensitive method for all compounds except styrene diol. Detection limits are compound-dependent and range from 1 fmol for cyclopenta[c,d]pyrene diol to 1 pmol for benzo[e]pyrene diol. The EI detection limit for styrene diol is 60 fmol. PAH alcohols related to the compounds listed above were observed following hydrolysis of hemoglobin which had been reacted with PAH epoxides in vitro. Benzo[a]pyrene tetrols and a chrysene tetrol were observed following hydrolysis of hemoglobin isolated from human smokers' blood. Hydrolysis of styrene oxide treated hemoglobin in 18O-labeled water revealed at least two mechanisms of ester hydrolysis, including the BAL 1 pathway.


Ethical and Legal Concerns Associated With Withdrawing Mechanical Circulatory Support: A U.S. Perspective.
Hundreds of thousands of Americans have advanced heart failure and experience severe symptoms (e. g., dyspnea) with minimal exertion or at rest despite optimal management. Although heart transplant is an effective treatment for advanced heart failure, the demand for organs far exceeds the supply. Another option for these patients is mechanical circulatory support (MCS) provided by devices such as the ventricular assist device and total artificial heart. MCS alleviates symptoms, prolongs life, and provides a "bridge to transplant" or a decision regarding future management such as "destination therapy," in which the patient receives lifelong MCS. However, a patient receiving MCS, or his/her surrogate decision-maker, may conclude ongoing MCS is burdensome and no longer consistent with the patient's healthcare-related values, goals, and preferences and, as a result, request withdrawal of MCS. Likewise, the patient's clinician and care team may conclude ongoing MCS is medically ineffective and recommend its withdrawal. These scenarios raise ethical and legal concerns. In the U.S., it is ethically and legally permissible to carry out an informed patient's or surrogate's request to withdraw any treatment including life-sustaining treatment (LST) if the intent is to remove a treatment perceived by the patient as burdensome and not to terminate intentionally the patient's life. Under these circumstances, death that follows withdrawal of the LST is due to the underlying disease and not a form of physician-assisted suicide or euthanasia. In this article, frequently encountered ethical and legal concerns regarding requests to withdraw MCS are reviewed: the ethical and legal permissibility of withholding or withdrawing LSTs from patients who no longer want such treatments; what to do if the clinician concludes ongoing LST will not result in achieving clinical goals (i.e., medically ineffective); responding to requests to withdraw LST; the features of patients who undergo withdrawal of MCS; the rationale for advance care planning in patients being considered for, or receiving, MCS; and other related topics. Notably, this article reflects a U.S. perspective.


Asthma guidelines: comparison of the National Heart, Lung, and Blood Institute Expert Panel Report 4 with Global Initiative for Asthma 2021.
Asthma continues to be a prevalent respiratory disease that affects lives within the United States and worldwide. Clinical asthma guidelines based on scientific evidence on testing and therapeutic interventions are needed to control this disease better. To meet this need, the NAEPP (National Asthma Education and Prevention Program) and GINA (Global Initiative for Asthma) were formed to assist with best practice diagnosis and treatments for asthma. This paper reviews the subtle differences and similarities between the most recent recommendations put forth by NAEPP 2020 and GINA 2021, mainly examining the six selected topics, as well as methodology, guidance on emerging topics, and implementation. In December 2020, the National Asthma Education and Prevention Program Coordinating Committee released their focused update on fraction of exhaled nitric oxide, indoor allergen mitigation, inhaled corticosteroids, long-acting muscarinic antagonists, allergen immunotherapy, and bronchial thermoplasty. The Global Initiative for Asthma comprehensive document is published annually as a framework for all nations. Therefore, it is timely to consider the National Asthma Education and Prevention Program Coordinating Committee 2020 in relation to the GINA 2021. The comparison provides a better understanding of evidence-based recommendations for asthma. The NAEPP 2020 and GINA 2021 will equip providers with the knowledge to provide their patients with the best and most updated asthma care.


Chronic modulation of serotonergic neurotransmission with sertraline attenuates the loudness dependence of the auditory evoked potential in healthy participants.
The loudness dependence of the auditory evoked potential (LDAEP) has been reported to be an effective non-invasive measure of central serotonergic neurotransmission. However, acute manipulations of the serotonergic system in humans and animals have yielded inconsistent findings. In this study, we examined the chronic effect of serotonergic manipulation using the selective serotonin reuptake inhibitor, sertraline, on the LDAEP. In addition, we examined the influence of 5-HTTLPR genotype and individual differences in plasma drug concentrations on the LDAEP. The study utilised a double-blind, placebo-controlled, between-group design in which 40 (24 female) healthy adults (M age = 22.0 years, SE = 0.7) were tested following placebo or sertraline for an average of 24 days. The LDAEP was assessed 6 h post-final dose, and changes in the slope of amplitude of the N1/P2 across intensities (60, 70, 80, 90, 100 dB) were examined at Cz. The sertraline group had a significantly smaller LDAEP than the placebo group [F(1,38) = 5.97, p = 0.02]. Drug plasma levels did not correlate with the LDAEP in the sertraline group, and there was no influence of 5-HTTLPR genotype. We show for the first time that chronically modulating serotonin neurotransmission alters the LDAEP in healthy adults, consistent with extant literature indicating a moderating role of serotonin on this neurophysiological biomarker. The findings from this study together with previous studies suggest that the LDAEP may be a more sensitive marker of long-term or chronic rather than acute changes in the serotonin system.


Bone Morphogenic Protein Signaling and Melanoma.
Malignant melanoma is a deadly form of skin cancer caused by neoplastic transformation of melanocytic cells. Despite recent progress in melanoma therapy, by inhibition of activated oncogenes or immunotherapy, survival rate for metastatic melanoma patients remains low. The remarkable phenotypic plasticity of melanoma cells allows for rapid development of invasive properties and metastatic tumors, the main cause of mortality in melanoma patients. Phenotypic and molecular analyses of developing tumors revealed that epithelial-mesenchymal transition (EMT), a cellular and molecular mechanism, controls transition from mature melanocyte to less differentiated melanocyte lineage progenitor cells forming melanoma tumors. This transition is facilitated by persistence of transcriptional regulatory circuit characteristic of embryonic stage in mature melanocytes. Switching of the developmental program of mature melanocyte to EMT is induced by accumulated mutations, especially targeting BRAF, N-RAS, or MEK1/2 signaling pathways, and further promoted by dynamic stimuli from local environment including hypoxia, interactions with extracellular matrix and growth factors or cytokines. Recent reports demonstrate that signaling mediated by transforming growth factor-β (TGF-β) and bone morphogenic proteins (BMPs) play critical roles in inducing EMT by controlling expression of critical transcription factors. BMPs are essential modulators of differentiation, proliferation, apoptosis, invasiveness, and metastases in developing melanoma tumors. They control transcription and epigenetic landscape of melanoma cells. Better understanding of the role of BMPs may lead to new strategies to control EMT processes in melanocyte cell lineage and to achieve clinical benefits for the patients.


Human Health Risk Assessments of Trace Metals on the Clam Corbicula javanica in a Tropical River in Peninsular Malaysia.
This study aimed to analyse ten trace metal concentrations in the edible part of the freshwater clam Corbicula javanica and to provide a critical assessment of the potential risks to human health through consumption of this clam as food based on well-established indices and food safety guidelines. The clams were captured from a pristine original site and transplanted to other sites with different environmental qualities. The trace metal levels in the edible total soft tissue (TST) of the clam were below those of the food safety guidelines referred to except for Pb, which exceeded the permissible limit set by the European Commission (2006) and the US Food and Drug Administration/ Center for Food Safety and Applied Nutrition); Interstate Shellfish Sanitation Conference. (USFDA/CFSAN; ISSC) (2007). The estimated daily intake (EDI) values of the clam were found to be lower than the oral reference dose and the calculated target hazard quotient (THQ) and total THQ were found to be less than 1. Therefore, in conclusion, the human health risk for consumption of TST of C. javanica at both average and high-level were insignificant regardless of the environment it was exposed to.


