[Fat-emulsions and acid-base balance in neonates of low weight at birth (author's transl)].
The influence of a single intravenous infusion of triglycerides (1 g triglyceride per kg body weight) on the acid base equilibrium was investigated in 16 newborn infants with low birth weight during the first days of age. No changes of pH, PCO2 and standard bicarbonate, base excess, buffer base and actuelle bicarbonate, respectively, were observed. Fat emulsions can be used, therefore, without hazards in the parenteral feeding of newborn infants.


Local dissipation and coupling properties of cellular oscillators: a case study on calcium oscillations.
Synchronised signal transduction between cells is crucial, since it assures fast and immutable information processing, which is vital for flawless functioning of living organisms. The question arises how to recognise the ability of a cell to be easily coupled with other cells. In the present paper, we investigate the system properties that determine best coupling abilities and assure the most efficient signal transduction between cells. A case study is done for intercellular calcium oscillations. For a particular diffusion-like coupled system of cellular oscillators, we determined the minimal gap-junctional permeability that is necessary for synchronisation of initially asynchronous oscillators. Our results show that dissipation is a crucial system property that determines the coupling ability of cellular oscillators. We found that low dissipation assures synchronisation of coupled cells already at very low gap-junctional permeability, whereas highly dissipative oscillators require much higher gap-junctional permeability in order to synchronise. The results are discussed in the sense of their biological importance for systems where the synchronous responses of cells were recognised to be indispensable for appropriate physiological functioning of the tissue.


Selective neurodegeneration generated by intravenous α-synuclein pre-formed fibril administration is not associated with endogenous α-synuclein levels in the rat brain.
Selective loss of discrete neuronal populations is a prominent feature of many neurodegenerative conditions, but the molecular basis of this is poorly understood. A central role of α-synuclein in the selective neurodegeneration of Parkinson's disease has been speculated, as its level of expression critically determines the propensity of this protein to misfold. To investigate whether the propensity of neuronal cell loss is associated with the level of endogenous α-synuclein expression, non-transgenic rats were given a single intravenous administration of α-synuclein pre-formed fibrils (PFFs) reversibly complexed with the rabies virus glycoprotein peptide (RVG9R). The number of surviving cells in different neuronal populations was systematically quantified using unbiased stereology. Our data demonstrated that a non-selective, transvascular delivery of α-synuclein PFFs led to a time-dependent loss of specific populations of midbrain (but not olfactory) dopaminergic neurons, medullary (but not pontine) cholinergic neurons, and brainstem serotonergic neurons. Contrary to the central role of endogenous α-synuclein expression in determining the seeding and aggregation propensity of pathological α-synuclein, we did not observe an association between the levels of α-synuclein expression in different regions of the rodent brain (although did not ascertain this at the individual cell level) and neurodegenerative propensity. The results from our study highlight the complexity of the neurodegenerative process generated by α-synuclein seeding. Further investigations are therefore required to elucidate the molecular basis of neurodegeneration driven by exogenous pathogenic α-synuclein spread.


Seed weight and seed resources in relation to plant growth rate.
Relative growth rate in radish is not influenced by initial seed weight.


The rate of absorption and relative bioavailability of caffeine administered in chewing gum versus capsules to normal healthy volunteers.
The purpose of this study was to evaluate the rate of absorption and relative bioavailability of caffeine from a Stay Alert chewing gum and capsule formulation. This was a double blind, parallel, randomized, seven treatment study. The treatment groups were: 50, 100, and 200 mg gum, 50, 100, and 200 mg capsule, and a placebo. Subjects consisted of 84 (n=12 per group); healthy, non-smoking, males who had abstained from caffeine ingestion for at least 20 h prior to dosing and were randomly assigned to the treatment groups. Blood samples were collected pre-dose and at 5, 15, 25, 35, 45, 55, 65, 90 min and 2, 3, 4, 6, 8, 12, 16 and 29 h post administration. Plasma caffeine levels were analyzed by a validated UV-HPLC method. Mean Tmax for the gum groups ranged from 44.2 to 80.4 min as compared with 84.0-120.0 min for the capsule groups. The Tmax, for the pooled data was significantly lower (P<0.05) for the gum groups as compared with the capsule groups. Differences in Tmax were significant for the 200 mg capsule versus 200 mg gum (P<0.05). The mean ka values for the gum group ranged from 3.21 to 3.96 h-1 and for the capsule groups ranged from 1.29 to 2.36 h-1. Relative bioavailability of the gum formulation after the 50, 100 and 200 mg dose was 64, 74 and 77%, respectively. When normalized to the total drug released from the gum (85%), the relative bioavailability of the 50, 100 and 200 mg dose were 75, 87, and 90%, respectively. No statistical differences were found for Cmax and AUCinf for comparisons of the gum and capsule formulations at each dose. Within each dose level, there were no significant formulation related differences in Cmax. No significant differences were observed in the elimination of caffeine after the gum or capsule. The results suggest that the rate of drug absorption from the gum formulation was significantly faster and may indicate absorption via the buccal mucosa. In addition, for the 100 and 200 mg groups, the gum and capsule formulations provide near comparable amounts of caffeine to the systemic circulation. These findings suggest that there may be an earlier onset of pharmacological effects of caffeine delivered as the gum formulation, which is advantageous in situations where the rapid reversal of alertness and performance deficits resulting from sleep loss is desirable.


Preclinical evaluation of performance, safety and usability of VAX-ID®, a novel intradermal injection device.
The recent SARS-Cov2 pandemic and mpox health emergency have led to renewed interest in intradermal vaccination due to its dose sparing potential. Indeed, intradermal vaccination is particularly of interest for use in mass vaccination campaigns, pandemic preparedness programs, and/or for vaccines that are expensive or in short supply. Moreover, the rich immune network in the skin makes it an attractive target not only for prophylactic vaccination, but also for therapeutic vaccination, like immunotherapy and (dendritic) cell-based therapies. The aim of the current paper was to provide an overview of preclinical data generated with VAX-ID®, a novel intradermal drug delivery device, to allow assessing it performance, safety and usability. The device can overcome challenges seen with the Mantoux technique whereby the needle needs to be inserted under a shallow angle. Various parameters of VAX-ID® were evaluated, including dead-space volume, dose accuracy, penetration depth & liquid deposit in piglets, as well as usability by healthcare professionals. The device has shown to have a low dead volume and a high dose accuracy. Importantly, the device performed successful injections at a predefined depth into the dermis with a high safety profile as confirmed by visual and histological evaluation in piglets. Moreover, the device was rated as easy to use by healthcare professionals. The combined preclinical performance and usability findings indicate that VAX-ID® can provide reliable, standardized and accurate drug delivery in the dermal layer of the skin with a high ease of use. The device offers a solution for injection of various prophylactic as well as therapeutic vaccines.


Biofield Frequency Bands-Definitions and Group Differences.
In the biofield literature, it is suggested that electromagnetic energy is part of the biofield. However, little is known about the exact definition of potential electromagnetic biofield frequency bands (FBs).Primary Study Objective: The current study sought to identify biofield FBs and test potential group differences.Methods/Design: High-frequency (i.e. >200 Hertz) voltage was measured at body parts along the spine and the brain. Measurements were conducted in an electrically shielded laboratory. Twenty experienced biofield practitioners (BPs, sample 1) and twenty-four students (STs, sample 2) participated in the study. The BPs performed a wide set of biofield exercises, while the STs participated in an assessment centre (with exercises such as role play). A total of N = 342 exercises were performed.Primary Outcome Measures: Based on surface electromyography, high-frequency (i.e., >200 Hertz) voltage was utilized as outcome measure. 10 FBs were identified across all the data sets. The BPs had higher spectral power across these bands compared to the STs. The present paper presents a replicable method for the assessment of electromagnetic FBs which are potentially useful for future biofield research.


Global drivers of eukaryotic plankton biogeography in the sunlit ocean.
Eukaryotic plankton are a core component of marine ecosystems with exceptional taxonomic and ecological diversity, yet how their ecology interacts with the environment to drive global distribution patterns is poorly understood. In this work, we use Tara Oceans metabarcoding data, which cover all major ocean basins, combined with a probabilistic model of taxon co-occurrence to compare the biogeography of 70 major groups of eukaryotic plankton. We uncover two main axes of biogeographic variation. First, more-diverse groups display clearer biogeographic patterns. Second, large-bodied consumers are structured by oceanic basins, mostly through the main current systems, whereas small-bodied phototrophs are structured by latitude and follow local environmental conditions. Our study highlights notable differences in biogeographies across plankton groups and investigates their determinants at the global scale.


COVID-19 vicarious traumatization links functional connectome to general distress.
As characterized by repeated exposure of others' trauma, vicarious traumatization is a common negative psychological reaction during the COVID-19 pandemic and plays a crucial role in the development of general mental distress. This study aims to identify functional connectome that encodes individual variations of pandemic-related vicarious traumatization and reveal the underlying brain-vicarious traumatization mechanism in predicting general distress. The eligible subjects were 105 general university students (60 females, aged from 19 to 27 years) undergoing brain MRI scanning and baseline behavioral tests (October 2019 to January 2020), whom were re-contacted for COVID-related vicarious traumatization measurement (February to April 2020) and follow-up general distress evaluation (March to April 2021). We applied a connectome-based predictive modeling (CPM) approach to identify the functional connectome supporting vicarious traumatization based on a 268-region-parcellation assigned to network memberships. The CPM analyses showed that only the negative network model stably predicted individuals' vicarious traumatization scores (q2 = -0.18, MSE = 617, r [predicted, actual] = 0.18, p = 0.024), with the contributing functional connectivity primarily distributed in the fronto-parietal, default mode, medial frontal, salience, and motor network. Furthermore, mediation analysis revealed that vicarious traumatization mediated the influence of brain functional connectome on general distress. Importantly, our results were independent of baseline family socioeconomic status, other stressful life events and general mental health as well as age, sex and head motion. Our study is the first to provide evidence for the functional neural markers of vicarious traumatization and reveal an underlying neuropsychological pathway to predict distress symptoms in which brain functional connectome affects general distress via vicarious traumatization.


