CD27 co-stimulation increases the abundance of regulatory T cells and reduces atherosclerosis in hyperlipidaemic mice.
The co-stimulatory receptor CD27 modulates responses of T cells, B cells, and NK cells. Various T cell subsets participate in atherogenesis. However, the role of CD27 in atherosclerosis remains unexplored. Here we investigated the effect of bone marrow-derived and systemic CD27 deficiency in Apolipoprotein E-deficient (Apoe-/-) mice in early and advanced stages of atherosclerosis. Lethally-irradiated Apoe-/- mice reconstituted with Cd27-/-Apoe-/- bone marrow and consuming an atherogenic diet displayed a markedly increased plaque size and lesional inflammation compared to mice receiving Cd27+/+Apoe-/- bone marrow. Accordingly, chow diet-fed Cd27-/-Apoe-/- mice showed exacerbated lesion development and increased inflammation at the age of 18 weeks. At a more advanced stage of atherosclerosis (28 weeks), lesion size and phenotype did not differ between the two groups. Systemic and bone marrow-derived CD27 deficiency reduced the abundance of regulatory T cells (Treg) in blood, lymphoid organs, and the aorta. Numbers of other immune cells were not affected while expression of inflammatory cytokine genes (e.g. IL-1β and IL-6) was increased in the aorta when haematopoietic CD27 was lacking. In vitro, Tregs of CD27-deficient mice showed similar suppressive capacity compared with their wild-type controls and migrated equally towards CCL19 and CCL21. However, thymic Cd27-/- Tregs underwent increased apoptosis and expressed fewer markers of proliferation in vivo. Reconstitution of Cd27-/-Apoe-/- mice with Cd27+/+Apoe-/- Tregs reversed the increase in atherosclerosis. We demonstrate that CD27 co-stimulation increases the number of Tregs and limits lesion development and inflammation in experimental atherosclerosis, particularly during early stages of disease. Thus, our study suggests that promotion of CD27 function may mitigate atherosclerosis.


Experimental and computational phase boundary mapping of Co4Sn6Te6.
Binary Co4Sb12 skutterudite (also known as CoSb3) has been extensively studied; however, its mixed-anion counterparts remain largely unexplored in terms of their phase stability and thermoelectric properties. In the search for complex anionic analogs of the binary skutterudite, we begin by investigating the Co4Sb12-Co4Sn6Te6 pseudo-binary phase diagram. We observe no quaternary skutterudite phases and as such, focus our investigations on the ternary Co4Sn6Te6 via experimental phase boundary mapping, transport measurements, and first-principles calculations. Phase boundary mapping using traditional bulk syntheses reveals that the Co4Sn6Te6 exhibits electronic properties ranging from a degenerate p-type behavior to an intrinsic behavior. Under Sn-rich conditions, Hall measurements indicate degenerate p-type carrier concentrations and high hole mobility. The acceptor defect SnTe, and donor defects TeSn and Coi are the predominant defects and rationally correspond to regions of high Sn, Te, and Co, respectively. Consideration of the defect energetics indicates that p-type extrinsic doping is plausible; however, SnTe is likely a killer defect that limits n-type dopability. We find that the hole carrier concentration in Co4Sn6Te6 can be further optimized by extrinsic p-type doping under Sn-rich growth conditions.


Cohesin mutations are synthetic lethal with stimulation of WNT signaling.
Mutations in genes encoding subunits of the cohesin complex are common in several cancers, but may also expose druggable vulnerabilities. We generated isogenic MCF10A cell lines with deletion mutations of genes encoding cohesin subunits SMC3, RAD21, and STAG2 and screened for synthetic lethality with 3009 FDA-approved compounds. The screen identified several compounds that interfere with transcription, DNA damage repair and the cell cycle. Unexpectedly, one of the top 'hits' was a GSK3 inhibitor, an agonist of Wnt signaling. We show that sensitivity to GSK3 inhibition is likely due to stabilization of β-catenin in cohesin-mutant cells, and that Wnt-responsive gene expression is highly sensitized in STAG2-mutant CMK leukemia cells. Moreover, Wnt activity is enhanced in zebrafish mutant for cohesin subunits stag2b and rad21. Our results suggest that cohesin mutations could progress oncogenesis by enhancing Wnt signaling, and that targeting the Wnt pathway may represent a novel therapeutic strategy for cohesin-mutant cancers.


How to Interpret Resting-State fMRI: Ask Your Participants.
Resting-state fMRI (rsfMRI) reveals brain dynamics in a task-unconstrained environment as subjects let their minds wander freely. Consequently, resting subjects navigate a rich space of cognitive and perceptual states (i.e., ongoing experience). How this ongoing experience shapes rsfMRI summary metrics (e.g., functional connectivity) is unknown, yet likely to contribute uniquely to within- and between-subject differences. Here we argue that understanding the role of ongoing experience in rsfMRI requires access to standardized, temporally resolved, scientifically validated first-person descriptions of those experiences. We suggest best practices for obtaining those descriptions via introspective methods appropriately adapted for use in fMRI research. We conclude with a set of guidelines for fusing these two data types to answer pressing questions about the etiology of rsfMRI.


Publication rates of full-text journal articles converted from abstracts presented during the 22(nd) Turkish National Urology Congress.
To analyze the publication rates of full-text journal articles converted from the abstracts presented in the 22(nd) Turkish National Urology Congress in 2012. A total of 576 abstracts accepted for presentation at the 22(nd) Turkish National Urology Association Meeting were identified from the published abstract book. The abstracts were categorized into subsections such as endourology and pediatric urology. The subsequent publication rate for the studies was evaluated by scanning PubMed Medline. Abstracts published before the proceedings were excluded from the study. The abstracts were categorized as being presented orally (n=155), by poster (n=421), or by video (n=78). Of the 28 (18.3%) of 155 oral and 34 (8.15%) of 421 poster presentations, were subsequently published in several journals until March 2015. The publication rates of the abstracts based on urology subsections were as follows: neurology (25%), andrology (18.6%), endourology (17.2%), urolithiasis (15.3%), general urology (12.5%), infectious diseases (7.14%), pediatric urology (6.25%), uro-gynecology (6.06%), reconstructive urology (5.8%), and urooncology (3.8%). The average time to publication was 11.77 (0-33) months. This is the first study assessing the publication rates of abstracts presented at a Turkish National Urology Congress. It reveals that more qualified randomized studies need to be done to improve the rate of publication.


A differential autophagic response to hyperglycemia in the developing murine embryo.
Autophagy is critical to the process of development because mouse models have shown that lack of autophagy leads to developmental arrest during the pre-implantation stage of embryogenesis. The process of autophagy is regulated through signaling pathways, which respond to the cellular environment. Therefore, any alteration in the environment may lead to the dysregulation of the autophagic process potentially resulting in cell death. Using both in vitro and in vivo models to study autophagy in the pre-implantation murine embryo, we observed that the cells respond to environmental stressors (i.e. hyperglycemic environment) by increasing activation of autophagy in a differential pattern within the embryo. This upregulation is accompanied by an increase in apoptosis, which appears to plateau at high concentrations of glucose. The activation of the autophagic pathway was further confirmed by an increase in GAPDH activity in both in vivo and in vitro hyperglycemic models, which has been linked to autophagy through the activation of the Atg12 gene. Furthermore, this increase in autophagy in response to a hyperglycemic environment was observed as early as the oocyte stage. In conclusion, in this study, we provided evidence for a differential response of elevated activation of autophagy in embryos and oocytes exposed to a hyperglycemic environment.


Development of a new water-soluble fluorescence probe for hypochlorous acid detection in drinking water.
Responsive small-molecule fluorescence probe specific for target analyte detection is an emerging technology for food safety and quality analysis. In this work, we report a new water soluble small-molecule fluorescence probe (PG) for the detection of hypochlorous acid (HOCl) in drinking water samples. Probe PG was developed by coupling of a glucosamine into 10-methyl-10H-phenothiazine fluorophore with a HOCl-responsive C=N bond. The thioether is another recognition site that can be oxidized to be sulfoxide in water. Due to the specific reactions triggered by HOCl, probe PG's absorption band is blue shifted from 388 to 340 nm, and fluorescence at 488 nm is more than 55-fold enhanced. Probe PG features high fluorescence stability in PBS buffer with varied pH, fast response and high selectivity to HOCl. The application of the probe PG for HOCl detection in real-world samples is demonstrated by HOCl detection in drinking water, including tap water, purified water, and spring water samples. The recoveries of this method for HOCl detection in drinking water are in the range of 99.17-102.3%. This work thus provides a new method for HOCl detection in drinking water with high precision and accuracy.