Characterizing dynamic relationships between burning rate and pollutant emission rates in a forced-draft gasifier stove consuming biomass pellet fuels.
Biomass is a dominant solid fuel type worldwide. Traditional biomass combustion leads to severe indoor and ambient environmental problems. Biomass pellet utilization in forced-draft gasifier stoves is regarded as an improved approach to these problems. Previous studies on forced-draft biomass stoves mainly considered average emission amounts and lacked details of the combustion properties and dynamic correlations between emissions and combustion. This study used a dynamic measurement system to test a typical forced-draft gasifier stove consuming wood pellets and maize straw pellets. Real-time fuel burning rate, that partly reflects the combustion performance, and CO, NOx and PM2.5 emission rates, over a whole combustion course, were monitored. In all tests, the burning rate rose to a high and stable level, and then sharply subsided. CO, NOx and PM2.5 emission rates varied across the combustion course. CO (NOx) emissions have a negative (positive) logarithmic linear relationship with burning rate, while no consistent relationship was observed for PM2.5 emission rate. The identified relationships between burning rate and pollutant emission rates suggest the possibility of estimating emission performance of forced-draft biomass pellet stoves based on combustion indicators, or vice versa.


Factors associated with fainting: before, during and after whole blood donation.
BACKGROUND Whole blood (WB) donation encompasses several periods during which some donors faint. Identification of factors associated with fainting during each period should guide intervention strategies. Reducing faint reactions may reduce donor injuries and disability. METHODS Blood donation was divided into three periods: Period 1 - registration; Period 2 - phlebotomy; and Period 3 - post-phlebotomy. Period 3 consists of two sub-periods (3A - on-site and 3B - off-site). For each Period, stratified rates of fainting in relation to various donor and donation characteristics were calculated and multivariable logistic regression analyses to identify factors associated with fainting were conducted. Donor injuries in each period were also analysed. RESULTS Of the 956 766 donors registered in 2007, 554 534 (58%) donated WB. There were 43 fainting episodes and two injuries in Period 1 and 1520 faints and 73 injuries in Periods 2 and 3. Regression analyses showed that youth and donor first-time status are associated with fainting in all periods; but most significantly in Period 1. Small estimated blood volume is notably not a factor in Period 1 but is significant in Periods 2 and 3. The highest injury rate is seen in Period 3A (0·07 and 0·09/1000 donations) for male and female donors, respectively. CONCLUSIONS Variability in factors associated with fainting across defined periods of the donation process suggest differing underlying mechanisms and the possibility that interventions for the reactions most associated with injury during each time period can be designed. The highest rate of injury per donation occurred in ambulating donors.


Retrocyclins and their activity against HIV-1.
Primate theta-defensins are physically distinguished as the only known fully-cyclic peptides of animal origin. Humans do not produce theta-defensin peptides due to a premature stop codon present in the signal sequence of all six theta-defensin pseudogenes. Instead, since the putative coding regions of human theta-defensin pseudogenes have remained remarkably intact, their corresponding peptides, called "retrocyclins", have been recreated using solid-phase synthetic approaches. Retrocyclins exhibit an exceptional therapeutic index both as inhibitors of HIV-1 entry and as bactericidal agents, which makes retrocyclins promising candidates for further development as topical microbicides to prevent sexually transmitted diseases. This review presents the evolution, antiretroviral mechanism of action, and potential clinical applications of retrocyclins to prevent sexual transmission of HIV-1.


"Needle" hidden in silk floss: Inactivation effect and mechanism of melamine sponge loaded bismuth oxide composite copper-metal organic framework (MS/Bi2O3@Cu-MOF) as floating photocatalyst on Microcystis aeruginosa.
Photocatalytic technology showed significant potential for addressing the issue of cyanobacterial blooms resulting from eutrophication in bodies of water. However, the traditional powder materials were easy to agglomerate and settle, which led to the decrease of photocatalytic activity. The emergence of floating photocatalyst was important for the practical application of controlling harmful algal blooms. This study was based on the efficient powder photocatalyst bismuth oxide composite copper-metal organic framework (Bi2O3 @Cu-MOF), which was successfully loaded onto melamine sponge (MS) by sodium alginate immobilization to prepare a floating photocatalyst MS/Bi2O3 @Cu-MOF for the inactivation of Microcystis aeruginosa (M. aeruginosa) under visible light. When the capacity was 0.4 g (CA0.4), MS/Bi2O3 @Cu-MOF showed good photocatalytic activity, and the inactivation rate of M. aeruginosa reached 74.462% after 120 h. MS/Bi2O3 @Cu-MOF-CA0.4 showed a large specific surface area of 30.490 m2/g and an average pore size of 22.862 nm, belonging to mesoporous materials. After 120 h of treatment, the content of soluble protein in the MS/Bi2O3 @Cu-MOF-CA0.4 treatment group decreased to 0.365 mg/L, the content of chlorophyll a (chla) was 0.023 mg/L, the content of malondialdehyde (MDA) increased to 3.168 nmol/mgprot, and the contents of various antioxidant enzymes experienced drastic changes, first increasing and then decreasing. The photocatalytic process generated·OH and·O2-, which played key role in inactivating the algae cells. Additionally, the release of Cu2+ and adsorption of the material also contributed to the process.


COVID-19 and the city: Did urbanized countries suffer more fatalities?
In this paper we derive a theoretical model of the spread of a viral infection which we use as basis for an estimation strategy to test four interrelated hypotheses on the relationship between country-level COVID-19 mortality rates and the extent of urban development. Using data covering 81 countries we find evidence that countries with a higher population density, a higher share of the urban population living in the largest city, and countries with a higher urbanization rate had on average the same or fewer COVID-19 fatalities compared to less urbanized countries in 2020. Even though COVID-19 spreads faster in cities, fatalities may be lower, conditional on economic development, trust in government, and a well-functioning health care system. Generally, urbanization and city development are associated with economic development: with the resources urbanized countries have, it is easier for them to manage and maintain stricter lockdowns, and to roll out effective pharmaceutical interventions.


Distinct proteinase 3-induced cytokine patterns in Wegener´s granulomatosis, Churg-Strauss syndrome, and healthy controls.
To analyse whether a specific cytokine pattern is elicited in response to the autoantigen proteinase 3 (PR3) in active Wegener's granulomatosis (WG). Six-colour flow cytometry was used to analyse cytokine production and surface markers of the total CD4+ T-cell population ex vivo and in PR3-stimulated T-cell lines of patients with active PR3-ANCA-positive WG, PR3-ANCA-negative Churg-Strauss syndrome (CSS), and healthy controls (HC). The cytokine response of the total PB CD4+ T cell population was skewed towards distinct pro-inflammatory cytokine patterns in WG (Th1-type) and CSS (Th17, Th1-/Th2-type). Th2-type as well as Th17 cell populations including Th17/Th1, Th17/Th2 and Th22 cells were elicited in response to PR3 stimulation in WG. In contrast, CSS patients displayed a Th2-type dominated response following PR3 stimulation. These data suggest that the cytokine response of the total CD4+ T-cell population and PR3-specific cells is influenced by the underlying disorder.