Acute bilateral lower extremity arterial occlusion without risk factors or embolic source.
Acute arterial occlusion is an emergency condition that, if untreated, can lead to serious complications and potential limb amputation. Risk factors for acute arterial occlusion include aortic atherosclerosis, arterial trauma, recent myocardial infarction, and atrial fibrillation. We present a patient with no history of peripheral vascular disease who presented to the emergency department with severe bilateral leg pain. Computed tomography angiography was performed showing bilateral acute arterial occlusions. Emergent vascular surgery was performed to remove the thrombus and establish perfusion in order to prevent bilateral lower leg amputation.


A calcium-dependent mechanism for associating a soluble arachidonoyl-hydrolyzing phospholipase A2 with membrane in the macrophage cell line RAW 264.7.
Arachidonoyl-hydrolyzing phospholipase A2 plays a central role in providing substrate for the synthesis of the potent lipid mediators of inflammation, the eicosanoids, and platelet-activating factor. Although Ca2+ is required for arachidonic acid release in vivo and most phospholipase A2 enzymes require Ca2+ for activity in vitro, the role of Ca2+ in phospholipase A2 activation is not understood. We have found that an arachidonoyl-hydrolyzing phospholipase A2 from the macrophage-like cell line, RAW 264.7, exhibits Ca2(+)-dependent association with membrane. The intracellular distribution of the enzyme was studied as a function of the Ca2+ concentration present in homogenization buffer. The enzyme was found almost completely in the 100,000 x g soluble fraction when cells were homogenized in the presence of Ca2+ chelators and there was a slight decrease in soluble fraction activity when cells were homogenized at the level of Ca2+ in an unstimulated cell (80 nM). When cells were homogenized at Ca2+ concentrations expected in stimulated cells (230-450 nM), 60-70% of the phospholipase A2 activity was lost from the soluble fraction and became associated with the particulate fraction in a manner that was partly reversible with EGTA. Membrane-associated phospholipase A2 activity was demonstrated by [3H]arachidonic acid release both from exogenous liposomes and from radiolabeled membranes. With radiolabeled particulate fraction as substrate, this enzyme hydrolyzed arachidonic acid but not oleic acid from membrane phospholipid, and [3H]arachidonic acid was derived from phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol/phosphatidylserine. We suggest a mechanism in which the activity of phospholipase A2 is regulated by Ca2+: in an unstimulated cell phospholipase A2 is found in the cytosol; upon receptor ligation the cytosolic Ca2+ concentration increases, and the enzyme becomes membrane-associated which facilitates arachidonic acid hydrolysis.


Recent applications of molecular imprinted polymers for enantio-selective recognition.
Molecular imprinted polymer (MIP) techniques have been increasingly used in a variety of fields including chromatography, sample pretreatment, purification, sensors, drug delivery, and catalysts, etc. MIP is a specific artificial receptor that shows favored affinity to the template molecule. The cavities of the template are produced by carrying out polymerization of a reaction mixture followed by eliminating the template molecules by washing. Various forms of MIP materials have been prepared for diverse applications including irregularly ground particles, regular spherical particles, nanoparticles, monoliths in a stainless steel or capillary column, open tubular layers in capillaries, membranes, surface attached thin layers, and composites, etc. When an enantiomer is used as the template, then the resulting MIP can show capability of enantiomeric recognition between the pair of enantiomers. In this review, progresses in applications of enantio-selective recognition by MIPs will be critically reviewed for the recent period since 2007.


Awareness and Attitude toward the Replacement of Missing Teeth among Patients at a Dental Institute: A Cross-sectional Study.
To evaluate the awareness among the patients visiting a dental college in replacing the missing teeth. A cross-sectional survey was conducted to know the patient's awareness and preference for the treatment options. A list of the closed-ended questionnaire was used to record the patient's response about being edentulous. The collected data were statistically analyzed. SPSS, Version 2.1, statistical software was used. The descriptive statistics were done using frequency and percentage. Bar graphs and pie graphs were used wherever applicable. Maximum patients reported to dental treatment with less than 1 year period of edentulousness. This directly indicates an increased awareness among the patients (77.5%). The need to replace the missing teeth was a function such as mastication of food for 42.6% of the patients and 36.6% of the patients wanted to replace their missing teeth for improving their appearance. The most preferred method of the replacement is fixed partial denture (FPD) as it was cost-effective and affordable for them. Only 22% of the patients wanted an implant as a treatment option as it did not involve the adjacent teeth. The awareness and knowledge about the treatment options among the patients visiting the dental college have increased, but still, the awareness about the consequences of being edentulous for a long time should be improved through social media by the dentists. The replacement of missing teeth is important in rehabilitating the form, function, esthetics, and integrity of the stomatognathic system. There are various treatment options available for replacing missing teeth. Very few patients are aware of all the options and the consequences of not replacing the posterior teeth.


Histoenzymological mapping of alkaline phosphatase and 5-nucleotidase in the medulla oblongata of a microchiropteran bat (Taphozous melanopogon Temminck).
The contribution deals with the distribution of alkaline phosphatase and 5-nucleotidase in the medulla oblongata of Taphozous melanopogon (a Microchiroptera), for the first time. The main highlights of the study are: (1) Cranial nerve nuclei demonstrate intense activity of alkaline phosphatase, whereas except nucleus tractus spinalis n. trigemini, rest of the nuclei show much variations of 5-nucleotidase distribution. (2) The vestibular nuclei are very intensely positive for 5-nucleotidase but exhibit variable activity of alkaline phosphatase. (3) Three subdivisions of nucleus olivaris inferior, i.e. nucleus olivaris accessorius medialis, nucleus olivaris accessorius dorsalis and nucleus olivaris inferior, which were not reported in the earlier neuroanatomical studies, have been identified. These nuclei show very intense alkaline phosphatase and relatively less intense 5-nucleotidase activities. (4) In general, the activity of alkaline phosphatase is stronger in neurons than in neuropil and that of 5-nucleotidase is stronger in neuropil than in neurons. (5) Blood capillaries are completely negative for alkaline phosphatase and intensely positive for 5-nucleotidase. A comparison is made between the distribution of these enzymes in the medulla oblongata of bat and other mammals so far studied.


Controlled dual delivery of fibroblast growth factor-2 and Interleukin-10 by heparin-based coacervate synergistically enhances ischemic heart repair.
Myocardial infarction (MI) causes myocardial necrosis, triggers chronic inflammatory responses, and leads to pathological remodeling. Controlled delivery of a combination of angiogenic and immunoregulatory proteins may be a promising therapeutic approach for MI. We investigated the bioactivity and therapeutic potential of an injectable, heparin-based coacervate co-delivering an angiogenic factor, fibroblast growth factor-2 (FGF2), and an anti-inflammatory cytokine, Interleukin-10 (IL-10) in a spatially and temporally controlled manner. Coacervate delivery of FGF2 and IL-10 preserved their bioactivities on cardiac stromal cell proliferation in vitro. Upon intramyocardial injection into a mouse MI model, echocardiography revealed that FGF2/IL-10 coacervate treated groups showed significantly improved long-term LV contractile function and ameliorated LV dilatation. FGF2/IL-10 coacervate substantially augmented LV myocardial elasticity. Additionally, FGF2/IL-10 coacervate notably enhanced long-term revascularization, especially at the infarct area. In addition, coacervate loaded with 500 ng FGF2 and 500 ng IL-10 significantly reduced LV fibrosis, considerably preserved infarct wall thickness, and markedly inhibited chronic inflammation at the infarct area. These results indicate that FGF2/IL-10 coacervate has notably greater therapeutic potential than coacervate containing only FGF2. Overall, our data suggest therapeutically synergistic effects of FGF-2/IL-10 coacervate, particularly coacervate with FGF2 and 500 ng IL-10, for the treatment of ischemic heart disease.


AHR-dependent misregulation of Wnt signaling disrupts tissue regeneration.
The origins of molecular toxicology can be traced to understanding the interactions between halogenated aromatic hydrocarbons and the aryl hydrocarbon receptor (AHR). The physiological consequences of activation of the aryl hydrocarbon receptor are diverse, and we are just beginning to understand the importance of the AHR signal transduction pathway in homeostasis and disease. The many downstream targets that mediate these biological responses remain undefined. Studies have exploited the power of the zebrafish model to elucidate the mechanisms by which AHR activation disrupts biological signaling. Recent genomic analysis performed in a zebrafish tissue regeneration model revealed functional cross talk between AHR and the well-established Wnt/beta-catenin signal transduction pathway. This review focuses on the development of the zebrafish model of AHR biology and the application of in vivo toxicogenomics to unravel molecular mechanisms.


Imaging of experimental rat gliomas using a clinical MR scanner.
Studies of brain tumor development in experimental animal models have to date mostly been based on post-mortem histological examinations. The use of magnetic resonance imaging (MRI) may provide a non-invasive technique for studying tumor growth and treatment effects in such animal models. However, most of these studies have been performed on purpose-dedicated small bore magnetic resonance (MR) systems, of high cost and limited availability. The purpose of this study was thus to obtain high-resolution images of experimental gliomas in the rat brain, using a clinical 1.5 T MR scanner. Anesthesized rats bearing BT4C brain tumors were positioned into a specially designed immobilizing device, and a small circular coil was positioned onto the skulls. Two T1 weighted series were acquired before and after subcutaneous contrast injections. A T2 weighted series was also obtained. The rats were then sacrified, the brains removed, and the histological tumor volumes were compared to the volumes obtained on MRI. There were visible tumors in 10 of 13 animals scanned on MR. The rim of the tumors were visualized on T1 weighted series without contrast. On T1 images with contrast, the tumors were seen as high signal intensity areas. The T2 weighted images showed peritumoral edema. No necrosis or cystic parts of the tumors were detected. There was a consistency between the MR and the histology findings, showing a high degree of correlation between the two volume determination methods. High-resolution images of experimental rat gliomas can be obtained using a clinical MR scanner and a commercially available RF coil. This MRI technique may also be expanded to extraneural rat tumor models, for studies of tumor development and treatment.


Daily caloric restriction limits tumor growth more effectively than caloric cycling regardless of dietary composition.
Cancer incidence increases with age and is a leading cause of death. Caloric restriction (CR) confers benefits on health and survival and delays cancer. However, due to CR's stringency, dietary alternatives offering the same cancer protection have become increasingly attractive. Short cycles of a plant-based diet designed to mimic fasting (FMD) are protective against tumorigenesis without the chronic restriction of calories. Yet, it is unclear whether the fasting time, level of dietary restriction, or nutrient composition is the primary driver behind cancer protection. Using a breast cancer model in mice, we compare the potency of daily CR to that of periodic caloric cycling on FMD or an isocaloric standard laboratory chow against primary tumor growth and metastatic burden. Here, we report that daily CR provides greater protection against tumor growth and metastasis to the lung, which may be in part due to the unique immune signature observed with daily CR.