Predictors of Definitive Airway Sans Hypoxia/Hypotension on First Attempt (DASH-1A) Success in Traumatically Injured Patients Undergoing Prehospital Intubation.
Background: Prehospital intubation success is routinely treated as a dichotomous outcome based on an endotracheal tube passing through vocal cords regardless of number of attempts or occurrence of hypoxia, or hypotension, which are associated with worse outcomes. We explore patient, provider, and procedure-related variables associated with successful definitive airway sans hypoxia/hypotension on first attempt (DASH-1A) in traumatically injured subjects undergoing endotracheal intubation at the scene of injury by a helicopter EMS system.Methods: This single-center retrospective chart review included patients with traumatic injuries and at least one attempted intubation by helicopter EMS at the scene of injury. Demographic and clinical variables were tested for association with DASH-1A and overall first-attempt success using univariate comparisons and multivariable logistic regression to produce adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Purposeful backwards stepwise elimination was used to develop logistic regression models for outcomes. Initial inclusion of covariates in multivariable models was based on clinical judgement, known or suspected risk factors and confounders for intubation success, and univariate associations.Results: Of 419 subjects screened, 263 met inclusion criteria. Median age was 34 years and the majority of subjects were Caucasian (95%), male (76%), and suffered blunt trauma (90%). The endotracheal tube was successfully placed on the first attempt in 198 (75.3%) of patients, but only 142 (55.3%) had a successful DASH-1A, and overall, 246 (94%) had an endotracheal tube passed successfully before hospital arrival. Factors significantly associated with successful DASH-1A were no ground EMS intubation attempt prior to arrival [aOR 2.2 (CI 1.0-4.9)], lack of airway secretions/blood [1.9 (1.0-3.4)], Cormack-Lehane Score of I and II [12.3 (4.5-33.2) & 3.2 (1.2-9.1), respectively], and bougie use [5.4 (1.8-15.8)]. For endotracheal tube passing only, the following were significantly associated with first pass success: grade of view I and II [aORs 87.3 (CI 25.8-295.7) & 6.8 (2.3-19.5), respectively], lack of secretions/blood [4.9 (2.1-11.2), bougie use [7.8 (2.3-26.3)], direct laryngoscopy [5.1 (1.5-17.0)] and not using apneic oxygenation through a nasal cannula [2.5 (1.1-5.6)].Conclusion: In our helicopter EMS system, successful endotracheal intubation on the first attempt and without an episode of hypoxia was associated with no ground EMS intubation attempt prior to flight crew arrival, lack of airway secretions/blood, Cormack-Lehane Score, and bougie use.


Decreased low-density lipoprotein receptor-related protein 1 expression in pro-inflammatory monocytes is associated with subclinical atherosclerosis.
Subclinical atherosclerosis (SCA) occurs in asymptomatic individuals. Blood peripheral monocytes are involved in the development of atherosclerosis. Circulating monocytes acquire pro-inflammatory profiles, and they are involved in the early stages of atherosclerosis development. Low-density lipoprotein Receptor-related Protein 1 (LRP1) is expressed in monocytes, mainly in classical and intermediate subsets. Although LRP1 is highly expressed in macrophages and vascular smooth muscle cells (VSMCs) in atherosclerotic plaque formation, its expression in circulating monocytes has not been studied in SCA. The aim of this study was to characterize the LRP1 expression level in circulating monocytes of individuals with SCA and compared with individuals with low (LR) and intermediate (IR) risk of cardiovascular diseases, both without evidence of atherosclerotic lesions in carotid and coronary arteries. LRP1 and additional markers (CD11b, CD11c, and CD36) at cell surface of monocytes were analyzed by flow cytometry assays, whereas LRP1 and pro-inflammatory factors gene expressions were measured in isolated monocytes by quantitative RT-PCRs. Both LRP1 protein and LRP1 mRNA were significantly reduced in monocytes in SCA and IR respect to LR. Conversely, CD36, CD11b, and CD11c monocytic markers showed no significant changes between the different study groups. Finally, increased gene expressions of TNF-α and IL-1β were detected in monocytes of SCA, which were associated with decreased LRP1 expression at the cell surface in total monocytes. In summary, we propose that the decreased LRP1 expression at cell surface in total monocytes with pro-inflammatory profile is associated with the development of atherosclerosis in asymptomatic individuals.


C-reactive protein and serum amyloid A protein in neonatal infections.
In this study, we examine C-reactive protein (CRP) and serum amyloid protein A (SAA). Although the former is the best known and most commonly used indicator of inflammation, certain considerations underline the inadequacy of CRP determination alone for the early diagnosis of infection. In fact symptoms often precede the CRP elevation. SAA protein comprises a family of polymorphic apolipoproteins produced mainly by the liver, and several studies have stressed its importance in the diagnosis and monitoring of various diseases. Pathological SAA values are often detected in association with normal CRP concentrations. SAA rises earlier and more sharply than CRP. Finally, contrary to CRP, SAA presents the same trend in viral as well as bacterial infections. Although the data available on SAA in neonates are currently very limited, it is possible to postulate a role of primary importance for SAA in the management of neonatal infections.


Endoscopic extradural anterior clinoidectomy and optic nerve decompression through a pterional port.
Since the first description of the intradural removal of the anterior clinoid process, numerous refinements and modifications have been proposed to simplify and enhance the safety of the technique. The growing use of endoscopes in endonasal and transcranial approaches has changed the traditional management of many skull base lesions. We describe an endoscopic extradural anterior clinoidectomy and optic nerve decompression through a minimally invasive pterional port. Minimally invasive optic nerve decompression, with endoscopic extradural anterior clinoidectomy, through a pterional keyhole craniotomy was performed on five preserved cadaveric heads. The endoscopic pterional port provided a shorter and more direct route to the anterior clinoid region, and helped avoid unnecessary and extensive bone removal. An extradural approach helped minimize complications associated with infraction of the subdural space and allowed for the maintenance of visibility while drilling with continuous irrigation. Adequate 270° bone decompression of the optic canal was achieved in all specimens. Endoscopic extradural anterior clinoidectomy and optic nerve decompression is feasible through a single minimally invasive pterional port.


Adjusted weight anticoagulation for radial approach in elective coronarography: the AWARE coronarography study.
To evaluate the feasibility and safety of an anticoagulation adapted regimen for transradial coronary angiography. We randomly assigned 162 consecutive patients who benefited from an elective transradial approach for coronarography to receive either a standard dose of 5,000 IU heparin or 50 IU/kg with an upper limit of 5,000 IU. Patients under anti-vitamin K therapy were excluded. The TRband compression system was employed for the entire population after the procedure. Radial artery patency, the primary endpoint, was evaluated with Doppler before discharge from the hospital. Secondary endpoints were: ACT level immediately before sheath removal, compression length and bleeding complications. Both groups were well matched. ACT level is significantly lower in the adjusted anticoagulation group (231.4 min, vs. 265.6 min, p<10-4). Radial compression time was higher in the standard protocol group (235.5 min, vs. 204.5 min, p<10-5). No radial occlusion was noted, whatever the group considered. Local haematoma is less frequent in the 50 IU/kg group, with no statistical difference. A weight-adjusted heparin dose allows for lower ACT levels and decreases in radial compression time without increase in radial artery occlusion. The impact on bleeding complication needs further evaluation in larger series.


[Quantitative PCR in the diagnosis of Leishmania].
Polymerase chain reaction (PCR) is a sensitive and rapid method for the diagnosis of canine Leishmania infection and can be performed on a variety of biological samples, including peripheral blood, lymph node, bone marrow and skin. Standard PCR requires electrophoretic analysis of the amplification products and is usually not suitable for quantification of the template DNA (unless competitor-based or other methods are developed), being of reduced usefulness when accurate monitoring of target DNA is required. Quantitative real-time PCR allows the continuous monitoring of the accumulation of PCR products during the amplification reaction. This allows the identification of the cycle of near-logarithmic PCR product generation (threshold cycle) and, by inference, the relative quantification of the template DNA present at the start of the reaction. Since the amplification product are monitored in "real-time" as they form cycle-by-cycle, no post-amplification handling is required. The absolute quantification is performed according either to an internal standard co-amplified with the sample DNA, or to an external standard curve obtained by parallel amplification of serial known concentrations of a reference DNA sequence. From the quantification of the template DNA, an estimation of the relative load of parasites in the different samples can be obtained. The advantages compared to standard and semi-quantitative PCR techniques are reduction of the assay's time and contamination risks, and improved sensitivity. As for standard PCR, the minimal components of the quantitative PCR reaction mixture are the DNA target of the amplification, an oligonucleotide primer pair flanking the target sequence, a suitable DNA polymerase, deoxynucleotides, buffer and salts. Different technologies have been set up for the monitoring of amplification products, generally based on the use of fluorescent probes. For instance, SYBR Green technology is a non-specific detection system based on a fluorescent dsDNA intercalator and it is applicable to all potential targets. TaqMan technology is more specific since performs the direct assessment of the amount of amplified DNA using a fluorescent probe specific for the target sequence flanked by the primer pair. This probe is an oligonucleotide labelled with a reporter dye (fluorescent) and a quencher (which absorbs the fluorescent signal generated by the reporter). The thermic protocol of amplification allows the binding of the fluorescent probe to the target sequence before the binding of the primers and the starting of the polymerization by Taq polymerase. During polymerization, 5'-3' exonuclease activity of Taq polymerase digests the probe and in this way the reporter dye is released from the probe and a fluorescent signal is detected. The intensity of the signal accumulates at the end of each cycle and is related to the amount of the amplification product. In recent years, quantitative PCR methods based either on SYBR Green or TaqMan technology have been set up for the quantification of Leishmania in mouse liver, mouse skin and human peripheral blood, targeting either single-copy chromosomal or multi-copy minicircle sequences with high sensitivity and reproducibility. In particular, real-time PCR seems to be a reliable, rapid and noninvasive method for the diagnosis and follow up of visceral leishmaniasis in humans. At present, the application of real-time PCR for research and clinical diagnosis of Leishmania infection in dogs is still foreseable. As for standard PCR, the high sensitivity of real-time PCR could allow the use of blood sampling that is less invasive and easily performed for monitoring the status of the dogs. The development of a real-time PCR assay for Leishmania infantum infection in dogs could support the standard and optimized serological and PCR methods currenly in use for the diagnosis and follow-up of canine leishmaniasis, and perhaps prediction of recurrences associated with tissue loads of residual pathogens after treatment. At this regard, a TaqMan Real Time PCR method developed for the quantification of Leishmania infantum minicircle DNA in peripheral blood of naturally infected dogs sampled before and at different time points after the beginning of a standard antileishmanial therapy will be illustrated.