In silico interactions of statins with cell death-inducing DNA fragmentation factor-like effector A (CIDEA).
Statins are the low-density lipoproteins (LDL)-cholesterol-lowering drugs of first choice and are used to prevent the increased risk of cardiovascular and cerebrovascular diseases. Although some of their effects are well known, little is known about their ability to regulate other lipid-related proteins which control apoptotic mechanisms. The aim of this study was to explore whether statins can bind to cell death-inducing DNA fragmentation factor-like effector A (CIDEA), which might be a possible pleiotropic mechanism of action of these drugs on the modulation of apoptosis and lipid metabolism. The structures of statins were subjected to molecular docking and dynamics with the human CIDEA protein to investigate the interaction pattern and identify which residues are important. The docking results indicated that atorvastatin and rosuvastatin showed the best interaction energy (-8.51 and -8.04 kcal/mol, respectively) followed by fluvastatin (-7.39), pitavastatin (-6.5), lovastatin (-6.23), pravastatin (-6.04) and simvastatin (-5.29). Atorvastatin and rosuvastatin were further subjected to molecular dynamics at 50 ns with CIDEA and the results suggested that rosuvastatin-CIDEA complex had lower root-mean square deviation and root-mean square fluctuation when compared with atorvastatin-CIDEA. Since two arginine residues -ARG19 and ARG22-were identified to be common for the interaction with CIDEA, a single-point mutation was induced in these residues to determine whether they are important for binding interaction. Mutation of these two residues seemed to affect mostly the interaction of atorvastatin with CIDEA, suggesting that they are important for the binding and therefore indicate another possible metabolic mechanism of the pleiotropic effects of this statin.


pH-dependent transport of procainamide in cultured renal epithelial monolayers of OK cells: consistent with nonionic diffusion.
1. Previous studies suggest that procainamide is a substrate for organic cation/proton antiport. In order to study the coupling between procainamide flux and proton flux in greater detail we investigated the effects of extracellular procainamide addition upon intracellular pH in cultured monolayers of renal OK cells. Intracellular pH was monitored by use of BCECF as a probe. 2. Apical addition of procainamide (10 mM) caused a significant alkalinisation of intracellular pH. Basolateral addition of procainamide was equally effective in raising intracellular pH. A similar alkalinisation was found in two other renal cell lines: MDCK strain 1 and LLCPK1. 3. In contrast, both tetraethylammonium and N-methylnicotinamide, archetypal substrates for organic cation/proton antiport were without effect upon intracellular pH. 4. At physiological pH values, procainamide exists as a neutral weak base (B) and its conjugate weak acid (BH+). To test which species of procainamide was responsible for the alkalinisation, experiments in which [B] was kept constant whilst [BH+] was varied from 1.15 mM to 7.25 mM were performed. The results suggested that the neutral weak base (B) was the permeant species. 5. Procainamide efflux from procainamide-loaded cell monolayers resulted in a significant acidification of intracellular pH. As with procainamide uptake, this result could be ascribed to the movement of neutral weak base. 6. These effects of procainamide upon intracellular pH are consistent with nonionic diffusion of procainamide rather than an interaction of procainamide with the organic cation/proton antiporter. In addition, the results suggest that organic cation/proton antiport is not highly expressed in OK cells.


Omega filter installed in the 1MV microscope of Kyushu University.
A 1.25MV high-voltage electron microscope with a B-type omega filter has been successfully installed at Kyushu University. An image detection chamber has been set inside a concrete block below the ground level without changing the frame structure for anti-vibration. Nearly the same design as that for the 200kV microscope has been kept for the present omega filter except for its size. A new pre- and post-filter lens system with rotation-free imaging has been designed. Energy resolution, beam shape and stability of the filter have been measured. Some application data have been obtained to demonstrate the performance of the filter.


Prognostic Significance of Heart Rate and Beta-Blocker Use in Sinus Rhythm in Patients with Heart Failure and Preserved Ejection Fraction.
Prognostic significance of heart rate (HR) in heart failure with preserved ejection fraction (HFpEF) remains poorly understood. To evaluate the association of HR and beta-blocker use with all-cause mortality and the optimal HR range in patients with HFpEF and sinus rhythm (SR). During a follow-up of 2.7 years (IQR 1.2-4.1 years), the 330 patients with median age 73 (IQR 64-79) years, 52.1% men, were included. HFpEF was defined as patients with EF ≥ 50%. The outcome measure was all-cause mortality. In total, 96 (29.1%) of patients with HFpEF and SR died. A linear tendency between HR and mortality was observed in SR. Compared to the reference strata HR ≤ 60 bpm, HR increment was associated with progressively increased risk in mortality (Chi-square = 13.90, Log rank P = 0.001) by Kaplan-Meier analyses. Univariate Cox regression showed that in SR, compared with that in HR 61-80 bpm, the unadjusted hazard ratios for mortality were 0.41 (95% CI 0.23-0.74, P = 0.003) in HR ≤ 60 bpm, 1.38 (95% CI 0.85-2.24, P = 0.189) in HR > 80 bpm. Multivariate Cox regression showed that compared with that in HR 61-80 bpm, the adjusted hazard ratios for mortality were 0.37 (95% CI 0.19-0.75, P = 0.005) in HR ≤ 60 bpm, 0.96 (95% CI 0.52-1.74, P = 0.899) in HR > 80 bpm. Univariate Cox regression showed that the unadjusted hazard ratios for mortality were 0.52 (95% CI 0.33-0.84, P = 0.003) in patients with beta-blocker as compared patients without beta-blocker. Multivariate Cox regression showed that the adjusted hazard ratios for mortality were 0.48 (95% CI 0.26-0.87, P = 0.016) in patients with beta-blocker as compared patients without beta-blocker. HR is independently associated with increased all-cause mortality in SR and a lower HR (≤ 60 bpm) is favorable for better outcome in HFpEF patients with SR. Beta-blocker use is associated with reduced mortality and a lower HR is associated with reduced mortality in HFpEF patients with SR.


Development and characterization of multiplex panels of polymorphic microsatellite loci in giant liver fluke Fascioloides magna (Trematoda: Fasciolidae), using next-generation sequencing approach.
The microsatellite markers were designed for the giant liver fluke, Fascioloides magna, veterinary important liver parasite of free-living and domestic ruminants. Due to its geographic distribution (five enzootic regions across USA and Canada, three permanent European foci) and invasive character, F. magna is an interesting model for population genetics. Out of 667 amplicon candidates generated after NGS, 118 provided the best resolution and were tested with PCR analysis. In total, 56 yielded PCR products of expected size and in 36 of them the declared repetitive motif was identified by Sanger sequencing. After fragment analysis, 12 loci were proved to be polymorphic in individuals from one tested European and four North American populations. These loci were selected for setup of multiplex STR assays and utilized in genotyping of larger sample cohort. The outputs of statistical analyses indicate further global application of 11 conclusive loci in population genetics of the parasite.


A bridge from HeartMate XVE to HeartMate 3.
Cardiac recovery after left ventricular assist device (LVAD) implantation is rare. Recurrent heart failure after device explantation is also rare. We describe a patient who is the recipient of a third-generation LVAD due to recurrent heart failure nearly one decade after successfully being bridged to recovery after implantation of a first-generation LVAD.