Localized Multi-Site Knee Bioimpedance as a Predictor for Knee Osteoarthritis Associated Pain Within Older Adults During Free-Living.
The drastic increase in the aging population has increased the prevalence of osteoarthritis in the United States. The ability to monitor symptoms of osteoarthritis (such as pain) within a free-living environment could improve understanding of each person's experiences with this disease and provide opportunities to personalize treatments specific to each person and their experience. In this work, localized knee tissue bioimpedance and self-reports of knee pain were collected from older adults ([Formula: see text]) with and without knee osteoarthritis over 7 days of free-living to evaluate if knee tissue bioimpedance is associated with persons' knee pain experience. Within the group of persons' with knee osteoarthritis increases in 128 kHz per-length resistance and decreases in 40 kHz per-length reactance were associated with increased probability of persons having active knee pain ([Formula: see text] and [Formula: see text]).


Curcumin reduces paclitaxel resistance in ovarian carcinoma cells by upregulating SNIP1 and inhibiting NFκB activity.
The therapeutic activity of paclitaxel against ovarian carcinoma is relatively low due to the frequent occurrence of chemoresistance and disease recurrence. We found earlier that a combination of curcumin and paclitaxel reduces cell viability and promotes apoptosis in paclitaxel-resistant (i.e., taxol-resistant, Txr) ovarian cancer cells. In the present study, we first used RNA sequencing (RNAseq) analysis to identify genes that are upregulated in Txr cell lines but downregulated by curcumin in ovarian cancer cells. The nuclear factor kappa B (NFκB) signaling pathway was shown to be upregulated in Txr cells. Furthermore, based on the protein interaction database BioGRID, we found that Smad nuclear interacting protein 1 (SNIP1) may be involved in regulating the activity of NFκB in Txr cells. Accordingly, curcumin upregulated SNIP1 expression, which in turn downregulated the pro-survival genes Bcl-2 and Mcl-1. Using shRNA-guided gene silencing, we found that SNIP1 depletion reversed the inhibitory effect of curcumin on NFκB activity. Moreover, we identified that SNIP1 enhanced NFκB protein degradation, thereby suppressing NFκB/p65 acetylation, which is involved in the inhibitory effect of curcumin on NFκB signaling. The transcription factor early growth response protein 1 (EGR1) was shown to represent an upstream transactivator of SNIP1. Consequently, we show that curcumin inhibits NFκB activity by modulating the EGR1/SNIP1 axis to attenuate p65 acetylation and protein stability in Txr cells. These findings provide a new mechanism to account for the effects of curcumin in inducing apoptosis and reducing paclitaxel resistance in ovarian cancer cells.


Statistical parametric mapping of immunopositive cell density.
We developed a new method for comparing immunopositive cell densities across groups of animals and creating statistical parametric maps on standardized sections. As an example, we compared Iba-1 (microglial marker) positive cell densities in rats with (n=6) and without (n=6) unilateral injection of 1-methyl-4-phenylpyridinium salt (MPP+). Immunopositive cells were automatically counted in each animal over a coronal section in the midbrain (bregma -5.9 mm) and a positive cell density map was created for each animal. After the positive cell density map was normalized to a template section from an atlas, positive cell densities of the two groups were compared in each pixel over the section and a statistical parameter (p-value from t-test) was mapped on each pixel. We were able to detect significant increases of microglias in the side of MPP+ injection not only in the substantia nigra pars compacta but also in adjacent white matter. We also applied the same analysis to tyrosine hydroxylase stained sections and detected significant decreases of dopamine neurons in the side of MPP+ injection. The new method was proven to be useful for detecting significant changes of cell densities over the entire area of immunostained sections.


The psychiatric educational experiences of advance beginner RNs.
The nursing profession is in an extraordinary position to improve educational experiences of prospective nurses, particularly within psychiatric nursing. To acquire an enhanced understanding of the nurse's instructive learning process and skills regarding psychiatric nursing, this study described and explored the experiences of advance beginner nurses employed in mental health facilities. It also denoted the registered nurses' (RNs) educational preparedness to function in their new professional role. Reflection of the nurse's personal experiences was acquired by using a qualitative study with a phenomenological approach. Colaizzi's Frame work [Colaizzi, P., 1978. Psychological research as the phenomenologist views it. In: Valle, R., King, M. (Eds.), Existential Phenomenological Alternative for Psychology. Oxford University Press, NY, pp. 48-71] guided the mode of data analysis by enlisting 15 advance beginner nurses to participate in in-depth, audio-taped interviews. Results from this study indicated a need for educational improvements to accurately reflect trends of psychiatric patient care in order to emphasize interpersonal relationships as well as multi-diagnosis and co-morbidity. Additionally, increased contact with diverse patient populations and responsibilities congruent with other clinical placements in managing the patient's overall care were noted to be critical. This study suggests that some nursing educational programs can improve their curriculum, methods of teaching and approach used to introduce students to psychiatric mental health nursing.


Ontario appellate court overturns judgment for plaintiffs infected through tainted blood.
On 29 November 2001, the Ontario Court of Appeal issued a lengthy decision overturning a lower-court judgment in favour of three hemophiliacs infected with HIV in 1985 through contaminated blood-factor concentrate. The joint decision in the three cases of Robb, Rintoul, and Farrow is the latest decision in litigation dating back to 1992. The plaintiffs alleged negligence by the Canadian Red Cross Society and the Canadian government for delays in introducing heat-treated concentrate after the risks posed by unheated product were known.


[Neisseria gonorrhoeae: antimicrobial resistance and study of population dynamics. Situation in Barcelona in 2011].
Due to the high rates of antimicrobial resistance to certain antibiotics, together with the emergence of Neisseria gonorrhoeae (NG) with reduced susceptibility and resistance to third-generation cephalosporins, gonococcal infection is becoming a public health problem. The objectives of the study were: To keep track of the antimicrobial susceptibility of NG strains obtained from January to August 2011. To study the population dynamics. The antimicrobial susceptibility was studied by disk-diffusion and E-test. The genotyping was performed by NG-MAST method. Of a total of 100strains studied, 59% showed intermediate sensitivity to penicillin and 9% were resistant. According to EUCAST, we detected 3gonococci with reduced susceptibility to ceftriaxone, 10 to cefixime and one with high-level resistance to both antibiotics (MIC 1.5μg/ml). MIC50 and MIC90 to cefixime were 0.016 and 0.125μg/ml, respectively, whereas to ceftriaxone they were <0.016 and 0.064μg/ml, respectively. Almost all (99%) of the strains were resistant to doxycycline, 53% to ciprofloxacin, 3% to azithromycin, and 1% to spectinomycin. The most prevalent ST was ST1407, predominantly associated to resistance or reduced sensitivity to cephalosporins or macrolides. NG has developed significant rates of resistance to various antibiotics. One strain has been detected with high level resistance to third generation cephalosporins, and several strains with reduced susceptibility. An increase in MIC50 and MIC90 to these antibiotics has also been observed. NG population structure remains stable and common to the rest of Europe, although two new ST (ST7226 and ST7227) have been identified that could be selected and acquire high levels of resistance to cephalosporins.


Effect of mixing on reaction-diffusion kinetics for protein hydrogel-based microchips.
Protein hydrogel-based microchips are being developed for high-throughput evaluation of the concentrations and activities of various proteins. To shorten the time of analysis, the reaction-diffusion kinetics on gel microchips should be accelerated. Here we present the results of the experimental and theoretical analysis of the reaction-diffusion kinetics enforced by mixing with peristaltic pump. The experiments were carried out on gel-based protein microchips with immobilized antibodies under the conditions utilized for on-chip immunoassay. The dependence of fluorescence signals at saturation and corresponding saturation times on the concentrations of immobilized antibodies and antigen in solution proved to be in good agreement with theoretical predictions. It is shown that the enhancement of transport with peristaltic pump results in more than five-fold acceleration of binding kinetics. Our results suggest useful criteria for the optimal conditions for assays on gel microchips to balance high sensitivity and rapid fluorescence saturation kinetics.


Immune responses to Pneumocystis murina are robust in healthy mice but largely absent in CD40 ligand-deficient mice.
Pneumocystis is a pathogen of immunocompromised hosts but can also infect healthy hosts, in whom infection is rapidly controlled and cleared. Microarray methods were used to examine differential gene expression in the lungs of C57BL/6 and CD40 ligand knockout (CD40L-KO) mice over time following exposure to Pneumocystis murina. Immunocompetent C57BL/6 mice, which control and clear infection efficiently, showed a robust response to infection characterized by the up-regulation of 349 primarily immune response-associated genes. Temporal changes in the expression of these genes identified an early (Week 2), primarily innate response, which waned before the infection was controlled; this was followed by primarily adaptive immune responses that peaked at Week 5, which coincided with clearance of the infection. In conjunction with the latter, there was an increased expression of B cell-associated (Ig) genes at Week 6 that persisted through 11 weeks. In contrast, CD40L-KO mice, which are highly susceptible to developing severe Pneumocystis pneumonia, showed essentially no up-regulation of immune response-associated genes at Days 35-75. Immunohistochemical staining supported these observations by demonstrating an increase in CD4+, CD68+, and CD19+ cells in C57BL/6 but not CD40L-KO mice. Thus, the healthy host demonstrates a robust, biphasic response to infection by Pneumocystis; CD40L is an essential upstream regulator of the adaptive immune responses that efficiently control infection and prevent development of progressive pneumonia.


Stationary status of discrete and continuous age-structured population models.
From Leonhard Euler to Alfred Lotka and in recent years understanding the stationary process of the human population has been of central interest to scientists. Population reproductive measure NRR (net reproductive rate) has been widely associated with measuring the status of population stationarity and it is also included as one of the measures in the millennium development goals. This article argues how the partition theorem-based approach provides more up-to-date and timely measures to find the status of the population stationarity of a country better than the NRR-based approach. We question the timeliness of the value of NRR in deciding the stationary process of the country. We prove associated theorems on discrete and continuous age distributions and derive measurable functional properties. The partitioning metric captures the underlying age structure dynamic of populations at or near stationarity. As the population growth rates for an ever-increasing number of countries trend towards replacement levels and below, new demographic concepts and metrics are needed to better characterize this emerging global demography.