Acute effect of carbamazepine on corticothalamic 5-9-Hz and thalamocortical spindle (10-16-Hz) oscillations in the rat.
A major side effect of carbamazepine (CBZ), a drug used to treat neurological and neuropsychiatric disorders, is drowsiness, a state characterized by increased slow-wave oscillations with the emergence of sleep spindles in the electroencephalogram (EEG). We conducted cortical EEG and thalamic cellular recordings in freely moving or lightly anesthetized rats to explore the impact of CBZ within the intact corticothalamic (CT)-thalamocortical (TC) network, more specifically on CT 5-9-Hz and TC spindle (10-16-Hz) oscillations. Two to three successive 5-9-Hz waves were followed by a spindle in the cortical EEG. A single systemic injection of CBZ (20 mg/kg) induced a significant increase in the power of EEG 5-9-Hz oscillations and spindles. Intracellular recordings of glutamatergic TC neurons revealed 5-9-Hz depolarizing wave-hyperpolarizing wave sequences prolonged by robust, rhythmic spindle-frequency hyperpolarizing waves. This hybrid sequence occurred during a slow hyperpolarizing trough, and was at least 10 times more frequent under the CBZ condition than under the control condition. The hyperpolarizing waves reversed at approximately -70 mV, and became depolarizing when recorded with KCl-filled intracellular micropipettes, indicating that they were GABAA receptor-mediated potentials. In neurons of the GABAergic thalamic reticular nucleus, the principal source of TC GABAergic inputs, CBZ augmented both the number and the duration of sequences of rhythmic spindle-frequency bursts of action potentials. This indicates that these GABAergic neurons are responsible for the generation of at least the spindle-frequency hyperpolarizing waves in TC neurons. In conclusion, CBZ potentiates GABAA receptor-mediated TC spindle oscillations. Furthermore, we propose that CT 5-9-Hz waves can trigger TC spindles.


Interactions of xylazine and acepromazine with oxytocin and the effects of these interactions on intrauterine pressure in normal mares and mares with delayed uterine clearance.
The effects of the sedatives xylazine (predominantly alpha2 agonist) and acepromazine (predominantly alpha1 antagonist) and their influence on intrauterine pressure were measured in four reproductively normal mares and four mares with delayed uterine clearance. Intrauterine pressure was measured in each mare during oestrus for three 100 min periods using an 8-F catheter with three discrete pressure sensors. After 10 min of baseline recording, xylazine, acepromazine or saline was administered i.v. Oxytocin was administered i.v. after a further 30 min, and pressure recordings were continued for 60 min. The pressure changes analysed were: number of uterine contractions; time of onset and duration of the first contraction; and the time at which intrauterine pressure changed from baseline. Data were analysed using the mixed procedure of the Statistical Analysis System. ANOVA detected an effect of treatment (P < 0.0001) and a treatment by group interaction (P < 0.001). Xylazine administration caused a tetanic contraction in all mares. When mares with delayed uterine clearance were sedated with xylazine before administration of oxytocin, the duration of increased intrauterine pressure was longer than that of normal mares (24.87 +/- 2.52 and 15.81 +/- 2.46, respectively; P < 0.0001). Acepromazine administration had no effect on the oxytocin-induced contraction pattern in normal mares, but there was a decrease in the number of contractions in mares with delayed uterine clearance. The enhanced response to alpha-agonists and -antagonists observed in mares with delayed uterine clearance when the drugs were administered before oxytocin may be due to denervation supersensitivity. After mating, sedation of mares with xylazine is preferred to sedation with acepromazine, as xylazine increases uterine contraction time.


Association of Osteoporosis with Anthropometric Measures in a Representative Sample of Iranian Adults: The Iranian Multicenter Osteoporosis Study.
Osteoporosis and obesity are two major public health problems worldwide. Considering the conflicting results about the association between anthropometric measurement and bone mineral density (BMD) and also differences between various races, this study was designed to examine the relationship between anthropometric measurements and BMD in a sample of Iranian adults. This cross-sectional population-based study was conducted on 2625 Iranian adults aged 18 and above who were selected using multistage, cluster sampling method from Sanandaj and Arak (two cities of Iran). The evaluated variables included age, sex, height, weight, body mass index (BMI), BMD, and waist and hip circumferences. The correlations between anthropometric measures and BMD in three bone areas (total hip, femoral neck, and spine) were observed in four sex/age groups (men <50 years, men ≥50 years, and pre- and postmenopausal women). Of all the 2625 participants in the Iranian Multicenter Osteoporosis Study, 2022 (1303 women and 719 men) entered into our survey and were stratified into four sex/age groups. According to the results, increasing BMI was directly associated with BMD increase, while an inverse association was observed between waist-to-hip ratio (WHR) and total hip BMD. In a similar analysis on the femoral neck and WHR, the correlation coefficients in premenopausal women and men ≥50 years were reported as being the highest and the lowest, respectively, among the four groups. Our results showed that high BMI is a protective factor (positive correlation), and high WHR is a risk factor for osteoporosis, although it should be reminded that we could not specifically define which factors including lean tissue mass, fat mass, and total weight are really affecting BMD increase in the overweight/obese participants.


COVID-19: repercussions of nursing, structuring and resolutivity of national health systems.
To analyze the repercussions of Nursing, the structuring and resolution of National Health Systems in facing the new coronavirus (SARS-CoV-2) in selected countries. Reflection article on the confrontation of COVID-19 by the National Health Systems of China, United States of America, Italy, United Kingdom, Portugal, Cuba and Brazil, from information disseminated in different media and in the literature. The response of health systems depended more on political decisions than on their structuring and organization. Nursing, being the front line, was the profession most affected in number of cases and deaths. The reflection shows that the countries' economic and political issues interfered in the response to COVID-19 and what the role played by Nursing is essential in the front line to face the pandemic.


The cyclin-dependent kinase inhibitor p21 is regulated by RNA-binding protein PCBP4 via mRNA stability.
RNA-binding proteins (RBPs) play a major role in many post-transcriptional processes, including mRNA stability, alternative splicing and translation. PCBP4, also called MCG10, is an RBP belonging to the poly(C)-binding protein family and a target of p53 tumor suppressor. Ectopic expression of PCBP4 induces cell-cycle arrest in G₂ and apoptosis. To identify RNA targets regulated by PCBP4 and further decipher its function, we generated multiple cell lines in which PCBP4 is either inducibly over-expressed or knocked down. We found that PCBP4 expression decreases cyclin-dependent kinase inhibitor p21 induction in response to DNA damage. We also provided evidence that PCBP4 regulates p21 expression independently of p53. In addition, we showed that a deficiency in PCBP4 enhances p21 induction upon DNA damage. To validate PCBP4 regulation of p21, we made PCBP4-deficient mice and showed that p21 expression is markedly increased in PCBP4-deficient primary mouse embryo fibroblasts compared to that in wild-type counterparts. Finally, we uncovered that PCBP4 binds to the 3'-UTR of p21 transcript in vitro and in vivo to regulate p21 mRNA stability. Taken together, we revealed that PCBP4 regulates both basal and stress-induced p21 expression through binding p21 3'-UTR and modulating p21 mRNA stability.