Mitochondrial DNA from hepatocytes induces upregulation of interleukin-33 expression of macrophages in nonalcoholic steatohepatitis.
In the present study, we propose that lipotoxicity induces the release of mitochondrial DNA (mtDNA) from hepatocytes, which in turn upregulates IL-33 expression in macrophages. The mtDNA levels of plasma were determined in methionine- and mholine-deficient diet (MCD)-fed mice and NASH patients. Cultured hepatocytes were pre-incubated with Mito-TEMPO or rapamycin and were then stimulated with palmitic acid. The mtDNA levels in the cytosol were measured. The mtDNA from hepatocytes of mice was added to bone marrow-derived macrophages (BMDMs) in the presence of IRS (TLR9 antagonist). The expression of IL-33 in BMDMs was measured. Levels of mtDNA were higher in NASH patients and MCD-fed mice. Treatment of hepatocytes with palmitic acid in vitro induced mtDNA release into cytosol, which was attenuated by mito-TEMPO or rapamycin, and aggravated by inhibition of autophagy. Treatment of BMDMs with mtDNA enhanced IL-33 expression, which was attenuated by knockdown of TLR9. Treatment of BMDMs with mtDNA enhanced lipopolysaccharide (LPS)-induced production of IL-1β and TNF-α, which was attenuated by pretreatment with soluble ST2. mtDNA released from injured hepatocytes under lipid overload induced the upregulation of IL-33 expression in macrophages via TLR9, and enhanced LPS-induced inflammatory cytokine production.


Autogenous dermis-fat orbital impant for anophthalmic socket.
To our knowledge, there is no report of dermis-fat graft (DFG) implant for orbital reconstruction from Oman. We hereby presented a case report of a 10-year-old boy with a blind and painful left eye secondary to penetrating eye injury presented with implant extrusion following evisceration with a polymethyl methacrylate implant. The evisceration procedure was converted to enucleation and a DFG orbital implant was then performed. Postoperatively, the graft was observed to be well integrated with the host orbital tissues and had good cosmetic and functional outcomes.


Extracranial carotid artery aneurysms following accidental injury: ten years experience.
Extracranial carotid artery aneurysms secondary to accidental injury are rare. We have seen eight lesions of this type in the last 10 years. The aneurysm was produced by blunt trauma in four patients, penetrating shrapnel injury in two, stabbing and electrical injury in one each. The left side was involved in seven patients. The internal and common carotid artery were each involved in four patients and the lesion was unilocular in five. These lesions often produce non-specific symptoms and may mimic neoplastic or inflammatory masses: a mistaken diagnosis of tonsillar abscess in one patient resulted in incision and drainage before an intravenous digital subtraction angiogram (IV-DSA) correctly identified the abnormality. IV-DSA is ideal for pre-operative assessment of these patients. Awareness of these lesions is essential since definitive surgical repair is possible. All patients in the present study underwent successful surgical repair.


Multifunctional Water Drop Energy Harvesting and Human Motion Sensor Based on Flexible Dual-Mode Nanogenerator Incorporated with Polymer Nanotubes.
In the world of increasing energy consumption, nanogenerators have shown great potential for energy harvesting and self-powered portable electronics. Herein, a flexible and dual-mode triboelectric nanogenerator (TENG) combining both vertical contact-separation and single electrical modes has been developed to convert environmental mechanical energy into electricity using highly encapsulated and multifunctional strategies. By introducing the polymer melt wetting technique, polymer nanotubes are fabricated on the surface of the TENG, which provides self-cleaning and hydrophobic features beneficial for water drop energy harvesting using the device. In such mechanical energy harvesting, the maximum output power of 0.025 mW and the open-circuit voltage of 41 V can be achieved. By designing the dimensions of the device, the dual-mode TENG is utilized as a self-powered sensor to detect human body motions such as phalanges' movement of fingers. The fabricated dual-mode TENG promotes the development of energy-harvesting and self-powered human motion sensors for artificial intelligent prosthetics, human kinematics, and human body recovery treatment.


Redox properties and active center of phototrophic bacteria hydrogenases.
It is shown that the activity of phototrophic bacteria hydrogenases depends on the redox potential (Eh) of the medium. Hydrogenase from the purple sulfur bacterium Thiocapsa roseopersicina strain BBS reversibly activates H2 at Eh less than -290 mV (pH 7.0). When Eh is increased from -290 to -170 mV, the enzyme is converted into an inactive form which is accompanied by one-electron oxidation of its Fe-S cluster. In contrast, the hydrogenases of the purple nonsulfur bacterium Rhodobacter capsulatus B10 and the green sulfur bacterium Chlorobium limicola forma thiosulfatophilum exhibit maximum activity at Eh greater than -300 mV, favourable only for H2 uptake. When Eh decreases the activities of these enzymes drop dramatically; this accounts for their unidirectional effect directed mainly towards H2 uptake. Such dependence on Eh of activity of hydrogenases from these bacteria correlates with their physiological function in the metabolism of phototrophic bacteria, i.e. with the catalysis of the H2 uptake reaction. Hydrogenases from purple bacteria contain nickel and a single Fe-S cluster. Metal chelators do not affect the activity of these enzymes, which indicates that iron and nickel are tightly bound to the apoprotein. Sulfhydryl compounds irreversibly inactivate T. roseopersicina hydrogenase by 30-40% in the presence of sulfide. Acetylene and carbon monoxide are reversible inhibitors of the enzyme. EPR and inhibitory analysis indicate a direct interaction of H2 with the nickel ion in the active center of the T. roseopersicina hydrogenase.


Identification of Sp1-binding sites in the CD11c (p150,95 alpha) and CD11a (LFA-1 alpha) integrin subunit promoters and their involvement in the tissue-specific expression of CD11c.
The leukocyte integrins LFA-1 (CD11a/CD18) and p150,95 (CD11c/CD18) mediate cell-cell and cell-extracellular matrix interactions during inflammatory responses and signal transduction into the cytoplasm. While the CD11a integrin subunit is expressed on all leukocytes, CD11c is almost exclusively expressed on cells of the myeloid lineage and on activated B lymphocytes. Its expression is regulated during cell activation and differentiation by transcriptional mechanisms. We have previously demonstrated that the proximal region of the CD11c promoter directs tissue-restricted and developmentally-regulated expression of reporter genes. Structural studies by electrophoretic mobility shift assays have demonstrated the presence of two Sp1-binding sites at -70 (Sp1-70) and -120 (Sp1-120) which mediate the Sp1 transactivation of the CD11c promoter in Sp1-defective SL2 cells, and which are involved in cell lineage-specific DNA-protein interactions, as demonstrated by footprinting in vivo. More importantly, mutation of either Sp1 site inhibited the activity of the CD11c promoter both in myeloid U937 cells and the CD11c-expressing B lymphoblastoid JY cell line, while the opposite effect was observed in the CD11c-negative epithelial HeLa cell line, demonstrating the involvement of both Sp1-binding sites in the basal and the tissue-restricted expression of the CD11c integrin subunit gene. Interestingly, the analysis of the CD11a proximal promoter also revealed the existence of an Sp1-binding site at -70, indicating a common role for these cis-acting elements in the transcription of the leukocyte integrin alpha subunit genes. The binding of Sp1 to the regulatory regions of the leukocyte integrin genes raises the possibility that the retinoblastoma susceptibility gene product is implicated in integrin expression through its functional interaction with Sp1, thus establishing a link between integrin-dependent leukocyte adhesiveness and the state of cellular differentiation/proliferation.