MBGA-Net: A multi-branch graph adaptive network for individualized motor imagery EEG classification.
The development of deep learning has led to significant improvements in the decoding accuracy of Motor Imagery (MI) EEG signal classification. However, current models are inadequate in ensuring high levels of classification accuracy for an individual. Since MI EEG data is primarily used in medical rehabilitation and intelligent control, it is crucial to ensure that each individual's EEG signal is recognized with precision. We propose a multi-branch graph adaptive network (MBGA-Net), which matches each individual EEG signal with a suitable time-frequency domain processing method based on spatio-temporal domain features. We then feed the signal into the relevant model branch using an adaptive technique. Through an enhanced attention mechanism and deep convolutional method with residual connectivity, each model branch more effectively harvests the features of the related format data. We validate the proposed model using the BCI Competition IV dataset 2a and dataset 2b. On dataset 2a, the average accuracy and kappa values are 87.49% and 0.83, respectively. The standard deviation of individual kappa values is only 0.08. For dataset 2b, the average classification accuracies obtained by feeding the data into the three branches of MBGA-Net are 85.71%, 85.83%, and 86.99%, respectively. The experimental results demonstrate that MBGA-Net could effectively perform the classification task of motor imagery EEG signals, and it exhibits strong generalization performance. The proposed adaptive matching technique enhances the classification accuracy of each individual, which is beneficial for the practical application of EEG classification.


The potential of endophytic fungi isolated from cucurbit plants for biocontrol of soilborne fungal diseases of cucumber.
The ability of endophytic fungi isolated from cucurbit plants to suppress soilborne diseases and the relationship between antagonism and disease suppression were studied. In dual culture tests of 1044 strains of 90 genera and three pathogenic fungi, 47.1 % of the endophytic fungal strains showed antagonistic effects on at least one pathogen; 186 strains against Rhizoctonia solani, 371 strains against Sclerotinia sclerotiorum, and 403 strains against Fusarium oxysporum f. sp. cucumerinum. The main antagonistic type of the strains of one genus generally was identical to one pathogen. In the pot experiment of cucumber inoculated with R. solani and endophytic fungi, 74.3 % and 33.3 % of 288 strains showed control efficacy of more than 50 % and more than 80 % on cucumber Rhizoctonia root rot respectively. These strains were mostly distributed in Fusarium, Chaetomium, Colletotrichum and Acrocalymma. There were some differences in the proportion of strains with better disease suppressive effects between strain sources. No significant correlation existed between the disease suppression of a strain in vivo and its antagonism against the pathogen in vitro. Most growth-promoting strains had good suppressive effects on cucumber Rhizoctonia root rot. In this study, 82 endophytic fungal strains had good disease suppressive effects and no obvious adverse effects on cucumber growth, and 35 of them showed obvious growth-promoting effects, which suggested that endophytic fungi from cucurbit plants have excellent potential for plant disease control.


Feathers of the magpie (Pica pica) as a bioindicator material for heavy metal pollution assessment.
This study examined the lead and cadmium content of external tail feathers of magpies from 15 localities in Poland, differing in degree of industralization and urbanization. Extremely high levels (up to 1500 micrograms/g dry wt. Pb and about 40 micrograms/g dry wt. Cd) were found in samples from areas surrounding two zinc smelting works. The correlation between metal content in feathers and size of immission (mg/m2/y) at the sites of capture was 0.96 for Pb and 0.97 for Cd. Magpie tail feathers are recommended as a material for environmental biomonitoring.


pH-responsive magnetic biocompatible chitosan-based nanocomposite carrier for ciprofloxacin release.
The pH-sensitive and magnetic-triggered release ensures the effective delivery of drugs. Chitosan carries amine pendants that encourage the fabrication of pH-responsive carriers. Montmorillonite (MMt), an attractive nano-clay in drug delivery possessing high encapsulation properties, was magnetized through the co-precipitation of Fe3+/Fe2+ ions. The study aimed to integrate the magnetic montmorillonite (mMMt) into the chitosan matrix and crosslinked by citric acid (CA) to achieve the nanocomposite carrier with double-responsive features for effective drug delivery. The release evaluation revealed that coating the mMMt with CA-crosslinked chitosan prevented the burst release of Ciprofluxcacin (Cip). The nanocomposite showed a high sustained release, and the release rate in the neutral environment (pH 7.4) was remarkably higher than in acidic media (pH 5.8). The new nanocomposite carrier showed high encapsulation efficiency to Cip (about 98 %). The study was developed by investigating external magnetic effects on the release rate, which lead to an increase in the release rate. The kinetics studies confirmed the diffusion mechanism for Cip release in all experimental media. The Cip-loaded nanocomposite carriers showed antibacterial activity against E. coli and S. aureus.


Bioanalytical method development and validation for the determination of glycine in human cerebrospinal fluid by ion-pair reversed-phase liquid chromatography-tandem mass spectrometry.
A LC-MS/MS method has been developed and validated for the determination of glycine in human cerebrospinal fluid (CSF). The validated method used artificial cerebrospinal fluid as a surrogate matrix for calibration standards. The calibration curve range for the assay was 100-10,000ng/mL and (13)C2, (15)N-glycine was used as an internal standard (IS). Pre-validation experiments were performed to demonstrate parallelism with surrogate matrix and standard addition methods. The mean endogenous glycine concentration in a pooled human CSF determined on three days by using artificial CSF as a surrogate matrix and the method of standard addition was found to be 748±30.6 and 768±18.1ng/mL, respectively. A percentage difference of -2.6% indicated that artificial CSF could be used as a surrogate calibration matrix for the determination of glycine in human CSF. Quality control (QC) samples, except the lower limit of quantitation (LLOQ) QC and low QC samples, were prepared by spiking glycine into aliquots of pooled human CSF sample. The low QC sample was prepared from a separate pooled human CSF sample containing low endogenous glycine concentrations, while the LLOQ QC sample was prepared in artificial CSF. Standard addition was used extensively to evaluate matrix effects during validation. The validated method was used to determine the endogenous glycine concentrations in human CSF samples. Incurred sample reanalysis demonstrated reproducibility of the method.


[Nocardiosis as the first opportunistic disease in a patient with missed HIV infection. Pathomorphism of presentation, clinical course, and evolution].
It is reported on the ground of the most updated literature evidences an infrequent case of multiple cavitating pulmonary infiltrates and a probable liver abscess caused by a Nocardia asteroides disseminated infection heralding a HIV-related profound immunodeficiency who remained missed and undiagnosed until the emerging of this severe opportunistic infection.


Cone beam CT for perioperative imaging in hearing preservation Cochlear implantation - a human cadaveric study.
Knowledge of the cochlear implant array's precise position is important because of the correlation between electrode position and speech understanding. Several groups have provided recent image processing evidence to determine scalar translocation, angular insertion depth, and cochlear duct length (CDL); all of which are being used for patient-specific programming. Cone beam computed tomography (CBCT) is increasingly used in otology due to its superior resolution and low radiation dose. Our objectives are as followed: 1.Validate CBCT by measuring cochlear metrics, including basal turn diameter (A-value) and lateral wall cochlear duct length at different angular intervals and comparing it against microcomputed CT (uCT).2.Explore the relationship between measured lateral wall cochlear duct length at different angular intervals and insertion depth among 3 different length electrodes using CBCT. The study was performed using fixed human cadaveric temporal bones in a tertiary academic centre. Ten temporal bones were subjected to the standard facial recess approach for cochlear implantation and imaged by CBCT followed by uCT. Measurements were performed on a three-dimensional reconstructed model of the cochlea. Sequential insertion of 3 electrodes (Med-El Flex24, 28 and Soft) was then performed in 5 bones and reimaged by CBCT. Statistical analysis was performed using Pearson's correlation. There was good agreement between CBCT and uCT for cochlear metrics, validating the precision of CBCT against the current gold standard uCT in imaging. The A-value recorded by both modalities showed a high degree of linear correlation and did not differ by more than 0.23 mm in absolute values. For the measurement of lateral wall CDL at various points along the cochlea, there was a good correlation between both modalities at 360 deg and 720 deg (r = 0.85, p < 0.01 and r = 0.79, p < 0.01). The Flex24 electrode displayed consistent insertion depth across different bones. CBCT reliably performs cochlear metrics and measures electrode insertion depth. The low radiation dose, fast acquisition time, diminished metallic artifacts and portability of CBCT make it a valid option for imaging in cochlear implant surgery.


Four-dimensional HDlive rendering image of fetal facial expression: a pictorial essay.
Our objective was to present our experience of fetal facial expressions reconstructed employing the four-dimensional (4D) HDlive rendering mode. A total of 23 normal fetuses at 18-36 weeks' gestation were studied using the 4D HDlive rendering mode. The 4D HDlive rendering mode provided extraordinarily realistic features of the fetal face. In particular, blinking, mouthing, swallowing, yawning, tongue expulsion, and sucking were clearly noted. Moreover, various realistic fetal emotional expressions such as smiling-like and crying-like movements were recognized. The 4D HDlive rendered images of fetal facial expressions seem to be more readily discernible than those obtained by conventional 4D ultrasonography. Observation of facial expressions using the 4D HDlive rendering mode is considered to reflect the normal and abnormal neurological development of the fetus. Therefore, the 4D HDlive rendering mode may assist in evaluation of fetal brain function, and offer potential advantages relative to conventional 4D ultrasonography.


Gut Microbiota Profiles of Treated Metabolic Syndrome Patients and their Relationship with Metabolic Health.
Metabolic syndrome (MetS) has become a worldwide health issue. Recent studies reveal that the human gut microbiota exerts a significant role in the pathogenesis of this disease. While drug treatments may greatly improve metabolic symptoms, little is known about the gut microbiota composition of these treated MetS patients. This study aimed to characterize the gut microbiota composition of treated-MetS patients and analyse the possibility of using gut microbiota as an indicator of metabolic conditions. 16S rRNA metagenomic sequencing approach was used to profile gut microbiota of 111 treated MetS patients from The Cohort of patients at a high Risk of Cardiovascular Events (CORE)-Thailand registry. Our results show that the gut microbiota profiles of MetS patients are diverse across individuals, but can be classified based on their similarity into three groups or enterotypes. We also showed several associations between species abundance and metabolic parameters that are enterotype specific. These findings suggest that information on the gut microbiota can be useful for assessing treatment options for MetS patients. In addition, any correlations between species abundance and human properties are likely specific to each microbial community.