Optimal design of permeable fiber network structures for fog harvesting.
Fog represents a large untapped source of potable water, especially in arid climates. Numerous plants and animals use textural and chemical features on their surfaces to harvest this precious resource. In this work, we investigate the influence of the surface wettability characteristics, length scale, and weave density on the fog-harvesting capability of woven meshes. We develop a combined hydrodynamic and surface wettability model to predict the overall fog-collection efficiency of the meshes and cast the findings in the form of a design chart. Two limiting surface wettability constraints govern the re-entrainment of collected droplets and clogging of mesh openings. Appropriate tuning of the wetting characteristics of the surfaces, reducing the wire radii, and optimizing the wire spacing all lead to more efficient fog collection. We use a family of coated meshes with a directed stream of fog droplets to simulate a natural foggy environment and demonstrate a five-fold enhancement in the fog-collecting efficiency of a conventional polyolefin mesh. The design rules developed in this work can be applied to select a mesh surface with optimal topography and wetting characteristics to harvest enhanced water fluxes over a wide range of natural convected fog environments.


Pathogenesis of Collagen-Induced Arthritis: Role of Immune Cells with Associated Cytokines and Antibodies, Comparison with Rheumatoid Arthritis.
Collagen-induced arthritis is the most com-mon in vivo model of rheumatoid arthritis used for investigation of new potential therapies in preclinical research. Rheumatoid arthritis is a systemic inflammatory and autoimmune disease affecting joints, accompanied by significant extra-articular symptoms. The pathogenesis of rheumatoid arthritis and collagen-induced arthritis involves a so far properly unexplored network of immune cells, cytokines, antibodies and other factors. These agents trigger the autoimmune response leading to polyarthritis with cell infiltration, bone and cartilage degeneration and synovial cell proliferation. Our review covers the knowledge about cytokines present in the rat collagen-induced arthritis model and the factors affecting them. In addition, we provide a comparison with rheumatoid arthritis and a description of their important effects on the development of both diseases. We discuss the crucial roles of various immune cells (subtypes of T and B lymphocytes, dendritic cells, monocytes, macrophages), fibroblast-like synoviocy-tes, and their related cytokines (TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, IL-23, GM-CSF, TGF-β). Finally, we also focus on key antibodies (rheu-matoid factor, anti-citrullinated protein antibodies, anti-collagen II antibodies) and tissue-degrading enzymes (matrix metalloproteinases).


Exploring seasonality in catatonia diagnosis: Evidence from a large-scale population study.
Catatonia is a severe psychomotor syndrome mainly associated with psychiatric disorders, such as mood disorders and schizophrenia. Seasonal patterns have been described for these psychiatric disorders, and a previous study conducted in South London showed for the first time a seasonal pattern in the onset of catatonia. In this study, we aim to extend those findings to a larger national sample of patients admitted to French metropolitan hospitals, between 2015 and 2022, and to perform subgroup analyses by the main associated psychiatric disorder. A total of 6225 patients diagnosed with catatonia were included. A seasonal pattern for catatonia diagnosis was described, using cosinor models. Two peaks of diagnoses for catatonic cases were described in March and around September-October. Depending on the associated psychiatric disorder, the seasonality of catatonia diagnosis differed. In patients suffering with mood disorders, peaks of catatonia diagnosis were found in March and July. For patients suffering with schizophrenia, no seasonal pattern was found.


Mechanical characterization of nacre as an ideal-model for innovative new endoprosthesis materials.
To mimic the impressive mechanical behavior of natural ceramics for technical or biomedical applications, interest has been focused on nacre, a natural composite consisting of imbricated aragonite platelets embedded in a protein matrix. Nacre is an ideal model material for implants, since it possesses favorable strength and toughness properties compared to the component materials of which it is composed. The focus of the present study was to test standardized parameters which are good indicators of the material's suitability as an implant material. A three-point bending test was performed on polished nacre samples according to international standards for Young's modulus, bending strength and fracture toughness. A total of 60 nacre samples were tested, with 5 samples each in 4 states of hydration (dry, distilled water, 0.9% NaCl and sea water). As a basis for comparison, 10 samples of a newly developed bioceramic material were tested for fracture toughness. The fracture toughness of nacre tended to be higher for specimens conditioned in 0.9% NaCl than for dry specimens (5.3 ± 0.6 vs. 4.3 ± 0.7 MPam(1/2), p = 0.061). The fracture toughness of the bioceramic investigated was observed to be somewhat higher than nacre (5.8 ± 0.4 vs. 4.3 ± 0.7 MPam(1/2), p ≤ 0.001). The increase in fracture toughness of hydrated nacre was not as large as would be expected based on the difference in stiffness of the matrix material after hydration that has been reported. Modulus and toughness were similar to published values and the fracture toughness observed was somewhat higher than reported for alumina implant ceramics, which are in use in total hip arthroplasty. In a direct comparison, we found that a newly developed alumina bioceramic material can in fact match nature in terms of fracture toughness.


The effect of feeding Streptococcus faecium upon Escherichia coli induced diarrhea in gnotobiotic pigs.
Streptococcus faecium (Sf) was fed to gnotobiotic pigs to control colibacillosis. Three strains of Escherichia coli (Ec) were used. Strain 0:K103,987p:NM of Ec fed to pigs without Sf developed severe diarrhea which persisted for several days. Those pigs given Sf and Ec had less diarrhea, recovered earlier, and had better weight gains than Ec only pigs. Two other strains of Ec (0157:K88ac:H19 and 08:K87,K88ab:H19) which were more virulent developed severe diarrhea and death in 5 of 8 pigs given Ec only. Those fed Sf and challenged with Ec developed some diarrhea, but the pigs gained weight and none of the pigs died. Bacterial counts of Ec and Sf from 3 different levels of small intestine and cecum were comparable. The counts were reduced for both organisms in those pigs with dual colonization. It would appear that feeding Sf reduced the toxic effect of Ec and prevented a generalized infection and death. Forty-eight litters of surgically-obtained colostrum-deprived specific-pathogen-free (SPF) pigs for repopulating swine production units were started on Sf probiotic; 48 preceding litters not fed Sf were used for comparison. Those fed Sf had a mortality rate of 8.5% as compared to 18% for those not fed Sf.


Submodality distribution in sensorimotor cortex of the unanesthetized monkey.
1. Neuronal responses to cutaneous and noncutaneous stimulation were examined in the hindlimb representation of the precentral motor cortex (MI) and the first somatosensory cortex (SI) of unanesthetized monkeys. 2. MI can be divided into two distinct parts of the basis of its afferent input. The rostral part receives predominantly noncutaneous inputs, while the cutaneous input is primarily confined to the caudal part of MI. Thus, a differential distribution of submodality groups exists in the MI cortex. Caudal to MI, area 3a responds mainly to stimulation of noncutaneous receptors, in marked contrast to the caudal part of MI or area 3b. 3. The finding of a differential distribution of cutaneous inputs within MI is of significance a) to hypotheses concerning the role of somatosensory input to the MI cortex, b) to studies that attempt to characterize somatosensory inputs to MI by the proportion of neurons responsive to cutaneous and noncutaneous stimulation, and c) in that they confirm and extend similar findings recently reported for the forelimb representation of an anesthetized New World monkey (43).


Social Support and Psychological Distress among the Bedouin Arab Elderly in Israel: The Moderating Role of Gender.
In Israel, as in other developed countries, mental health problems are common among older adults who are members of disadvantaged ethnic minorities that are experiencing cultural and social changes. The main goals of the current study were: (a) to examine gender differences in the levels of psychological distress and social support among Bedouin elders, and (b) to examine the moderating role of gender in the associations between social support indices and psychological distress. We used a cross-sectional design, and independent t-tests and hierarchical linear regression analysis were performed. The study was conducted in homes and in social clubs and community centers for elderly people and involved face-to-face interviews and self-administered questionnaires. A convenience sample of 170 Bedouin Arab elderly people living in Israel participated in the study. Participants completed self-report questionnaires that assessed psychological distress, perceived social support, instrumental social support, and socio-demographic characteristics. Male elders reported lower levels of psychological distress and higher levels of instrumental support. Female elders, who reported low levels of both perceived and instrumental support, also reported higher levels of psychological distress. Among the women, there were significant associations between psychological distress and perceived social support, and instrumental support only when the levels of support were low. This study underscores the moderating role of gender in the associations between different types of social support and psychological distress among elderly people belonging to ethnic and cultural underprivileged minority groups.


Potential value of cefoperazone in bacterial meningitis: experimental studies.
To assess the potential value of cefoperazone in treating bacterial meningitis, its pharmacokinetics in the cerebrospinal fluid of rabbits were studied. Cefoperazone penetrated poorly into the cerebrospinal fluid of rabbits with uninflamed meninges, but in the presence of meningitis concentrations increased 2- to 3-fold. These concentrations were above the minimum inhibitory concentrations for the majority of Enterobacteriaceae, indicating the potential value of cefoperazone in treating bacterial meningitis. The half-lives of cefoperazone and moxalactam in cerebrospinal fluid, measured by a bioassay, were marked prolonged by meningeal inflammation. In contrast, the half-life of cefotaxime in cerebrospinal fluid was short. Consequently both cefoperazone and moxalactam provided significantly better antibacterial effect in cerebrospinal fluid than did cefotaxime.