A Meta-Analysis of the Impact of Obesity, Metabolic Syndrome, Insulin Resistance, and Microbiome on the Diagnosis of Barrett's Esophagus.
The etiology and pathogenesis of Barrett's esophagus (BE) have been widely studied during recent decades. However, the association between BE and possible risk factors, including abdominal obesity (AO), metabolic syndrome (MetS), insulin resistance (IR), and the microbiome has not reached a consensus and lacks a systematic assessment. The purpose of our study is to evaluate, quantify, and summarize the association between these factors and BE risk. A systematic search of Pubmed, Embase, and Cochrane Library databases was performed to identify relevant studies before September 2018. Studies were estimated with the OR, the weighted mean difference (WMD), and the 95% CI by using a random effects model. Subgroup analysis and publication bias were also performed. A total of 46 citations were included in the analysis, and 119,273 subjects were analyzed (AO 13, MetS 15, IR 9, and microbiome: 9). The pooled results showed that AO (p < 0.01, OR 1.30, 95% CI 1.11-1.52, I2 = 31.9%), MetS (p < 0.01, OR 1.68, 95% CI 1.40-2.01, I2 = 87.6%), and IR (p < 0.01, WMD 0.23, 95% CI 0.11-0.35, I2 = 55.8%) were all significantly associated with an increased risk of BE, but except for the microbiome (p > 0.05, OR 1.27, 95% CI 0.66-2.43, I2 = 46.7%). In addition, subgroup analyses were stratified by waist-to-hip ratio, waist circumference, body mass index, diagnosis criteria, strain type, geographical region, and study design, respectively. Moreover, we observed no evidence of publication bias in Egger's and Begg's tests. Our study reveals that AO, MetS, and IR are significantly associated with BE risk, except for the microbiome. The mechanism of BE induced by 3 risk factors should be further explored.


Role of plasmid-coded RNA and ribonuclease III in plasmid DNA replication.
An in vitro replication system has been used to study the control of DNA replication of the relaxed plasmids Col E1 and RSF1030. An RNA transcript approximately 100 nucleotides long is synthesized during the in vitro DNA replication reaction. This RNA is synthesized approximately 450 bp away from the origin of replication. A small insertion in the coding sequence for the RNA made from Col E1 DNA leads to a larger RNA species and simultaneously to an increase in plasmid copy number. Revertants missing the specific insertion show shorter RNA transcripts and wild-type copy number. Although plasmids Col E1 and RSF1030 have no extensive sequence homology, the RNA synthesized during RSF1030 replication has almost the same mobility as the Col E1 RNA on polyacrylamide gels and hybridizes to the Col E1 origin region. Extracts prepared from mutants of Escherichia coli deficient in ribonuclease III do not replicate RSF1030 or Col E1 plasmids in vitro. When supplemented with homogeneous RNAase III, such extracts do support DNA replication on these templates, indicating that RNAase III is required for DNA replication. We propose that the 100 nucleotide RNA species is involved in regulating the initiation of DNA replication of these plasmids, and that RNAase III may be involved in processing this RNA.


Comparative study between effects of ginkgo biloba extract and extract loaded on gold nanoparticles on hepatotoxicity induced by potassium bromate.
In human organs, potassium bromate (KBrO3) produces toxicity. The main causes of KBrO3 hepatotoxicity are the formation of reactive oxygen species (ROS) and DNA damage. The purpose of this study is to show how ginkgo biloba extract (GBE) and extract loaded with nanogold particles (GBE@AuNPs) affect hepatotoxicity caused by KBrO3. The rats were separated into eight groups: control (group I), GBE (group II), AuNPs (group III), GBE@AuNPs (group IV), KBrO3 (group V), KBrO3 and GBE (group VI), KBrO3 and AuNPS (group VII), and KBrO3 and GBE@AuNPs (group VIII). KBrO3 generated DNA damage spots in a comet assay, which were associated with increased inflammatory indicators (IL-6), decreased anti-apoptotic Bcl-2, and increased apoptotic markers (Bax and caspase-3). The inflammatory, apoptotic, and ultrastructural alterations in liver tissue produced by KBrO3 were reduced in treated groups VI, VII, or VIII. The hepatotoxic effects of KBrO3 were reduced when GBE, AuNPs, or GBE@AuNPs were used; the particular GBE@AuNPs were the most effective.


Chronic pelvic pain syndromes--traditional and novel therapies: part I surgical therapy.
To describe the role of various surgical therapies for the relief of pelvic pain. The latest studies involving surgical therapies for relief of pelvic pain are reviewed and the pros and cons are discussed. Laparoscopic removal of endometriotic implants should be performed if the surgical procedure is being performed for diagnostic purposes. Laparoscopic utersacral nerve ablation of endometriotic implants and presacral neurectomy may provide additional relief but require greater surgical skills and have significant risks, especially bleeding. There still is a role for complete hysterectomy usually with bilateral salpingo-oophorectomy. Recurrence rates following surgery relegate surgical procedures behind medical therapy, i.e., to be used only if medical therapy is failing. Not all pelvic pain is related to endometriosis. Some novel concepts as to common mechanisms involved in a large percentage of these pelvic pain syndromes leading to some novel highly effective medical therapies will be discussed in part II.


Breath biopsy, a novel technology to identify head and neck squamous cell carcinoma: A systematic review.
Head and neck cancers are a heterogeneous group of neoplasms, which together comprise the sixth most common cancer globally. Breath biopsies are a non-invasive clinical investigation that detect volatile organic compounds (VOCs) in exhaled breath. This systematic review examines current applications of breath biopsy for the diagnosis of head and neck squamous cell carcinoma (HNSCC), including data on efficacy and utility, and speculates on the future uses of this non-invasive detection method. Medline, PubMed, Web of Science, Cochrane and Scopus, as well as the grey literature were searched using a search strategy developed to identify relevant studies on the role of breath biopsy in the diagnosis of HNSCC. All included studies were subject to a thorough methodological quality assessment. The initial search generated a total of 1443 articles, 20 of which were eligible for review. A total of 660 HNSCC samples were investigated across the included studies. 3,7-dimethylundecane and benzaldehyde were among several VOCs to be significantly correlated with the presence of HNSCC compared to healthy controls. We show that current breath biopsy methods have high accuracy, specificity and sensitivity for identifying HNSCC. However, further studies are needed given the reported poor quality of the included studies.


A type-2C protein phosphatase (GhDRP1) participates in cotton (Gossypium hirsutum) response to drought stress.
GhDRP1 acts as a negatively regulator to participate in response to drought stress possibly by modulating ABA signaling pathway and flavonoid biosynthesis pathway which affects stomata movement and thus water loss, ROS scavenging enzymes, and proline accumulation in cotton. Type-2C protein phosphatases (PP2C) may play important roles in plant stress signal transduction. Here, we show the evidence that a cotton PP2C protein GhDRP1 participates in plant response to drought stress. GhDRP1 gene encodes an active type-2C protein phosphatase (PP2C) and its expression is significantly induced in cotton by drought stress. Compared with wild type, the GhDRP1 overexpression (OE) transgenic cotton and Arabidopsis displayed reduced drought tolerance, whereas GhDRP1-silenced (RNAi) cotton showed enhanced drought tolerance. Under drought stress, malondialdehyde content was lower, whereas superoxide dismutase and peroxidase activities, proline content, stomata closure and relative water content were higher in GhDRP1 RNAi plants compared with those in wild type. In contrast, GhDRP1 OE plants showed the opposite phenotype under the same conditions. Expression levels of some stress-related and flavonoid biosynthesis-related genes were altered in GhDRP1 transgenic plants under drought stress. Additionally, GhDRP1 protein could interact with other proteins such as PYLs, SNF1-related protein kinase and GLK1-like protein. Collectively, these data suggest that GhDRP1 participates in plant response to drought stress possibly by modulating ABA signaling pathway and flavonoid biosynthesis pathway which affects stomata movement and thus water loss, ROS scavenging enzymes, and proline accumulation in cotton.