High-throughput interrogation of immune responses using the Human Immune Profiling Pipeline.
The current abundance of immunotherapy clinical trials presents an opportunity to learn about the underlying mechanisms and pharmacodynamic effects of novel drugs on the human immune system. Here, we present a protocol to study how these immune responses impact clinical outcomes using large-scale high-throughput immune profiling of clinical cohorts. We describe the Human Immune Profiling Pipeline, which comprises an end-to-end solution from flow cytometry results to computational approaches and unsupervised patient clustering based on lymphocyte landscape. For complete details on the use and execution of this protocol, please refer to Lyudovyk et al. (2022).1.


Potent and efficacious thienylamidine-incorporated thrombin inhibitors.
Novel thrombin inhibitors incorporating thienylamidine at the P1 position were designed and synthesized. These compounds are potent, trypsin-selective and efficacious in the rat model of venous thrombosis. The proposed P1 binding mode in the thrombin active site was confirmed by X-ray crystallographic analysis.


Bio-Kil, a nano-based disinfectant, reduces environmental bacterial burden and multidrug-resistant organisms in intensive care units.
This prospective before-after study was intended to investigate the effect of Bio-Kil on reducing environmental bacterial burden and healthcare-associated infections (HAIs) in intensive care units (ICUs) at the Municipal Wan-Fang Hospital, Taipei, Taiwan in 2014. Four rooms in the medical and surgical ICUs were investigated and designated as study rooms (n = 2) or control rooms (n = 2). Routine disinfection was performed during the pre-intervention period in both room types. Bio-Kil was applied to the fomites and surroundings of the study rooms during the intervention period. Total bacterial burden and proportion of colonization of fomites and surroundings by multidrug-resistance organisms (MDROs) were determined before and after the intervention. The demographic characteristics, underlying conditions, and clinical outcomes of patients were analyzed. After application of Bio-Kil, the bacterial burden declined in both groups, although the reduction was greater in the study rooms as compared with the control rooms (p = 0.001). During the pre-intervention period, 16 patients were admitted to control rooms and 18 patients to study rooms. After the intervention, 22 patients were admitted to control rooms and 21 patients to study rooms. The number of cases of new-onset sepsis declined in the intervention group (from 33% to 23.8%), but increased in the control group (from 25% to 40.9%); however, there was no significant difference in incidence of new-onset sepsis between the study and control rooms after intervention. Application of Bio-Kil reduced the environmental bacterial burden and MDROs in ICUs. Further studies are needed to evaluate the efficacy of this nanotechnology-based disinfectant in reducing HAIs.


Increased rate of missense/in-frame mutations in individuals with NF1-related pulmonary stenosis: a novel genotype-phenotype correlation.
Neurofibromatosis type 1 (NF1) and its related disorders (NF1-Noonan syndrome (NFNS) and Watson syndrome (WS)) are caused by heterozygous mutations in the NF1 gene. Pulmonary stenosis (PS) occurs more commonly in NF1 and its related disorders than in the general population. This study investigated whether PS is associated with specific types of NF1 gene mutations in NF1, NFNS and WS. The frequency of different NF1 mutation types in a cohort of published and unpublished cases with NF1/NFNS/WS and PS was examined. Compared with NF1 in general, NFNS patients had higher rates of PS (9/35=26% vs 25/2322=1.1%, P value<0.001). Stratification according to mutation type showed that the increased PS rate appears to be driven by the NFNS group with non-truncating mutations. Eight of twelve (66.7%) NFNS cases with non-truncating mutations had PS compared with a 1.1% PS frequency in NF1 in general (P<0.001); there was no increase in the frequency of PS in NFNS patients with truncating mutations. Eight out of eleven (73%) individuals with NF1 and PS, were found to have non-truncating mutations, a much higher frequency than the 19% reported in NF1 cohorts (P<0.015). Only three cases of WS have been published with intragenic mutations, two of three had non-truncating mutations. Therefore, PS in NF1 and its related disorders is clearly associated with non-truncating mutations in the NF1 gene providing a new genotype-phenotype correlation. The data indicate a specific role of non-truncating mutations on the NF1 cardiac phenotype.


Basophil activation testing.
Both the treatment of patients with allergic diseases and the study of allergic disease mechanisms depend on a wide variety of assays that in various ways assess the presence and function of IgE antibody. The study of allergic diseases could benefit from the study of its 2 principle cellular participants, mast cells and basophils, but the basophil is more accessible than mast cells for ex vivo studies. Its functionality is tested by using 2 predominant methodologies: the secretion of mediators of allergic inflammation and the expression of proteins on the plasma membrane after stimulation. Each approach has benefits. There are also many operational details to consider regardless of which general approach is taken, and proper interpretation of the methods requires a good understanding of the reagents used and the receptors expressed on basophils and a detailed understanding of the factors regulating aggregation of cell-surface IgE.


Stepwise Reversible Oxidation of N-Peralkyl-Substituted NHC-CAAC Derived Triazaalkenes: Isolation of Radical Cations and Dications.
Herein, the isolation and characterization of N-peralkyl-substituted NHC-CAAC derived triazaalkenes in three oxidation states, neutral, radical cation, and dication, are reported. Cyclic voltammetry has shown the reversible electronic coupling between the first and second oxidation to be ΔE1/2 = 0.50 V. As a proof-of-principle, to demonstrate the electron-rich nature of the triazaalkene, it was shown that it can be used as an electron donor in the reduction of an aryldiazonium salt to the corresponding arene.


Exploring urinary extracellular vesicles for organ transplant monitoring: A comprehensive study for detection of allograft dysfunction using immune-specific markers.
Allograft dysfunction (AGD) is a common complication following solid organ transplantation (SOT). This study leverages the potential of urinary extracellular vesicles (UEVs) for the non-invasive detection of AGD. We aimed to assess the diagnostic value of T-cell and B-cell markers characteristic of T-cell-mediated and antibody-mediated rejection in UEV-mRNA using renal transplantation as a model. UEVs were isolated from 123 participants, spanning healthy controls, functional transplant recipients, and biopsy-proven AGD patients. T-cell and B-cell marker mRNA expressions were evaluated using RT-qPCR. We observed significant differences in marker expression between healthy controls and AGD patients. ROC analysis revealed an AUC of 0.80 for T-cell markers, 0.98 for B-cell markers, and 0.94 for combined markers. T-cell markers achieved 81.3 % sensitivity, 80 % specificity, and 80.4 % efficiency. A triad of T-cell markers (PRF1, OX40, and CD3e) increased sensitivity to 87.5 % and efficiency to 82.1 %. B-cell markers (CD20, CXCL3, CD46, and CF3) delivered 100 % sensitivity and 97.5 % specificity. The combined gene signature of T-cell and B-cell markers offered 93.8 % sensitivity and 95 % specificity. Our findings underscore the diagnostic potential of UEV-derived mRNA markers for T-cells and B-cells in AGD, suggesting a promising non-invasive strategy for monitoring graft health.


R loops: new modulators of genome dynamics and function.
R loops are nucleic acid structures composed of an RNA-DNA hybrid and a displaced single-stranded DNA. Recently, evidence has emerged that R loops occur more often in the genome and have greater physiological relevance, including roles in transcription and chromatin structure, than was previously predicted. Importantly, however, R loops are also a major threat to genome stability. For this reason, several DNA and RNA metabolism factors prevent R-loop formation in cells. Dysfunction of these factors causes R-loop accumulation, which leads to replication stress, genome instability, chromatin alterations or gene silencing, phenomena that are frequently associated with cancer and a number of genetic diseases. We review the current knowledge of the mechanisms controlling R loops and their putative relationship with disease.


Residential treatment of adolescents with severe behavioural problems.
The development of adolescents with severe behavioural problems receiving residential treatment in Holland was empirically studied during 1 year. Treatment methods included a standard program comprising behavioural modification and three specific treatment programs: psychodynamic treatment, structured community living and adventurous learning. The development of the youngsters who remained in the programs (N=78) was compared with the development of the youngsters who prematurely dropped out (N=20). All programs had positive developmental outcomes, adventurous learning and structured community living yielded the most behavioural improvement and the standard program the least, and psychodynamic treatment lay in between. Despite the positive developmental outcomes, for many of the youngsters prolongation of the treatment was still needed after 1 year. Requirements for outcome research in residential care are discussed.


In-depth analysis of potential PaAP2/ERF transcription factor related to fatty acid accumulation in avocado (Persea americana Mill.) and functional characterization of two PaAP2/ERF genes in transgenic tomato.
Fatty acids in avocado fruit are crucial components influencing taste as well as fruit quality and nutritional value. Changes to fatty acid contents and concentrations in avocado fruit are important because of the associated effects on sensory properties. Hence, plant physiologists and molecular biologists interested in elucidating the influence of transcription factors on fatty acid accumulation in avocado fruit. In this study, APETALA2/ethylene-responsive factor (AP2/ERF) family members in avocado (Persea americana Mill.) were systematically and comprehensively analyze to identify potential PaAP2/ERF genes related to fatty acid accumulation. The results of bioinformatics analysis and the expression profiles of the AP2/ERF members suggested that 10 highly expressed PaAP2/ERF genes may encode transcription factors with functions related to the fatty acid accumulation in the avocado mesocarp. Furthermore, PaWRI1 and PaWRI2, two AP2/ERF transcription factor genes in avocado, were functionally characterized regarding their effects on fatty acid accumulation. The transcriptome and biochemical analyses of PaWRI1-2-overexpressing transgenic tomato plants revealed the up-regulated expression of 17 unigenes related to fatty acid synthesis and triacylglycerol assembly as well as increased fatty acid contents relative to the corresponding levels in the wild-type plants. In contrast, the overexpression of PaWRI2 in transgenic tomato plants up-regulated the expression of only six unigenes associated with fatty acid synthesis and triacylglycerol assembly and negligibly affected fatty acid accumulation when compared with wild-type plants. This systematic analysis provides a foundation for future studies regarding AP2/ERF functions associated with fatty acid accumulation.