Structure of the FIRA gene of Plasmodium falciparum.
The falciparum interspersed repeat antigen (FIRA) plays a dominant role in the human antibody response to the malaria parasite Plasmodium falciparum. We have therefore determined the complete sequence of a genomic clone encoding FIRA. The FIRA gene contains a single intervening sequence, located immediately 3' to the putative hydrophobic core of a signal sequence in the short (100 amino acids) exon 1. The second exon largely encodes blocks of 13 hexapeptide repeats based loosely on the consensus sequence Pro-Val-Thr-Thr-Gln-Glu. The first block encoded 39 hexapeptides followed by about nine blocks of 13 hexapeptides interspersed between a conserved region of 81 amino acids, which is itself repeated along the molecule. Although deletions of repeats in this and four other independent clones make the exact number of blocks uncertain, this structure is supported by genomic blotting studies. As 31 variants of the repeat have been identified so far, we suggest that this extreme repeat variability must have important implications for the host immune response.


The fear factor in healthcare: employee information sharing.
This study looks at employee information sharing among hospitals, a topic that is underresearched, underreported, and under the radar for most healthcare leaders. We initiated the research under the assumption that executives in healthcare are reluctant to share employment reference information about staff beyond the employee's name, dates of employment, and position held. We believed executives take this precaution because they fear being sued by the employee for defamation. However, not obtaining the necessary and critical information to hire a competent employee can open the potential employer up to a negligence lawsuit if it hires someone who jeopardizes the safety of patients or staff. Hence, the hiring organization faces a double-edged sword: On one side, it cannot get the critical information on a potential applicant from the previous employer due to a culture of "fear in sharing" information; on the other side, if it unwittingly hires a poor or dangerous applicant who threatens safety, it runs the risk of a negligence lawsuit for failure to ascertain information before the hire. Prior studies demonstrate that the likelihood of a successful defamation lawsuit is low and information sharing of factual incidents is unlikely to result in successful lawsuits. Why, then, are healthcare executives unwilling to provide comprehensive references when they should be aware that sustaining a culture of silence increases the potential for hiring a bad employee and seriously jeopardizes the security and safety of patients, other staff, and the public? This article's primary contribution to the literature is to offer the first nationwide study to empirically test the current levels of employee information sharing among hospitals. It is also the first study to focus exclusively on healthcare. Furthermore, this research considers factors that might influence executives in their willingness to share employee reference information. The study reveals that a culture of silence is pervasive among hospitals. Although many hospital executives are reluctant to share information, they tend to overestimate the likelihood of being sued (successfully or otherwise) by previous employees for defamation. In addition, this study shows that some hospital executives share negative information about former employees but may do so off the record.


Surface-Immobilized Photoinitiators for Light Induced Polymerization and Coupling Reactions.
Straightforward and versatile surface modification, functionalization and coating have become a significant topic in material sciences. While physical modification suffers from severe drawbacks, such as insufficient stability, chemical induced grafting processes efficiently modify organic and inorganic materials and surfaces due to covalent linkage. These processes include the "grafting from" method, where polymer chains are directly grown from the surface in terms of a surface-initiated polymerization and the "grafting to" method where a preformed (macro)-molecule is introduced to a preliminary treated surface via a coupling reaction. Both methods require an initiating species that is immobilized at the surface and can be triggered either by heat or light, whereas light induced processes have recently received increasing interest. Therefore, a major challenge is the ongoing search for suitable anchor moieties that provide covalent linkage to the surface and include initiators for surface-initiated polymerization and coupling reactions, respectively. This review containing 205 references provides an overview on photoinitiators which are covalently coupled to different surfaces, and are utilized for subsequent photopolymerizations and photocoupling reactions. An emphasis is placed on the coupling strategies for different surfaces, including oxides, metals, and cellulosic materials, with a focus on surface coupled free radical photoinitiators (type I and type II). Furthermore, the concept of surface initiation mediated by photoiniferters (PIMP) is reviewed. Regarding controlled radical polymerization from surfaces, a large section of the paper reviews surface-tethered co-initiators, ATRP initiators, and RAFT agents. In combination with photoinitiators or photoredox catalysts, these compounds are employed for surface initiated photopolymerizations. Moreover, examples for coupled photoacids and photoacid generators are presented. Another large section of the article reviews photocoupling and photoclick techniques. Here, the focus is set on light sensitive groups, such as organic azides, tetrazoles and diazirines, which have proven useful in biochemistry, composite technology and many other fields.


Improving communication between patients and providers using health information technology and other quality improvement strategies: focus on Asian Americans.
Disparities in provider-patient communication have been shown to exist among Asian Americans, especially those who are low-income and have limited English proficiency. These disparities have resulted in unmet health care needs and poor quality care. To identify strategies for improving provider-patient communication in this population, we conducted a systematic review of the literature and in-depth interviews with key informants. Little published literature on interventions focused on Asian Americans was found. Most interventions were conducted among White populations and occurred in the waiting room before patients' visits with their providers. Interventions ranged from a leaflet encouraging patients to ask more questions, to more intensive face-to-face coaching before office visits. Health information technology (health IT) has not been widely used to improve communication, especially among patients with limited English proficiency. More research is needed using new health IT strategies to improve care for Asian Americans and other vulnerable populations.


Combined saphenous and sciatic catheters for analgesia after major ankle surgery: a double-blinded randomized controlled trial.
Continuous sciatic nerve block is used for pain management following major ankle surgery. Pain from the saphenous nerve territory often persists. We conducted a double-blinded randomized placebo-controlled trial to evaluate the effect of a supplementary saphenous catheter in the proximal thigh combined with a popliteal sciatic catheter and single-shot saphenous nerve block after major ankle surgery. Fifty patients received both sciatic and saphenous continuous catheters inserted along the short axis of the nerves with ultrasound-guidance. All patients had an initial sciatic nerve block followed by a continuous sciatic catheter infusion and an initial saphenous nerve block with ropivacaine. Participants were then randomized to infusion of either ropivacaine or isotonic saline in the saphenous catheter for 48 hr postoperatively. The primary outcome was total intravenous morphine consumption during the first 48 hr postoperatively. Secondary outcomes were clinical analgesia, saphenous analgesia, territory of worst pain, and patient satisfaction. Forty-four patients were included in the analysis. The mean (SD) 48-hr morphine consumption was 24.7 (21.6) mg in the intervention group and 27.8 (20.1) mg in the placebo group (P = 0.63). The mean difference in 48-hr morphine consumption was 3.0 mg (95% confidence interval, -9.7 to 15.7). There were no differences regarding the secondary outcomes. A saphenous catheter with a low-dose continuous infusion of ropivacaine, as an adjunct to a sciatic catheter, had no effect on the postoperative analgesia after major ankle surgery when both catheters were inserted along the short axis of the nerves. This trial was registered at ClinicalTrials.gov (NCT01445210).


Salinity promotes accumulation of 3-dimethylsulfoniopropionate and its precursor S-methylmethionine in chloroplasts.
Wollastonia biflora (L.) DC. plants accumulate the osmoprotectant 3-dimethylsulfoniopropionate (DMSP), particularly when salinized. DMSP is known to be synthesized in the chloroplast from S-methylmethionine (SMM) imported from the cytosol, but the sizes of the chloroplastic and extrachloroplastic pools of these compounds are unknown. We therefore determined DMSP and SMM in mesophyll protoplasts and chloroplasts. Salinization with 30% (v/v) artificial seawater increased protoplast DMSP levels from 4.6 to 6.0 mumol mg-1 chlorophyll (Chl), and chloroplast levels from 0.9 to 1.9 mumol mg-1 Chl. The latter are minimum values because intact chloroplasts leaked DMSP during isolation. Correcting for this leakage, it was estimated that in vivo about one-half of the DMSP is chloroplastic and that stromal DMSP concentrations in control and salinized plants are about 60 and 130 mM, respectively. Such concentrations would contribute significantly to chloroplast osmoregulation and could protect photosynthetic processes from stress injury. SMM levels were measured using a novel mass-spectrometric method. About 40% of the SMM was located in the chloroplast in unsalinized W. biflora plants, as was about 80% in salinized plants; the chloroplastic pool in both cases was approximately 0.1 mumol mg-1 Chl. In contrast, > or = 85% of the SMM was extrachloroplastic in pea (Pisum sativum L.) and spinach (Spinacia oleracea L.), which lack DMSP. DMSP synthesis may be associated with enhanced accumulation of SMM in the chloroplasm.


Failures in children's protection in Newfoundland and Labrador: from the Hughes (1991) to Markesteyn and Day (2006) inquiries and beyond.
The death in 2003 of Zachary Turner, a child in receipt of children's protection services in Foxtrap, Newfoundland, sparked an independent inquiry into his death. Subsequently, other reviews were completed of children's protection services. These were not the first reviews or inquiries of this kind in Newfoundland and Labrador. In 1991, Justice Samuel Hughes had conducted a public inquiry into children's protection services. This article is a critical historical analysis of selected aspects of children's protection services. The authors uncover repeated failures by government in its child protection systems and discuss implications for future concerns.