The Psychometric Properties of the Perceived Stress Scale When Used to Measure Stress Levels of Finnish Nursing Undergraduate Students.
Stress is an important issue in clinical nursing education because it may obstruct learning in clinical environments. This study aimed to translate, adapt, and investigate the psychometric properties of the Perceived Stress Scale (PSS), an instrument for measuring stress. Nursing students (N = 189) from five different universities of applied sciences participated in this study in 2018. The modified English version of the 29-item six-factor PSS was cross-culturally adapted into Finnish. Exploratory factor analysis was conducted to assess the scale's factor structure. Confirmatory factor analysis was performed to validate the "best fit" model. The proposed 16-item four-factor model showed excellent internal consistency, with a Cronbach's alpha value of 0.90. The results support the use of the 16-item four-factor stress scale to investigate stress among Finnish nursing students.


Confined to a tokenistic status: Social scientists in leadership roles in a national health research funding agency.
The idea of interdisciplinarity has been taken up by academic and governmental organisations around the world and enacted through science policies, funding programs and higher education institutions. In Canada, interdisciplinarity led to a major transformation in health research funding. In 2000, the federal government closed the Medical Research Council (MRC) and created the Canadian Institutes of Health Research (CIHR). From the outset, CIHR's vision and goals were innovative, as it sought to include the social sciences within its purview alongside more traditional health research sectors. The extent to which it has been successful in this endeavour, however, remains unknown. The aim of our study was to examine how CIHR's intentions to foster inclusiveness and cooperation across disciplines were implemented in the agency's own organisational structure. We focused on social scientists' representation on committees and among decision-makers between 2000 and 2015, one of the key mandates of CIHR being to include the social sciences within its remit and support research in this area. We examined the composition of the Governing Council, the Institute Scientific Directors, the Chairs of the College of Reviewers, and two International Review Panels invited by CIHR. We targeted these committees and decision-makers since they hold the power to influence the field of Canadian health research through the decisions they make. Our findings show that, while CIHR was created with the mandate to support the entire spectrum of health-related research-including the social sciences-this call for inclusiveness has not yet been materialized in the agency's organisational structure. Social scientists, as well as researchers from neighbouring disciplines such as social epidemiology, health promotion and the humanities, are still confined to low levels of representation within CIHR's highest echelons. This imbalance limits social scientists' input into health research in Canada and undermines CIHR's interdisciplinary ambition.


Distraction osteogenesis as followed by CT scan in Pierre Robin sequence.
The aim of this work was to assess the multislice CT scan for analysis of the craniofacial anatomic changes in Pierre Robin sequence both predistraction and postdistraction, and to assess the use of unidirectional internal distractors in this patient group. The study involved 11 patients. Their age at the time of distraction ranged from 2 to 7 months. Six were females and 5 were males. All had retromicrognathia, glossoptosis and obstructive sleep apnoea. All were diagnosed clinically and by CT scan. All were managed by distraction osteogenesis and were followed postoperatively by multislice CT. The distance between the base of the tongue and the posterior pharyngeal wall increased by a mean of 141%, and the total mandibular length increased by a mean of 26%. The increase in the distance between the hyoid bone and the posterior pharyngeal wall increased by a mean of 42% .The distance between the hyoid bone and the genoid process increased by a mean of 9%. Multislice CT scan was found to be a practical imaging technique to evaluate the morphologic changes in the airway and the mandible after distraction osteogenesis. It rules out the need for other traditional methods. Owing to the plasticity and malleability of the infant mandible that allow for sufficient bone remodelling, unidirectional internal distractors achieved a satisfactory maxillomandibular relationship which was tolerated by the infants and accepted by the parents.


Metabolic effects of medium chain triglyceride-enriched total parenteral nutrition in rats bearing Yoshida sarcoma.
The ability of medium chain triglyceride-enriched total parenteral nutrition to support host tissue in a model of cancer cachexia was assessed by measuring tumor growth, body weight, nitrogen balance, energy expenditure, leucine kinetics, fractional protein synthetic rate of tumor, liver, and abdominis rectus muscle, and plasma levels of glucose and albumin. Male Sprague-Dawley rats (85-90 gm) received 10(7) cells of viable Yoshida sarcoma subcutaneously on day 0. Control rats received injections of sterile saline. On day 10 rats underwent central venous cannulation and were randomized to one of three isocaloric diets. One group received amino acids and dextrose, while the other two groups were infused with amino acids, dextrose, and fat as either long chain triglyceride or a physical mixture of medium chain triglyceride: long chain triglyceride (3:1). On day 14 L-1-(14)C-leucine was added to the diet to study protein kinetics, and energy metabolism was measured by indirect calorimetry. Both tumor-bearing and nontumor-bearing rats demonstrated improved nitrogen balance when given medium chain triglyceride-enriched total parenteral nutrition. Tumor-bearing rats had reduced resting energy expenditure vs. nontumor-bearing, while rats receiving total parenteral nutrition without fat had significantly greater respiratory quotients. Tumor-bearing rats had lower total body weight vs. nontumor-bearing on day 10, but body weight of tumor-bearing and nontumor-bearing did not differ on day 14. Whole body protein breakdown decreased and leucine balance increased in tumor-bearing rats as compared to nontumor-bearing. Total liver mass was greater in tumor-bearing rats, but liver protein fractional protein synthetic rate decreased in tumor-bearing rats vs. nontumor-bearing. Tumor growth rate and fractional protein synthetic rate were not altered by the parenteral diet. The data confirm an altered metabolism in the tumor-bearing host, and suggest that medium chain triglyceride can better support host tissue.


Effects of asynchronous stimulation on the human quadriceps femoris muscle.
Examine the effects of asynchronously activating motor units of the human quadriceps femoris muscle during electrical stimulation. Two stimulation channels were used to activate the muscle. One pair of electrodes was placed over the vastus medialis (Channel 1) and another pair was placed over the vastus lateralis (Channel 2). All contractions were isometric. The stimulation frequency was 10 Hz for each channel and the effect of varying the delay between the two channels was tested. Synchronous activation of both channels produced the greatest forces and stimulating the muscle 180 degrees out of phase (ie, with a 50-msec delay) produced the least forces. Activating motor units asynchronously under certain conditions will be less efficient than synchronous activation. This study, therefore, helps to define the boundary conditions when asynchronous stimulation may be helpful.


Desynchrony induced by higher-order interactions in triplex metapopulations.
In a predator-prey metapopulation, two traits are adversely related: synchronization and persistence. A decrease in synchrony apparently leads to an increase in persistence and, therefore, necessitates the study of desynchrony in a metapopulation. In this article, we study predator-prey patches that communicate with one another while being interconnected through distinct dispersal structures in the layers of a three-layer multiplex network. We investigate the synchronization phenomenon among the patches of the outer layers by introducing higher-order interactions (specifically three-body interactions) in the middle layer. We observe a decrease in the synchronous behavior or, alternatively, an increase in desynchrony due to the inclusion of group interactions among the patches of the middle layer. The advancement of desynchrony becomes more prominent with increasing strength and numbers of three-way interactions in the middle layer. We analytically validate our numerical results by performing a stability analysis of the referred synchronous solution using the master stability function approach. Additionally, we verify our findings by taking into account two distinct predator-prey models and dispersal topologies, which ultimately supports that the findings are generalizable across various models and dispersal structures.