The comparison of percutaneous kyphoplasty and vertebroplasty for the management of stage III Kummell disease without neurological symptoms.
To compare the clinical and radiological outcomes of percutaneous kyphoplasty (PKP) and percutaneous vertebroplasty (PVP) in the treatment of stage III Kummell disease without neurological deficit. This retrospective study involved 41 patients with stage III Kummell disease without neurological deficit who underwent PKP or PVP from January 2018 to December 2019. Demographic data and clinical characteristics were comparable between these two groups before surgery. Operation time, volume of injected bone cement, intraoperative blood loss and time of hospital stay were analyzed. Visual analog scale (VAS) scoring and Oswestry disability index (ODI) scoring were assessed for each patient before and after operation. Radiographic follow-up was assessed by the height of anterior (Ha), the height of middle (Hm), Cobb's angle, and Vertebral wedge ratio (VWR). The preoperative and postoperative recovery values of these data were used for comparison. The two groups showed no significant difference in demographic features (p > 0.05). What's more, the operation time, intraoperative blood loss, and time of hospital stay revealed no sharp statistical distinctions either (p > 0.05), except PKP used more bone cement than PVP (7.4 ± 1.7 mL vs 4.7 ± 1.4 mL, p < 0.05). Radiographic data, such as the Ha improvement ratio (35.1 ± 10.2% vs 16.2 ± 9.4%), the Hm improvement ratio (41.8 ± 11.3% vs 22.4 ± 9.0%), the Cobb's angle improvement (10.0 ± 4.3° vs 3.5 ± 2.1°) and the VWR improvement ratio (30.0 ± 10.6% vs 12.7 ± 12.0%), were all better in PKP group than that in PVP group (p < 0.05). There were no statistical differences in the improvement of VAS and ODI 1-day after the surgery between these two groups (p > 0.05). However, at the final follow-up, VAS and ODI in PKP group were better than that in PVP (p < 0.05). Cement leakage, one of the most common complications, was less common in the PKP group than that in the PVP group (14.3% vs 45.0%, p < 0.05). And there was 1 case of adjacent vertebral fractures in both PKP and PVP (4.8% vs 5.0%, p > 0.05), which showed no statistical difference, and there were no severe complications recorded. For stage III Kummell disease, both PKP and PVP can relieve pain effectively. Moreover, PKP can obtain more satisfactory reduction effects and less cement leakage than PVP. We suggested that PKP was more suitable for stage III Kummell disease without neurological deficit compared to PVP from a vertebral reduction point of view.


Co5In(BTC)4[B2O4(OH)]2: the first MOF material constructed by borate polyanions and carboxylate mixed ligands.
A novel heterometallic organic-inorganic hybrid MOF material, Co5In(BTC)4[B2O4(OH)]2, has been synthesized under ionothermal conditions. Its structure is characterized as a 3D open framework constructed by the Co2.5In0.5[B2O4(OH)] cluster and the 1,3,5-benzenetricarboxylate ligand. Furthermore, its fluorescent and adsorption properties have also been studied.


Cross-tolerance between ethanol and levorphanol with respect to stimulation of plasma corticosterone.
Male rats chronically intoxicated with ethanol for at least two days were tolerant to the ethanol-induced stimulation of hypothalamic-pituitary-adrenal axis. Chronically intoxicated rats also were tolerant to stimulation of this axis by levorphanol but not by amphetamine or ether. In a similar manner, animals treated with levorphanol for two days were tolerant to stimulation of the hypothalamic-pituitary-adrenal axis by either levorphanol or ethanol. These observations provide further support for the hypothesis that endogenous opioids may be involved in the development of tolerance to ethanol.


Molecular characterization of hepcidin gene from mud loach (Misgurnus mizolepis; Cypriniformes).
The gene encoding hepcidin, an antimicrobial peptide, was isolated and characterized in the mud loach Misgurnus mizolepis (Cypriniformes). Mud loach hepcidin shows a considerable degree of structural homology to other vertebrate hamp1 orthologues at both the gene and protein levels, particularly with respect to its tripartite genomic organization, typical transcription-factor-binding motifs in its promoter, and conserved cysteine residues in the mature cationic peptide. The mud loach possesses at least two allelic forms of hamp1, which are expected to be translated into the same hepcidin preproprotein. The two alleles are transmitted from parental fish to offspring with a Mendelian inheritance pattern, as demonstrated with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) genotyping. Southern blot hybridization analysis showed a high degree of polymorphisms in the restriction patterns of individuals. Mud loach hamp1 mRNA is predominantly expressed in the liver, although many other tissues showed detectable levels of hamp1 transcripts in RT-PCR assay. Lipopolysaccharide and bacterial challenges induced significant hamp1 expression, whereas hamp1 was not clearly stimulated by polyinosinic:polycytidylic acid [poly(I:C)] injection. Iron overload and Cu exposure also elevated hamp1 transcripts in various tissues. The transcriptional activation of mud loach hamp1 in response to these stimuli varied among tissue types, and the liver appears predominantly involved in hepcidin-mediated iron regulation. However, hepcidin expression in the kidney and spleen was preferentially modulated by inflammation-mediated signals produced by immune challenges. Our results suggest that mud loach hepcidin has two basic functions, in iron regulation and antimicrobial activity, and that its transcription is also modulated by other environmental perturbations, including heavy metal exposure.


[Immunochemical properties of erythrocyte-specific histone H5 in salmonid fishes].
Comparative studies have been made on the immunochemical properties of histone H5 in Salmonidae species. High degree of homology between these histones and H5 histone from Oncorhynchus tschawytscha was demonstrated by microcomplement fixation. Properties of H5 histones in fish and birds are discussed.


CF healthcare workers feel unprepared in providing suitable end of life care and desire more education: Results of a nationwide survey.
Little is known about the depth of knowledge and preparedness of CF caregivers in delivering end of life and palliative care to CF patients and families. Nationwide survey questionnaires for CF care providers using the CF Foundation Listserv electronic web-based tool. The majority of non-physician CF care providers (55%) had more than 15 years of experience in their discipline and 84% of physician had greater than 15 years of experience. The majority reported that they felt "somewhat" or "very" involved in palliative or end of life care in their current role. Yet, when asked whether they felt adequately prepared to deliver palliative and end of life care, only 18% reported that they were "fully prepared" and 45% felt that they were only "minimally" or "not" prepared. Further, only one third of respondents received more than 10h of education in general palliative or end-of-life care, while only 10% had received more than 10h of education specific to CF end of life care. The majority (73%) of CF healthcare providers preferred more education specific to CF end of life care. CF healthcare providers are involved in CF end of life issues but a fair number did not understand their role and felt inadequately prepared in delivering suitable end of life and palliative care. Many desired more education in the provision of such care.


Squatter settlement and informal urbanization: causes and consequences.
Squatter settlement and informal urbanization trends in Addis Ababa were a great concern with highest population living in informal settlements. Squatter settlements were illegally built due to urbanization in an open space, farmland, steep slope, and along river buffer which do not have legal title deed particularly at expansion of cities. Formal land value in the city through time has been increasing. This study focused on the causes and consequences of squatter settlement and informal urbanization. In this study, household income, family size, occupation, and the characteristics of the squatter settlements regarding its physical, social, and economic dimensions were studied using physical observation, questionnaires, interviews, and focus group discussion. Systematic sampling technique was employed for questionnaires to investigate the actual causes and consequences. Among 10 districts in Wereda 03, districts 4, 7, 8, and 9 were purposely selected since there were recorded large numbers (964 households) of new squatter and informal settlements by Wereda 03 administration in one year (2018). Out of 964 newly settled squatter households, 49%, 31%, 11%, and 5% were site-related pulling factors, sloppy topography, migration, and urban policy, respectively. Major causes were migration of persons from rural to urban areas, too expensive formal land price, availability of sloppy land, condominium housing shortage, and could not afford 10/90 government-led condominium housing payment. In addition to this, land speculation and establishment of religious institutions have attracted informal settlement. Consequently, unplanned housing construction and squatter settlement in Addis Ababa has required high cost of infrastructure and unintegrated land use plan, and also it has been difficult to provide infrastructure in this settlement. The affordable housing policy was based on pro-poor development assisting the low-income group in minimum of 10/90 housing scheme, but the policy still did not answer the demand of low income rather than the high-income groups because the poor under poverty line are marginalized due to lack of income source to down payment. Hence, investing more on affordable housing targeting the urban poor to minimize informal settlement as home is the human right to live.


Development and validation with clinical samples of internally controlled multiplex real-time PCR for diagnosis of BKV and JCV infection in associated pathologies.
This article describes the development and validation with clinical samples of an internally controlled multiplex quantitative real-time PCR (QRT-PCR) for human polyomaviruses BK (BKV) and JC (JCV). Blood and urine samples from renal transplant recipients with suspected nephropathy, and cerebrospinal fluid (CSF) specimens from AIDS, natalizumab-treated and HIV-negative patients with suspected progressive multifocal leukoencephalopathy, previously checked for BKV and JCV by conventional PCR, were tested by QRT-PCR. All samples positive by conventional PCR were confirmed by QRT-PCR. Four cases of JCV-associated neurological infection, including all those detected in natalizumab-treated patients, and one case of BKV-related neurological infection were only identified by QRT-PCR. BKV was quantified in the CSF of neurological patients for the first time. Analyses of the Quality Control for Molecular Diagnostics 2010 panel were "highly satisfactory" for BKV and "satisfactory" for JCV. The QRT-PCR is specific and reproducible. It improves the sensitivity of conventional PCR for the diagnosis of BKV and JCV infection in various diseases.


Opportunities for translation: targeting DNA repair pathways in pancreatic cancer.
Pancreatic ductal adenocarcinoma (PDAC) remains one of the poorest prognosis neoplasms. It is typified by high levels of genomic aberrations and copy-number variation, intra-tumoural heterogeneity and resistance to conventional chemotherapy. Improved therapeutic options, ideally targeted against cancer-specific biological mechanisms, are urgently needed. Although induction of DNA damage and/or modulation of DNA damage response pathways are associated with the activity of a number of conventional PDAC chemotherapies, the effectiveness of this approach in the treatment of PDAC has not been comprehensively reviewed. Here, we review chemotherapeutic agents that have shown anti-cancer activity in PDAC and whose mechanisms of action involve modulation of DNA repair pathways. In addition, we highlight novel potential targets within these pathways based on the emerging understanding of PDAC biology and their exploitation as targets in other cancers.


A Dedicated Professional: Medicine Says Goodbye to Former TMA President Hugh Lamensdorf, MD.
Like all physicians, former Texas Medical Association President Hugh Lamensdorf, MD, made notes when he saw his patients. But the Fort Worth urologist, who passed away at age 82 in October, took this standard practice a bit further.