Approaches to the ankle region.
This article has attempted to address the surgical realm of the ankle region. With the advent of more interest in treating patients who require atraumatic and corrective surgical procedures of the ankle region, it is mandatory for us to become better trained and to improve our skills and expertise. The points worth summarizing in the surgical approach to the ankle region are a complete anatomic knowledge, basic principles of lines of tension, thorough understanding of biomechanics, and good preoperative judgment. The atraumatic approach was presented by describing how to accomplish this objective--by protecting neurovascular bundles, by following normal skin lines or creases, by avoiding scars over a bony prominence, and by avoiding incisions on a weight-bearing surface. Certain basic anatomic and physiologic principles were stated, such as making incisions large enough, using tourniquets when possible, avoiding excessive and unnecessary dissection, and avoiding stretching, crushing, or allowing tissue to dry. Various approaches for surgical procedures to the ankle region were given. The approaches described the location of the incision, the anatomy to be seen while deepening the wound, and the reason for the surgical procedure.


Predicting factors of present hepatitis C virus infection among patients positive for the hepatitis C virus antibody.
To identify the predicting factors of present hepatitis C virus (HCV) infection among patients with positivity for antibodies to HCV (anti-HCV). We analyzed patients who showed positive enzyme immunoassay (EIA) results and performed an HCV RNA test as a confirmatory test at Kyung Hee University Hospital at Gangdong from June 2006 to July 2012. The features distinguishing the groups with positive and negative HCV RNA results were reviewed. In total, 490 patients were included. The results of the HCV RNA test were positive and negative in 228 and 262 patients, respectively. The index value of anti-HCV, mean age, platelet counts, total bilirubin, prothrombin time international normalized ratio, albumin and alanine transaminase (ALT) levels differed significantly between the two groups. On multivariable analysis, an index value of anti-HCV >10 [odds ratio (OR)=397.27, P<0.001), ALT >40 IU/L (OR=3.64, P=0.001), and albumin <3.8 g/dL (OR=2.66, P=0.014) were related to present HCV infection. Although EIA is not a quantitative test, considering the anti-HCV titer with ALT and albumin levels may be helpful in predicting present of HCV infection.


Conservative treatment modalities in retinoblastoma.
Retinoblastoma is the most common primary intraocular malignancy of childhood. A potentially curable cancer, its treatment has improved significantly over the last few decades. The purpose of this article is to review the literature on various conservative treatment modalities available for the treatment of retinoblastoma and their effectiveness, when used alone or in combination. Pubmed, Medline, Embase, and the Cochrane library were searched through 2012 for published peer reviewed data on conservative treatment modalities for retinoblastoma. Various studies show that while enucleation remains the standard of care for advanced intraocular tumors, conservative modalities that can result in globe salvage and preservation of useful vision are being increasingly employed. Such modalities include systemic chemotherapy, focal consolidation with transpupillary thermotherapy, laser photocoagulation and cryotherapy, plaque brachytherapy, and delivery of local chemotherapy using subconjunctival, sub-tenon, or intra-arterial routes. When used alone or in combination, these treatment modalities can help in avoidance of external beam radiotherapy or enucleation, thus reducing the potential for long-term side effects, while salvaging useful vision. Radioactive plaque brachytherapy has an established role in selected patients with intraocular retinoblastoma. Local injections of chemotherapeutic agents via the sub-tenon or sub-conjunctival route have been used with varying degrees of success, usually as an adjunct to systemic chemotherapy. Intra-arterial ophthalmic artery delivery of melphalan has shown promising results. It is important to recognize that today, several treatment options are available that can obviate the need for enucleation, and cure the cancer with preservation of functional vision. A thorough knowledge and understanding of these conservative treatment modalities is essential for appropriate management.


Changes in the Photoluminescence of Monolayer and Bilayer Molybdenum Disulfide during Laser Irradiation.
Various postsynthesis processes for transition metal dichalcogenides have been attempted to control the layer number and defect concentration, on which electrical and optical properties strongly depend. In this work, we monitored changes in the photoluminescence (PL) of molybdenum disulfide (MoS2) until laser irradiation generated defects on the sample flake and completely etched it away. Higher laser power was required to etch bilayer MoS2 compared to monolayer MoS2. When the laser power was 270 μW with a full width at half-maximum of 1.8 μm on bilayer MoS2, the change in PL intensity over time showed a double maximum during laser irradiation due to a layer-by-layer etching of the flake. When the laser power was increased to 405 μW, however, both layers of bilayer MoS2 were etched all at once, which resulted in a single maximum in the change of PL intensity over time, as in the case of monolayer MoS2. The dependence of the etching pattern for bilayer MoS2 on laser power was also reflected in position changes of both exciton and trion PL peaks. The subtle changes in the PL spectra of MoS2 as a result of laser irradiation found here are discussed in terms of PL quantum efficiency, conversion between trions and excitons, mean interatomic spacing, and the screening of Coulomb interaction.


Effect of enrofloxacin therapy on shipping fever pneumonia in feedlot cattle.
The effect of enrofloxacin therapy was investigated in 110 male double-muscled cattle weighing 275 +/- 3 kg, during a spontaneous outbreak of shipping fever occurring 11 +/- 2 days after they arrived in the feedlot. Forty-six diseased animals were divided randomly into three groups A, B and C, containing 17, 19 and 10 animals, respectively; the animals in group A were injected intramuscularly once daily for three consecutive days with 2.5 mg/kg of enrofloxacin, those in group B with 5 mg/kg of enrofloxacin and those in group C with 10 mg/kg of oxytetracycline. Clinical, serological, production and respiratory functional observations were recorded. The animals were clinically cured after the three day treatment except for three in group A and two in group C. These five animals made a clinical recovery after a three day booster treatment with a dose of 5 mg/kg enrofloxacin. The changes in respiratory gas exchange values induced by shipping fever were completely reversed 15 days later, suggesting that there had been no irreversible lung damage. The daily weight gains and the arterial blood gas values of the three groups of treated cattle were not significantly different. The high efficacy of the low dosage of enrofloxacin in this clinical syndrome may be explained by its antibacterial activity against Pasteurella species and Mycoplasma species. This field trial supports the in vitro studies which suggested than enrofloxacin is an appropriate therapy in cases of shipping fever.


Pharmacology of vascular endothelium. Delivered on 27 June 2004 at the 29th FEBS Congress in Warsaw.
Sir John Vane named vascular endothelium 'the maestro of blood circulation'. Recently, 'the maestro' has become a target for pharmacotherapy of atherothrombotic and diabetic vasculopathies with well known cardio-vascular drugs belonging to the families of Angiotensin Converting Enzyme inhibitors, HMG CoA reductase inhibitors or beta1-Adrenoceptor antagonists. These drugs became upgraded to a position of the pleiotropic endothelial drugs. It is not a simple verbal change in the nomenclature. It means that these drugs apart from their well defined mechanisms of action, as indicated in their regular names, in addition they act in an unknown mechanism at the level of vascular endothelium preventing angina, myocardial infarction and stroke. Many biochemical events take place in endothelial cells. I chose for a closer inspection the nitric oxide/prostacyclin defensive system to explain the endothelial pleiotropism of the drugs in question. I tried to examine the validity of this conception according to the general rule: in vitro cognitio sed in vivo veritas.


Chidamide, Decitabine, Cytarabine, Aclarubicin, and Granulocyte Colony-stimulating Factor Therapy for Patients with Relapsed/Refractory Acute Myeloid Leukemia: A Retrospective Study from a Single-center.
Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia. However, their efficacy in patients with relapsed/refractory acute myeloid leukemia (R/R AML) remains unclear. Clinical data of R/R AML patients who received a CDCAG regimen (chidamide, decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulating factor) from July 1, 2018 to October 31, 2021 at our center were retrospectively assessed, and the safety and efficacy of the CDCAG regimen were evaluated. Patients were followed up until November 30, 2021, with a median follow-up of 21.6 months (95% CI: 10.0-33.2 months). A total of 67 patients were enrolled. Two patients died within 3 weeks after the initiation, and therefore only 65 patients underwent the assement for clinical response and survival. It was found that 56.9% patients achieved complete remission with a median overall survival (OS) of 9.6 months. The median OS of responders was 25.9 months, while that of non-responders was 5.0 months (P<0.0001). Patients with gene mutations had a superior overall response rate (ORR) (80.4% vs. 45.5%, P=0.043) compared to those without gene mutations. The presence of DNA methyltransferase 3 A (DNMT3A), ten-eleven translocation-2 (TET2), and isocitrate dehydrogenase 1/2 (IDH1/2) mutations did not affect the response rate (88.2% vs. 68.9%, P=0.220) and reflected a better OS (not attained vs. 9.0 months, P=0.05). The most common non-hematologic adverse events were pulmonary infection (73.1%), followed by febrile neutropenia (23.9%) and sepsis (19.4%). The CDCAG regimen was effective and well-tolerated in R/R AML patients, increasing the potential for allogeneic hematopoietic stem cell transplantation. Moreover, patients with DNMT3A, TET2, and IDH1/2 mutations might benefit from this regimen.