[Characterization and behaviour of lysosomal enzymes in tail tissue of xenopus larvae during involution].
1. The distribution of lysosomal enzymes obtained by density gradient centrifugation of cell-free extracts of Xenopus tail tissue was compared during growth and involution. The particles containing lysosomal enzymes were also characterized by means of electron microscopy. 2. Cytochromeoxidase is recovered to more than 90% in bound form (mitochondria), whereas lysosomal enzymes are characterized by a high proportion of soluble activity (up to 67%). The particle-bound activity ofβ-glucuronidase, cathepsin, and acid RNase show two peaks after centrifugation, in contrast to the activity of acid phosphatase, which is distributed over the whole gradient. During tail involution an increasing proportion of soluble activity is observed, especially for cathepsin and acid RNase. 3. Electronmicroscopical examination reveals a rather heterogeneous composition of the particle populations obtained by density gradient centrifugation. In fractions with highest activity of lysosomal enzymes various types of electron dense granules are found, thus precluding characterization of a specific lysosomal structure. 4. The distribution of enzymes after induction of tail involution with thyroxine was almost similar to the results obtained from spontaneously metamorphosing animals. Since actinomycin D inhibits the increase in lysosomal enzymes and tissue involution it is concluded that the synthesis of soluble acid hydrolases is a prerequisite of hormonal induced tissue involution.


Stabilization of multi-input hybrid fractional-order systems with state delay.
In this paper, the stabilization of a particular class of multi-input linear systems of fractional order differential inclusions with state delay using variable structure control is considered. First, the sliding surface with a fractional order integral formula is defined, and then the sufficient conditions for stability of the sliding surface are derived. Also, the concepts related to sliding control stabilization of differential inclusion systems with integer order are extended to differential inclusion systems with fractional order 0<q<1. Furthermore, for stabilization of fractional order systems with delay in the state space, a feedback and the concept of the norm of a state space is exploited. Finally, simulation results are provided to show the effectiveness of the proposed method.


Autonomy-supportive agents: whose support matters most, and how does it unfold in the workplace?
Managers and colleagues satisfy others' need for autonomy, but employees can also satisfy their own need by engaging in autonomy crafting practices. Although all three sources of autonomy support can benefit employee outcomes, they may not be equally beneficial. Furthermore, their benefits may not be straightforward, but rather a psychological process unfolding. To test these assumptions, the aim of the present study was twofold: to determine whether the different sources of support explained significantly different amounts of variance in autonomy satisfaction when compared and to understand the psychological process through which autonomy support from three sources influenced performance, more specifically, whether autonomy support indirectly affected performance through perceived autonomy satisfaction and work engagement in serial. In a sample of 278 employees, autonomy support from others (especially managers) and autonomy crafting played a role in autonomy satisfaction. Furthermore, the results indicated that autonomy support was associated with performance through its serial associations with autonomy satisfaction and work engagement. The results emphasized the importance of autonomy support for performance, enabling organizations to proactively design interventions to improve engagement and performance. The online version contains supplementary material available at 10.1007/s12144-022-03550-9.


Characterization of endopolygalacturonase (EC 184.108.40.206) from Aspergillus niger as glycoprotein by electrophoretic methods and lectin affino-blotting.
Chromatographically purified endopolygalacturonase (PG) from Aspergillus niger was deglycosylated with N-glycosidase F (PNGase F) and characterized by means of sodium dodecyl sulfate (SDS)-electrophoresis, polyacrylamide gel electrophoresis (PAGE) without denaturing agents, isoelectric focusing (IEF) and lectin affino-blotting. The results show that PG, which is apparently homogeneous in SDS-PAGE but heterogeneous in IEF and PAGE, consists of at least two polypeptide chains with different glycosylation patterns. The component with the higher electrophoretic mobility is deglycosylated with PNGase F and reacts with concanavalin A (Con A) and Galanthus nivalis agglutinin (GNA), indicating a "high mannose" or "hybrid"-type of glycoprotein (GP). The other component may contain O-glycosidically linked mannose, N-acetylglucosamine or glucose.


The Choice of Spinal Cord Stimulation Versus Targeted Drug Delivery in the Management of Chronic Pain: Validation of an Outcomes Predictive Formula.
In 2020, Mekhail et al published a formula that predicted the likelihood of a successful outcome for those who undergo spinal cord stimulation (SCS) for long-term pain management, based on retrospectively collected clinical and demographic data from one major medical center. The aim of this study is to validate such a predictive formula, prospectively, in a cohort of patients from multiple medical practices that are more representative of real-life clinical practice. For the study, 939 patients who underwent successful SCS or targeted drug delivery (TDD) trials at multiple independent medical centers in the USA were enrolled into the Medtronic product surveillance registry data base before they underwent SCS or TDD device implantation, from 2018 to 2020. The registry data were collected prospectively but not specifically for this study. The data examined included demographic information, pain diagnosis, pain scores (visual analog scale [VAS]), Oswestry Disability Index scores, and quality-of-life scores at baseline and six months after implant. Because our goal is to validate the previously published predictive formula, in addition to the outcomes data previously mentioned, we collected the variables necessary for such a task: sex, age, depression, the presence of neuropathic pain, spine-related pain diagnosis, and persistent spinal pain syndrome "post laminectomy syndrome." Spine-related pain diagnosis included subjects with chronic spine pain who never had back surgery and whose pain was not radicular nor neuropathic. Of 619 patients with SCS, 138 (22%) achieved ≥ 50% reductions of the baseline VAS at six months. The logistic model predicts SCS success with an area under the receiver operating characteristic curve (AUC) of 80% in the current validation data set. Of 320 patients with TDD, 147 (46%) achieved ≥ 50% reduction of the baseline VAS at six months. The logistic model predicts TDD success with an AUC of 78% in the current validation data set. The study provides real life validation of the previously published predictive formula(4).


Use of intramuscular prostaglandin for failure of mid-trimester abortion by another method.
Eight investigators, using a common protocol, studied the use of intramuscular (15S)-15-methyl prostaglandin F2 alpha to abort midtrimester pregnancies which had failed treatment by other methods in 398 cases. Results of treatment of 3 subgroups, defined by reason for primary treatment failure, are presented. The combined efficacy rate was 96.2% with 79.6% of the abortions being complete. The mean time from starting intramuscular therapy to successful abortion was 7.35 hours. The incidence of gastrointestinal side-effects was lower than that previously reported for systemically administered prostaglandins. Serious complications were not appreciably different from those reported for commonly used methods of second trimester abortion except for a slightly higher incidence of excessive bleeding requiring blood replacement. Advantages of this method over currently used methods of treating failures of primary attempts to induce midtrimester abortion by pharmacologic means are discussed.


Reactive desorption electrospray ionization mass spectrometry (DESI-MS) of natural products of a marine alga.
Presented here is the optimization and development of a desorption electrospray ionization mass spectrometry (DESI-MS) method for detecting natural products on tissue surfaces. Bromophycolides are algal diterpene-benzoate macrolide natural products that have been shown to inhibit growth of the marine fungal pathogen Lindra thalassiae. As such, they have been implicated in antimicrobial chemical defense. However, the defense mechanisms are not yet completely understood. Precise detection of these compounds on algal tissue surfaces under ambient conditions without any disruptive sample processing could shed more light onto the processes involved in chemical defense of marine organisms. Conventional DESI-MS directly on algal tissue showed relatively low sensitivity for bromophycolide detection. Sensitivity was greatly improved by the addition of various anions including Cl(-), Br(-), and CF(3)COO(-) into the DESI spray solvent. Chloride adduction gave the highest sensitivity for all assayed anions. Density functional optimization of the bromophycolide anionic complexes produced during DESI supported this observation by showing that the chloride complex has the most favorable binding energy. Optimized DESI protocols allowed the direct and unambiguous detection of bromophycolides, including A, B, and E, from the surface of untreated algal tissue.