[Informativeness of different methods of visual stimulation in optochiasmatic arachnoiditis].
A comparative assessment of the informative value of visual evoked potentials (VEPs) has demonstrated that registration of VEPs in response to a diffuse flash of light makes it possible to objectively evaluate the status of the visual analyzer and to trace the course of the development and regression of the pathological process. In a long-term period of the recovery of the visual function in order to elucidate fine mechanisms of visual perception and to achieve objective optical correction of visual acuity, it is advisable to use VEPs in response to a structural stimulus.


Computational studies on thermo-kinetics aspects of pyrolysis of isopropyl acetate and its methyl, bromide and hydroxyl derivatives.
The gas-phase decomposition kinetics of isopropyl acetate (IPA) and its methyl, bromide and hydroxyl derivatives into the corresponding acid and propene were investigated using density functional theory (DFT) with the ωB97XD and M06-2x functionals, as well as the benchmark CBS-QB3 composite method. Transition state theory (TST) and RRKM theory calculations of rate constants under atmospheric pressure and in the fall-off regime were used to supplement the measured energy profiles. The results show that the formation of propene and bromoacetic acid is the most dominant pathway at the CBS-QB3 composite method, both kinetically and thermodynamically. There was a good agreement with experimental results. Pressures greater than 0.01 bar, corresponding to larger barrier heights are insufficient to ensure saturation of the measured rate coefficient when compared to the RRKM kinetic rates. Natural bond orbitals (NBO) charges, bond orders, bond indices, and synchronicity parameters all point to the considered pathways taking place via a homogenous, first-order concerted, as well as an asynchronous mechanism involving a non-planar cyclic six-membered transition state. The calculated data exhibit that the elongation of the Cα-O bond length and subsequent polarization of the Cα +δ…O-δ bond is the rate-determining step of the considered reactions in the cyclic transition state, which appears to be involved in this type of reaction.


Differential Impact of Anxious Misery Psychopathology on Multiple Representations of the Functional Connectome.
One aim of characterizing dimensional psychopathology is associating different domains of affective dysfunction with brain circuitry. The functional connectome, as measured by functional magnetic resonance imaging, can be modeled and associated with psychopathology through multiple methods; some methods assess univariate relationships while others summarize broad patterns of activity. It remains unclear whether different dimensions of psychopathology require different representations of the connectome to generate reproducible associations. Patients experiencing anxious misery symptomology (depression, anxiety, and trauma; n = 192) received resting-state functional magnetic resonance imaging scans. Three modeling approaches (seed-based correlation analysis, edgewise regression, and brain basis set modeling), each relying on increasingly broader representations of the functional connectome, were used to associate connectivity patterns with six data-driven dimensions of psychopathology: anxiety sensitivity, anxious arousal, rumination, anhedonia, insomnia, and negative affect. To protect against overfitting, 50 participants were held out in a testing dataset, leaving 142 participants as training data. Different modeling approaches varied in the extent to which they could model different symptom dimensions: seed-based correlation analysis failed to reproducibly model any symptoms, subsets of the connectome (edgewise regression) were sufficient to model insomnia and anxious arousal, and broad representations of the entire connectome (brain basis set modeling) were necessary to model negative affect and ruminative thought. These results indicate that different methods of representing the functional connectome differ in the degree that they can model different symptom dimensions, highlighting the potential sufficiency of subsets of connections for some dimensions and the necessity of connectome-wide approaches in others.


Clinical outcome of maintenance electroconvulsive therapy in comorbid Posttraumatic Stress Disorder and major depressive disorder.
Post-traumatic stress disorder (PTSD) and major depressive disorder (MDD) are prevalent and frequently comorbid. Approximately 42-48% of patients with PTSD also meet diagnostic criteria for MDD. Maintenance electroconvulsive therapy (mECT) has been found to be efficacious for the prevention of recurrence of MDD. This study investigated the efficacy of mECT in the treatment of MDD with and without comorbid syndromal PTSD. This retrospective study includes 36 patients, 26 with MDD and 10 with comorbid MDD & PTSD receiving monthly mECT for a mean of 1.5 years. The mean age was 52 ± 14 years and 25% were female. The change in PTSD and MDD symptoms in response to mECT was assessed using Clinical Global Impression - Severity Scale (CGI-S). Heart rate variability (HRV), 12-month hospitalization rate, suicide rate and all-cause mortality in response to mECT were assessed and compared between groups using repeated generalized linear regression (GLM) analysis. At mECT baseline, there were no statistically significant differences in CGI-S scores, HRV between patients with MDD alone and those with comorbid MDD and PTSD (P > 0.05). After 12-months of mECT, a significant increase in HRV (mean difference: 10.9 95%CI 4.8-20.3, p = 0.001) and decrease in CGI-S overall (mean difference: 3.5, 95% CI 3.3-3.6, p = 0.001)], PTSD (mean difference: 3.4, 95% CI 3.2-3.6, p = 0.001)], and MDD (mean difference: 3.8, 95% CI 3.5-3.9, p = 0.001)] symptoms in both groups were noted (p < 0.05). No psychiatric hospitalization or suicide occurred in any of the patients. Maintenance ECT is associated with improved HRV, reduction of both major depression and PTSD symptoms, and a favorable clinical outcome.


Next-generation proteomics faces new challenges in environmental biotechnology.
Environmental biotechnology relies on the exploration of novel biological systems and a thorough understanding of the underlying molecular mechanisms. Next-generation proteomics based on the latest generation of mass analyzers currently allows the recording of complete proteomes from any microorganism. Interpreting these data can be straightforward if the genome of the organism is established, or relatively easy to perform through proteogenomics approaches if a draft sequence can be obtained. However, next-generation proteomics faces new, interesting challenges when the organism is distantly related to previously characterized organisms or when mixtures of organisms have to be analyzed. New mass spectrometers and innovative bioinformatics tools are reshaping the possibilities of homology-based proteomics, proteogenomics, and metaproteomics for the characterization of biological systems. Novel time- and cost-effective screening strategies are also possible with this methodology, as exemplified by whole proteome thermal profiling and subpopulation proteomics. The complexity of environmental samples allows for unique developments of approaches and concepts.


Centration axis in refractive surgery.
The human eye is an asymmetric optical system and the real cornea is not a rotationally symmetrical volume. Each optical element in the eye has its own optical and neural axes. Defining the optimum center for laser ablation is difficult with many available approaches. We explain the various centration approaches (based on these reference axes) in refractive surgery and review their clinical outcomes. The line-of-sight (LOS) (the line joining the entrance pupil center with the fixation point) is often the recommended reference axis for representing wavefront aberrations of the whole eye (derived from the definition of chief ray in geometrical optics); however pupil centration can be unstable and change with the pupil size. The corneal vertex (CV) represents a stable preferable morphologic reference which is the best approximate for alignment to the visual axis. However, the corneal light reflex can be considered as non-constant, but dependent on the direction of gaze of the eye with respect to the light source. A compromise between the pupil and CV centered ablations is seen in the form of an asymmetric offset where the manifest refraction is referenced to the CV while the higher order aberrations are referenced to the pupil center. There is a need for a flexible choice of centration in excimer laser systems to design customized and non-customized treatments optimally.


Artificial intelligence: machine learning for chemical sciences.
Research in molecular sciences witnessed the rise and fall of Artificial Intelligence (AI)/ Machine Learning (ML) methods, especially artificial neural networks, few decades ago. However, we see a major resurgence in the use of modern ML methods in scientific research during the last few years. These methods have had phenomenal success in the areas of computer vision, speech recognition, natural language processing (NLP), etc. This has inspired chemists and biologists to apply these algorithms to problems in natural sciences. Availability of high performance Graphics Processing Unit (GPU) accelerators, large datasets, new algorithms, and libraries has enabled this surge. ML algorithms have successfully been applied to various domains in molecular sciences by providing much faster and sometimes more accurate solutions compared to traditional methods like Quantum Mechanical (QM) calculations, Density Functional Theory (DFT) or Molecular Mechanics (MM) based methods, etc. Some of the areas where the potential of ML methods are shown to be effective are in drug design, prediction of high-level quantum mechanical energies, molecular design, molecular dynamics materials, and retrosynthesis of organic compounds, etc. This article intends to conceptually introduce various modern ML methods and their relevance and applications in computational natural sciences. Synopsis Recent surge in the application of machine learning (ML) methods in fundamental sciences has led to a perspective that these methods may become important tools in chemical science. This perspective provides an overview of the modern ML methods and their successful applications in chemistry during the last few years.


How to treat isolated distal deep vein thrombosis.
Isolated distal deep vein thrombosis (IDDVT) is a frequent manifestation of venous thromboembolism (VTE), accounting for up to 50% cases of lower‑extremity deep vein thrombosis (DVT). As compared with proximal DVT, IDDVT is more frequently associated with transient risk factors and less often occurs unprovoked or in the presence of permanent risk factors. IDDVT generally carries a significantly lower risk of proximal extension, post‑thrombotic syndrome, and recurrence than proximal DVT. Nevertheless, some patient subgroups, such as those with active cancer, other predisposing permanent risk factors, prior VTE, unprovoked IDDVT, persistently restricted mobility, and trifurcation or bilateral involvement, exhibit a non‑negligible recurrence risk. Unlike in proximal DVT, the optimal therapeutic management of IDDVT remains uncertain. In clinical practice, the vast majority of IDDVT patients are managed with anticoagulation rather than with surveillance serial compression ultrasonography, which tends to be reserved to individuals at a high bleeding risk. Available data seem to favor anticoagulant therapy over no anticoagulation, thanks to a significant reduction in the risk for proximal extension and recurrence, without increased bleeding risk. Recent results of the RIDTS (Rivaroxaban for the Treatment of Symptomatic Isolated Distal Deep Vein Thrombosis) randomized clinical trial with rivaroxaban further support the use of anticoagulant therapy for 3 months over shorter durations (eg, ≤6 weeks). In this review, we offer an updated overview of the epidemiology, risk factors, and clinical course of IDDVT, with a focus on the therapeutic management in light of current guideline recommendations and most recent evidence. We also present real‑life clinical cases of IDDVT with proposed therapeutic approaches, and highlight major challenges and gaps in this field.