Endovascular GDC Treatment of an Idiopathic Carotid-Cavernous Fistula Caused by Aneurysmal Rupture of the Intra-Cavernous Carotid Artery. Case Report.
Aneurysmal rupture of the intra-cavernous carotid artery may cause idiopathic carotid-cavernous fistula (CCF), and the treatment choice for occluding shunting fistula in this type of CCF is an endovascular approach using detachable balloons. However, little has been reported on treating such lesions with the intra-aneurysmal embolization using Guglielmi detachable coils (GDCs).To our knowledge, ours is the first reported case of successful treatment by selective intra-fistula and intra-aneurysmal embolization with GDCs. A 74-year-old woman exhibited proptosis and chemosis of her left eye over a period of one month. Symptoms of double vision in conversion and pulsatile murmur in her left eye were also noted. Angiography revealed an intra-cavernous aneurysm of the left internal carotid artery (ICA) with a shunting fistula, which drained into the dilated cavernous sinus, superior orbital vein (SOV), superior petrosal sinus, inferior petrosal sinus, and pterygoid plexus.We thought the fistula would occlude by intra-aneurysmal embolization, but we had no confidence of tight packing of the aneurysm since the aneurismal neck was relatively wide. So, we embolized the venous side of the shunting fistula and then the dome of the aneurysm with GDCs. Immediately after the operation, her symptoms and signs were ameliorated, and complete occlusion of the CCF was observed on long-term follow-up. We suggest selective intrafistula and intra-aneurysmal embolization with GDCs as an alternative method of treatment of idiopathic CCF originating from aneurysmal rupture of the intra-cavernous carotid artery.


Dynamic contrast-enhanced and diffusion MRI show rapid and dramatic changes in tumor microenvironment in response to inhibition of HIF-1alpha using PX-478.
PX-478 is a new agent known to inhibit the hypoxia-responsive transcription factor, HIF-1alpha, in experimental tumors. The current study was undertaken in preparation for clinical trials to determine which noninvasive imaging endpoint(s) is sensitive to this drug's actions. Dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) magnetic resonance imaging (MRI) were used to monitor acute effects on tumor hemodynamics and cellularity, respectively. Mice bearing human xenografts were treated either with PX-478 or vehicle, and imaged over time. DW imaging was performed at three b values to generate apparent diffusion coefficient of water (ADCw) maps. For DCE-MRI, a macromolecular contrast reagent, BSA-Gd-DTPA, was used to determine vascular permeability and vascular volume fractions. PX-478 induced a dramatic reduction in tumor blood vessel permeability within 2 hours after treatment, which returned to baseline by 48 hours. The anti-VEGF antibody, Avastin, reduced both the permeability and vascular volume. PX-478 had no effect on the perfusion behavior of a drug-resistant tumor system, A-549. Tumor cellularity, estimated from ADCw, was significantly decreased 24 and 36 hours after treatment. This is the earliest significant response of ADC to therapy yet reported. Based on these preclinical findings, both of these imaging endpoints will be included in the clinical trial of PX-478.


A Machine Learning Approach to Qualitatively Evaluate Different Granulation Phases by Acoustic Emissions.
Wet granulation is a frequent process in the pharmaceutical industry. As a starting point for numerous dosage forms, the quality of the granulation not only affects subsequent production steps but also impacts the quality of the final product. It is thus crucial and economical to monitor this operation thoroughly. Here, we report on identifying different phases of a granulation process using a machine learning approach. The phases reflect the water content which, in turn, influences the processability and quality of the granule mass. We used two kinds of microphones and an acceleration sensor to capture acoustic emissions and vibrations. We trained convolutional neural networks (CNNs) to classify the different phases using transformed sound recordings as the input. We achieved a classification accuracy of up to 90% using vibrational data and an accuracy of up to 97% using the audible microphone data. Our results indicate the suitability of using audible sound and machine learning to monitor pharmaceutical processes. Moreover, since recording acoustic emissions is contactless, it readily complies with legal regulations and presents Good Manufacturing Practices.


Antibody-dependent phagocytosis (ADP) responses following trivalent inactivated influenza vaccination of younger and older adults.
Globally the most commonly utilised immunisation against influenza is the trivalent inactivated influenza vaccine (TIV) derived from an A/H1N1, an A/H3N2 and aB type influenza virus. Vaccine effectiveness of TIV varies year to year, depending on how well antigenically matched the strains in the vaccine are compared to circulating strains [1,2]. Moreover, vaccine effectiveness can vary within certain subpopulations such as HIV-positive, young children and the elderly. Decreased vaccine effectiveness in the elderly is associated with impaired Ab production, as measured by standard hemagglutination inhibition (HAI) assays. We investigated the level of Antibody Dependent Phagocytosis (ADP)-mediating Abs induced by the 2008-TIV in healthy Australian adults aged over and under 60years to determine if this immune function was also reduced in the elderly. We utilised an ADP assay that measures the uptake of IgG-opsonised HA-coated fluorescent microspheres by a monocytic cell line. We also measured HA-specific Abs that are close enough to bind to dimeric FcγRIIa ectodomains in an ELISA-based assay. Furthermore, we compared the extent of cross-reactive recognition of diverse influenza strains by ADP-mediating Abs found in pre- and post-vaccination sera in both of these groups. We found that young adults and older adults mounted similar ADP activity against HAs contained in the 2008-TIV, despite older adults have diminished HI responses. The level of cross-reactive antibodies against other HAs was limited in both groups. We conclude that seasonal influenza vaccination elicits limited cross-reactive ADP to HA in both young and older adults. New influenza vaccination strategies that elicit cross-reactive and polyfunctional antibodies are needed.


Developing treatments for impaired cognition in schizophrenia.
Schizophrenia is one of the most debilitating of all common brain disorders, exacting a heavy toll on the afflicted and having a tremendous public health impact. Clinical outcome is more strongly predicted by cognitive deficits than psychotic symptoms, with no established treatment for these deficits. In this review, we discuss the status of treatment development for impaired cognition in schizophrenia. These treatments include a range of pharmacological targets within diverse neurotransmitter systems. New technologies, including transcranial magnetic stimulation and transcranial direct current stimulation, and psychological therapies, such as computer-based cognitive training, may also benefit cognition in schizophrenia. Each of these approaches shows promise and their integration may optimize benefits for patients in the future.


Factors related to the level of severity of asthma in primary care.
The severity of asthma varies in patients in primary care. The aim of this study was to identify factors related to asthma severity in a primary care setting. In this cross-sectional asthma study a random sample of 1477 patients, aged 15-45 years, from 42 primary health care centres received two questionnaires: one disease oriented and one quality of life oriented, MiniAQLQ. A classification of the asthma severity similar to the GINA guidelines was made with the information obtained from the questionnaire. The classification was based on current treatment, use of rescue medication, night symptoms, emergency consultations and use of oral steroids for treatment of exacerbations. Thirty-five per cent of the women and 24% of the men were classified as having severe asthma. Women used more inhaled corticosteroids, more often took long acting beta-2 agonists or a leukotrien antagonist in addition to corticosteroids, experienced more frequent night awakenings and were more often smokers than men. In a multivariable analysis, female sex increased the odds of having severe asthma by 60% as compared with male sex, age by 3% per year, not having the asthma prescription filled owing to cost by 59%, daily smoking by 66% and pollen allergy by 85%. Female sex, age, pollen and pet allergy, not having the asthma prescription filled owing to cost, and daily smoking were all independently associated with asthma severity.


The association between social support and self-rated health in midlife: are men more affected than women?
Social support from family and friends is recognized as an important social determinant of health, given its protective effects on individuals' physical and mental well-being. While most studies have focused on older adults, investigating midlife health is equally crucial since middle-aged individuals are also susceptible to the harmful health outcomes of inadequate social support from friends and family. This study contributes to the debate by examining whether social support is associated with self-rated health among middle-aged Brazilian adults and how this relationship varies between men and women. Using data from the nationwide Brazilian National Health Survey conducted in 2019, logistic regression models were employed to assess differences in self-rated health, accounting for confounding factors. The sample comprised 31,926 middle-aged adults, of which 52.5% were women. The overall prevalence of poor self-rated health was 40.7%, with a significant difference between men and women. Results from this study suggest that having no friends or family members to rely on, both during good and challenging times, was associated with poorer self-rated health. However, the strength of this association differs by gender, with social support from friends playing a more critical role in women's self-rated health. On the other hand, family support was associated with male self-rated health, particularly for men with three or more family members they can rely on. Future studies should consider cultural and contextual factors to better understand other dimensions of social support and its association with midlife health.