Biosafety and biobanking: Current understanding and knowledge gaps.
Infectious disease outbreaks, such as 'Coronavirus disease 2019' (COVID-19), can constitute major global health threats with far-reaching consequences. As outbreaks develop, the international scientific community must provide high-quality scientific research-ready biological samples to solve the existing clinical and epidemiological questions to better combat the pandemic. Such examples are provided by dedicated biobank facilities, the latter collecting increasingly high volumes of biological samples. However, the more significant concentrations of infectious or potentially infectious biological materials can create a safety risk. The current short report describes the first attempt to identify the published scientific works on biobanking and safety. Three broad thematic areas have been identified: the physical security relevant to staff and sample integrity, the data safety aspects, and the governance parameters relating to the previous two. While the current publications reflect a broad alignment with existing standards and best practices in the biobanking field, they also demonstrate an opportunity for further in-depth work on this field in the post-COVID-19 era.


Evidences of autoregulation of hfq expression in Sinorhizobium meliloti strain 2011.
Riboregulation comprises gene expression regulatory mechanisms that rely upon the activity of small non-coding RNAs (sRNAs) and in most cases RNA binding proteins. In γ-proteobacteria, the Sm-like protein Hfq is a key player in riboregulatory processes, because it promotes sRNA-mRNA interactions and influences mRNA polyadenylation or translation. In the α-proteobacterium Sinorhizobium meliloti, the large number of detected small RNA transcripts and the pleiotropic effects of hfq mutations lead to the hypothesis that riboregulatory mechanisms are important in this soil microorganism to adjust gene expression both in free-living conditions and as a nitrogen-fixing endosymbiont within legume root nodules. In this study, homology modeling of S. meliloti Hfq protein and cross-complementation experiments of S. meliloti and Escherichia coli mutants indicates that hfq ( Sm ) encodes an RNA chaperone that can be functionally exchanged by its homolog from E. coli. A transcriptional and translational analysis of S. meliloti hfq expression by means of lacZ reporter fusions strongly suggests that the S. meliloti Hfq protein autocontrols its expression at the translational level, a phenomenon that was evident in the natural host S. meliloti as well as in the heterologous host E. coli.


Developing cognitive-emotional training exercises as interventions for mood and anxiety disorders.
There is an urgent need for more effective treatments for mood and anxiety disorders. As our understanding of the cognitive and affective neuroscience underlying psychiatric disorders expands, so do opportunities to develop novel interventions that capitalize on the capacity for brain plasticity. Cognitive training is one such strategy. This paper provides the background and rationale for developing cognitive-emotional training exercises as an intervention strategy, and proposes guidelines for the development and evaluation of cognitive training interventions with a specific focus on major depressive disorder as an example.


Reflection: one journey, two deaths, multiple perspectives.
This is a reflective piece from the author around death and dying. It shares her personal story from her own and close family perspectives. It then summaries these experiences into a few key themes and what she hopes are some lessons for doctors involved in the care of a dying person and their whānau.


Temperature and Pressure Dependences of the Elastic Properties of Tantalum Single Crystals Under <100> Tensile Loading: A Molecular Dynamics Study.
Atomistic simulations are capable of providing insights into physical mechanisms responsible for mechanical properties of the transition metal of Tantalum (Ta). By using molecular dynamics (MD) method, temperature and pressure dependences of the elastic properties of Ta single crystals are investigated through <100> tensile loading. First of all, a comparative study between two types of embedded-atom method (EAM) potentials is made in term of the elastic properties of Ta single crystals. The results show that Ravelo-EAM (Physical Review B, 2013, 88: 134101) potential behaves well at different hydrostatic pressures. Then, the MD simulation results based on the Ravelo-EAM potential show that Ta will experience a body-centered-cubic (BCC) to face-centered-cubic (FCC) phase transition before fracture under <100> tensile loading at 1 K temperature, and model size and strain rate have no obvious effects on tensile behaviors of Ta. Next, from the simulation results at the system temperature from 1 to 1500 K, it can be derived that the elastic modulus of E100 linearly decrease with the increasing temperature, while the yielding stress decrease with conforming a quadratic polynomial formula. Finally, the pressure dependence of the elastic properties is performed from 0 to 140 GPa and the observations show that the elastic modulus increases with the increasing pressure overall.


[Chronic pain in pediatric primary care : What do adolescents and parents expect and how do they perceive treatment?]
Recurrent pain in childhood and adolescence is a common health problem. Pediatricians are usually the patients' first contact person. The current study investigated patients' and parents' expectations when consulting a pediatrician and their rating of the treatment. In 36 pediatric practices, 224 patients with recurrent pain and 273 parents participated in this cross-sectional tablet survey. The collected data included the motivation for arranging a physician consultation, pain concept, treatment expectations, and assessment of treatment. Additionally, the patients' age was investigated as an influencing factor. The patients' and parents' predominant motivation for arranging a consultation was the clarification of the cause of pain. Older patients were additionally motivated by frequent but ineffective drug use. Predominantly in older patients, a biopsychosocial pain explanation was identified. Approximately half of all patients and parents indicated biological and psychological influencing factors. The most frequent expectation of the consultation was obtaining information on pain management. Overall, consultations were rated very positively, especially when patients and parents felt understood and taken seriously. Information about the cause of pain and pain management are essential for patients and parents. Besides good communication, sufficient time resources of the practitioner are required.


Prevalence and expression of familial combined hyperlipidemia in childhood.
The objectives of this study were (1) to determine the incidence of dominantly inherited hyperlipoproteinemia in children referred to our medical center because of hyperlipidemia associated with a family history of premature coronary artery disease and (2) to assess the degree of expression in childhood of the most common inherited hyperlipoproteinemia, familial combined hyperlipidemia. Among 129 families referred to us by area pediatricians, we identified a dominantly inherited hyperlipoproteinemia in 97 of them. Twenty had familial hypercholesterolemia, 65 familial combined hyperlipidemia, 11 hyperapobetalipoproteinemia, and one familial hypertriglyceridemia. As expected, almost half (9/20) of the siblings of probands with familial hypercholesterolemia were affected. Although we expected incomplete gene penetrance in the siblings of the probands with familial combined hyperlipidemia, we found 43 affected and 40 unaffected among the 83 siblings of the 65 probands. Our findings suggest that hyperlipidemia in children, caused by familial combined hyperlipidemia, occurs more than three times as frequently as familial hypercholesterolemia and that in families identified by a child proband, the penetrance is complete. Pediatricians should identify this primary hyperlipidemia in childhood and attempt to prevent the associated risk of premature coronary artery disease by prescribing appropriate diet and life-style modifications.


Effect of tritiated thymidine on the kinetics and viability of 9L cells in vitro.
The colony-forming efficiency of 9L rat gliosarcoma cells was unaffected by treatment with 0.1 muCi/ml of [3H]TdR. However, when cells were treated with 1 or 10 muCi/ml of [3H]Tdr, cell growth was reduced and cell survival decreased. When monolayer 9L cells were treated with 1 muCi/ml of [3H]TdR for up to 72 hr, approximately 5% survived, which is closely related to the percentage of non-cycling cells in this system. When cells were treated with 10 muCi/ml of [3H]TdR for 72 hr, less survival was observed. The additional cell kill observed may be induced by [3H]TdR released from doomed cells into petri dishes during the incubation period of the colony-formation assay.