Evaluation of the accuracy of articular cartilage thickness measurement by B-mode ultrasonography with conventional imaging and real-time spatial compound ultrasonography imaging.
The present study aimed to quantify the thickness of articular cartilage (Tc) in vitro using both conventional and real-time spatial compound B-mode ultrasonography (US) with a clinically used transducer and to evaluate the accuracy of measurement by comparing the results with values obtained microscopically. Femoral condyle samples were obtained from a 6-month-old pig and a 3-year-old pig. B-mode US images with conventional imaging and real-time spatial compound imaging (RTSCI) of osteochondral blocks were acquired. Tc determined using US (Tc-US) was measured from line data parallel to US beam direction acquired from B-mode images with an objective method for determining cartilage surface and bone-cartilage interfaces at the peak brightness values. Tc was also determined under microscopy (Tc-optical) using the corresponding points from US measurement. Tc-US was compared with Tc-optical to assess accuracy. Tc-US correlated significantly with Tc in both conventional imaging and RTSCI (r = 0.961, 0.976, respectively). Bland-Altman plots showed mean differences between Tc-optical and Tc-US were -0.0073 mm and 0.0139 mm with standard deviations of 0.171 mm and 0.131 mm for conventional imaging and RTSCI, respectively. Our results show that Tc-US measurement using B-mode US allows accurate measurement of Tc. Considering correlation coefficients between Tc-US and Tc-optical, RTSCI US may offer higher accuracy for measuring Tc than conventional methods when an objective tissue border determination algorithm is used, even though both showed good accuracy in our study.


Delivering the promise of the Decade of Vaccines: opportunities and challenges in the development of high quality new vaccines.
The Decade of Vaccines (DoV) initiative, launched in 2010, has as its mission "to extend, by 2020 and beyond, the full benefits of immunization to all people, regardless of where they are born, who they are, or where they live". Through their life-saving vaccines, the research-based vaccine companies represented by the International Federation of Pharmaceutical Manufacturers & Associations (IFPMA) and the Biotechnology Industry Organization (BIO) make a major contribution toward this vision. In this article, we begin by summarizing progress made over the past three decades in research and development (R&D) of new and future vaccines, and identify the opportunities and challenges faced by the research-based vaccine industry. We then review the Global Vaccine Action Plan (GVAP) and provide IFPMA and BIO consensus perspectives on its six strategic objectives. Finally, we identify policy measures to support R&D of, and access to, high-quality, innovative vaccines.


Development of a scale to assess children's trust in general nurses.
Develop a Children's Trust in General Nurses Scale (CTGNS). In a cross-sectional investigation, 128 U.K. children (68 females and 60 males; mean age = 10 years and 4 months) completed the CTGNS and reported their trust in, and fear of, nurses. A total of 46 parents reported those dispositions and the frequency of their children visiting medical centres. The CTGNS showed acceptable internal consistency and factor structure. It was correlated with reported children's trust in nurses and visiting medical centres. The CTGNS will permit the investigation of children's trust in nurses and interventions to promote it.


Effect of d,l-propranolol on renal sympathetic baroreflex properties and aortic baroreceptor activity.
Sigmoid renal baroreflex curves relating mean arterial pressure to integrated renal sympathetic nerve activity were obtained in anaesthetized rabbits with previously implanted balloons to raise and lower blood pressure. Propranolol was infused to reach plasma levels averaging 324 ng/ml. This reduced blood pressure by 9.6 +/- 1.1 mm Hg, but had no effect on resting sympathetic discharge. Propranolol lowered the threshold of the renal baroreflex. Median blood pressure was reduced by 15.4 +/- 1.9 mmHg but there was no change in gain or sympathetic activity range. Thus, at a given blood pressure there was diminution of sympathetic discharge compared with control. Similar changes occurred after giving clonidine. However, "non-specific" produced by bleeding or nitroprusside infusion produced no resetting of the baroreflex curves, though the resting sympathetic discharge increased. The effects of propranolol (plasma levels 137 and 348 ng/ml) on arterial baroreceptor discharge were studied by deriving mean arterial pressure-integrated aortic nerve activity curves. Propranolol produced a reduction of aortic nerve discharge of about 7% of control. Single unit analysis showed a small reduction in firing frequency/sec near threshold, which was sufficient to explain the changes in integrated aortic nerve discharge. Since the changes in input from the aortic baroreceptors do not account for the reduction in threshold of the renal baroreflex, we conclude that the latter is due to the central nervous action of propranolol.


Prevalence of multidrug-, extensive drug-, and pandrug-resistant commensal Escherichia coli isolated from healthy humans in community settings in low- and middle-income countries: a systematic review and meta-analysis.
The majority of existing studies aimed at investigating the incidence and prevalence of multidrug-resistance by bacteria have been performed in healthcare settings. Relatively few studies have been conducted in community settings, but these have consistently shown a high prevalence of multidrug-resistant bacteria in low- and middle-income countries (LMICs). To provide an appraisal of the evidence on the high prevalence of multidrug-, extensive drug-, and pandrug-resistance in commensal Escherichia coli isolates from human sources in community settings in LMICs. Using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, PubMed, EMBASE, MEDLINE, Web of Science, CINAHL, and Cochrane Library databases were systematically searched with the search string: 'Enterobacteriaceae', OR 'E. coli', OR 'Escherichia coli', AND 'antibiotic resistance', OR 'antimicrobial resistance', OR 'drug-resistance', AND 'prevalence', OR 'incidence', OR 'morbidity', OR 'odds ratio', OR 'risk ratio', OR 'confidence interval', OR 'p-value', OR 'rate'. Data were extracted and proportional meta-analysis was performed using the Freeman-Tukey transformation random effect model. The prevalence of multidrug-, extensive drug- and pandrug-resistance were extracted from articles that met our inclusion criteria and pooled together after a systematic screening of 9,369 items. The prevalence of multidrug-resistance was 28% of 14,336 total cases of isolates tested, 95% CI: 23-32. Extensive drug-resistance was 24% of 8,686 total cases of isolates tested, 95% CI: 14-36. Lastly, pandrug-resistance was 5% of 5,670 total cases of isolates tested, 95% CI: 3-8. This paper provides an appraisal of the evidence on the high prevalence of multidrug-, extensive drug- and pandrug-resistance by commensal E. coli in community settings in LMICs. Our results call for greater effort to be placed at the community level in the design of new and improved public health policies to counter the global threat of antibiotic-resistant infections and bacteria.


SPARC promoter hypermethylation in colorectal cancers can be reversed by 5-Aza-2'deoxycytidine to increase SPARC expression and improve therapy response.
Poor clinical outcomes in cancer can often be attributed to inadequate response to chemotherapy. Strategies to overcome either primary or acquired chemoresistance may ultimately impact on patients' survival favourably. We previously showed that lower levels of SPARC were associated with therapy-refractory colorectal cancers (CRC), and that upregulating its expression enhances chemo-sensitivity resulting in greater tumour regression in vivo. Here, we examined aberrant hypermethylation of the SPARC promoter as a potential mechanism for repressing SPARC in CRCs and whether restoration of its expression with a demethylating agent 5-Aza-2'deoxycytidine (5-Aza) could enhance chemosensitivity. Initially, the methylation status of the SPARC promoter from primary human CRCs were assessed following isolation of genomic DNA from laser capture microdissected specimens by direct DNA sequencing. MIP101, RKO, HCT 116, and HT-29 CRC cell lines were also used to evaluate the effect of 5-Aza on: SPARC promoter methylation, SPARC expression, the interaction between DNMT1 and the SPARC promoter (ChIP assay), cell viability, apoptosis, and cell proliferation. Our results revealed global hypermethylation of the SPARC promoter in CRCs, and identified specific CpG sites that were consistently methylated in CRCs but not in normal colon. We also demonstrate that SPARC repression in CRC cell lines could be reversed following exposure to 5-Aza, which resulted in increased SPARC expression, leading to a significant reduction in cell viability (by an additional 39% in RKO cells) and greater apoptosis (an additional 18% in RKO cells), when combined with 5-FU in vitro (in comparison to 5-FU alone). Our exciting findings suggest potential diagnostic markers of CRCs based on specific methylated CpG sites. Moreover, the results reveal the therapeutic utility of employing demethylating agents to improve response through augmentation of SPARC expression.


Ecophysiological studies on the shrub Vaccinium myrtillus L. taken from a wide altitudinal range.
Observations have been made on the gas exchange and morphology of Vaccinium myrtillus taken from altitudes of 200 m, 610 m and 1,100 m along an altitudinal gradient in central Scotland. Under saturating irradiance, optimum temperatures and a range of vapour pressure deficits, photosynthetic rate and stomatal conductance increased with the altitude of origin of the populations. Correlated with these increases was an increase in the adaxial stomatal density with altitude. This response to altitude could be simulated in controlled conditions, by growing plants in a CO2 concentration below ambient, similar to that expected at altitude.Plant height decreased with altitude, a feature which was maintained in cultivation. Stem rigidity declined with altitude, in a manner which is predicted to limit the reproductive capacity of the population from 1,100 m in high wind speeds.Total leaf nitrogen increased with altitude. The nitrogen economy of the shoot is discussed in terms of nitrogen availability for stems and leaves and its control over maximum rates of photosynthesis, competitive ability and reproductive capacity.


Preparation and characterization of open-tubular capillary column modified with graphene oxide nanosheets for the separation of small organic molecules.
A novel coated capillary was prepared by immobilizing graphene oxide (GO) on the fused-silica capillary (75 μm i.d.) which was derivatized by 3-aminopropyl-trimethoxysilane (APTMS). The bare capillary, APTMS modified capillary (NH2-capillary) and GO coated capillary (GO-capillary) were characterized by streaming potentials (SPs), fluorescence microscope and scanning electron microscope (SEM). The results indicated that the capillary was successfully modified with GO sheets via covalent bonding and electrostatic effect. Compared with bare capillary, greater separation efficiency was achieved by GO-capillary column as a result of the increasing interactions between the small organic molecules and the inner wall of the GO-capillary column originated from the π-π electrostatic stacking. For three consecutive runs, the intra-day relative standard deviations (RSDs) of migration time and peak areas were 0.6-4.3% and 2.8-9.3%, respectively. The inter-day relative standard deviations of migration time and peak areas were 0.2-8.3% and 4.5-9.6%. Additionally, one GO-capillary column could be used for more than 100 runs with no observable changes on the separation efficiency.