The power of talk: developing discriminatory group norms through discussion.
Research has shown that group discussion can increase intergroup prejudice and discrimination. However, we know little about the process by which discussion has this effect. Therefore, four studies were conducted in a real-world context to investigate this process. Results suggest that discussing a negative societal stereotype (relative to individual rumination in Studies 1 and 3 and alternative discussions in Studies 2 and 3) increases intentions to engage in discrimination against the out-group target of the stereotype. This is mediated by the formation of an in-group norm which supports discrimination (Study 1) and the extent to which the discussion validates the stereotype (Study 2). A fourth study manipulated the extent to which consensus on the negative stereotype was reached through discussion. When the discussion ended in consensus, participants have greater intention to undertake collective action against the stereotyped out-group, mediated by a congruent in-group norm. These results provide evidence that the process by which discussion increases intergroup discrimination is via the formation of discriminatory local group norms.


The role of ECG-gated MDCT in the evaluation of aortic and mitral mechanical valves: initial experience.
The objective of our study was to evaluate the role of ECG-gated MDCT in the functional evaluation of mechanical prosthetic aortic and mitral valves. Twenty sequential patients with 23 mechanical prosthetic valves were evaluated with an ECG-gated 40- or 64-MDCT scanner. Multiplanar reformation, maximal-intensity-projection, volume-rendering, and volume-averaging techniques were used for visualization of valve leaflets in systole and diastole. The visibility of each mechanical valve was evaluated by consensus of a radiologist and a cardiologist using a subjective 5-point scale (0-4). MDCT findings were correlated with fluoroscopic opening and closing angle measurements and echocardiographic pressure gradient measurements in 11 and 19 valves, respectively. The series included 18 bileaflet and five single-leaflet mechanical valves. The visibility score for the bileaflet mechanical valves was excellent (score of 4) in all 18 cases, but it was lower for single-leaflet valves (mean score, 2.8; range, 1-4) (p = 0.04). Bland-Altman plots showed high agreement between MDCT and fluoroscopy for measurements of opening and closing angles of bileaflet mechanical valves. In four patients, a stuck valve was seen on MDCT and was confirmed by fluoroscopy. Doppler echocardiography showed increased transvalvular pressure in two of the four patients with a stuck mitral valve and increased transaortic pressure in four patients with normal prosthetic aortic valve motion. Our preliminary results suggest that MDCT is a promising technique for functional evaluation of bileaflet mechanical valves, allowing reliable measurements of opening and closing leaflet angles. However, the role of MDCT in the evaluation of single-leaflet valves might be limited.


[Influence of protein molecule conformation on the character of its interaction with a phospholipid bilayer].
The adsorption of lysozyme on mixed phosphatidyl choline-cardiolipin vesicles was studied at pH 4.0 and 6.0. The binding constants at both pH were determined at 0 and 22 degrees C. The presence of maximum on the adsorption isotherm at pH 6.0 was interpreted as an indication of the formation of two types of the protein-lipid complexes. This interpretation was confirmed by electron-microscopic observations. On the other hand, at pH 4.0 only one type of the protein-lipid complex was formed. The lysozyme conformation in solution and in the protein-lipid complexes was studied by circular dichroism. It was found that at acidic pH the lysozyme molecule contains a higher per cent of alpha-helix segments than at neutral pH. As follows from the measurements of lysozyme distribution in two phase systems the increase in alpha-helicity results in the formation of hydrophobic patches on the surface of the protein molecule. The results of the present work and of the previous studies of the interaction of red- and oxy- form of cytochrome C with phospholipid allow the conclusion that for peripheral proteins the nature of protein-lipid interactions is determined by the protein alpha-helix content and by hydrophobic pattern of the protein molecule surface.


Mobile monitoring and spatial prediction of black carbon in Cairo, Egypt.
This study harnesses the power of mobile data in developing a spatial model for predicting black carbon (BC) concentrations within one of the most heavily populated regions in the Middle East and North Africa MENA region, Greater Cairo Region (GCR) in Egypt. A mobile data collection campaign was conducted in GCR to collect BC measurements along specific travel routes. In total, 3,300 km were travelled across a widespread 525 km of routes. Reported average BC values were around 20 µg/m3, announcing an alarming order of magnitude value when compared to the maximum reported values in similar studies. A bi-directional stepwise land use regression (LUR) model was developed to select the best combination of explanatory variables and generate an exposure surface for BC, in addition to a number of machine learning models (random forest gradient boost, light gradient boost model (LightGBM), Keras neural network (NN)). Data from 7 air quality (AQ) stations were compared-in terms of mean square error (MSE) and mean absolute error (MAE)-with predictions from the LUR and the NN model. The NN model estimated higher BC concentrations in the downtown areas, while lower concentrations are estimated for the peripheral area at the east side of the city. Such results shed light on the credibility of the LUR models in generating a general spatial trend of BC concentrations while the superiority of NN in BC accuracy estimation (0.023 vs 0.241 in terms of MSE and 0.12 vs 0.389 in terms of MAE; of NN vs LUR respectively).


A cyclic enzymatic amplification method for sensitive and selective detection of nucleic acids.
Based on Exonuclease III (Exo III) and displacing probes, we have developed a Cyclic Enzymatic Amplification Method (CEAM) for sensitive and selective detection of nucleic acids. In this design, the displacing probe is non-fluorescent on its own and cannot be digested by Exo III until displacement hybridization by a target sequence, leading to release of free non-quenched fluorophore. Because a single target sequence can lead to the release and digestion of numerous fluorophore strands from the displacing probe, a remarkable signal amplification is achieved. With this method, DNA can be detected in the picomolar range with a high selectivity and within less than 20 min.


Teaching specialty cancer medicine in rural hospitals: the cancer outreach program as a model.
Cancer doctors and nurses are clustered in the metropolitan areas of Virginia. However, cancer patients are found throughout the state, and cancer mortality time trends are worse in the rural areas. Efforts to recruit cancer physicians and nurses to rural hospitals have been unsuccessful due to the practice characteristics, educational isolation, and economic disincentives. Our rural cancer education program involves the physicians and nurses currently in practice at two rural hospitals. We provide hands-on training in cancer care, continuing education, and intense week-long educational sessions. We have observed changes in physician and nurse practice styles that benefit the cancer patient including effective pain management, enrollment of patients on clinical trials, increased use of adjuvant therapy, and breast conservation. We are providing state-of-the-art cancer care at the rural hospitals in the Cancer Outreach Program. We have improved the educational opportunities and increased utilization of the resources of the academic career center. We can modify the practice characteristics by providing needed clinical programs and enhancing the rural hospital/academic medical center link. We have shown that rural cancer care can be revenue-neutral or positive, and we are seeking creative solutions to the financial disincentives of rural specialty practice. We can assist the rural hospital in the recruitment of oncology specialty nurses and physicians by providing cancer care services, and the patient caseload is available to teach prospective rural subspecialty practitioners at the rural hospitals.


Polo-like kinase 1 activated by the hepatitis B virus X protein attenuates both the DNA damage checkpoint and DNA repair resulting in partial polyploidy.
Hepatitis B virus X protein (pX), implicated in hepatocarcinogenesis, induces DNA damage because of re-replication and allows propagation of damaged DNA, resulting in partial polyploidy and oncogenic transformation. The mechanism by which pX allows cells with DNA damage to continue proliferating is unknown. Herein, we show pX activates Polo-like kinase 1 (Plk1) in the G(2) phase, thereby attenuating the DNA damage checkpoint. Specifically, in the G(2) phase of pX-expressing cells, the checkpoint kinase Chk1 was inactive despite DNA damage, and protein levels of claspin, an adaptor of ataxia telangiectasia-mutated and Rad3-related protein-mediated Chk1 phosphorylation, were reduced. Pharmacologic inhibition or knockdown of Plk1 restored claspin protein levels, Chk1 activation, and p53 stabilization. Also, protein levels of DNA repair protein Mre11 were decreased in the G(2) phase of pX-expressing cells but not with Plk1 knockdown. Interestingly, in pX-expressing cells, Mre11 co-immunoprecipitated with transfected Plk1 Polo-box domain, and inhibition of Plk1 increased Mre11 stability in cycloheximide-treated cells. These results suggest that pX-activated Plk1 by down-regulating Mre11 attenuates DNA repair. Importantly, concurrent inhibition of Plk1, p53, and Mre11 increased the number of pX-expressing cells with DNA damage entering mitosis, relative to Plk1 inhibition alone. By contrast, inhibition or knockdown of Plk1 reduced pX-induced polyploidy while increasing apoptosis. We conclude Plk1, activated by pX, allows propagation of DNA damage by concurrently attenuating the DNA damage checkpoint and DNA repair, resulting in polyploidy. We propose this novel Plk1 mechanism initiates pX-mediated hepatocyte transformation.


The spinal cord as a site of opioid effects on gastrointestinal transit in the mouse.
Intrathecal (i.t.) administration of morphine (1, 3 or 10 micrograms) effectively inhibited the passage of a radiolabeled marker through the gastrointestinal tract of mice. This effect was reversed by pretreatment with naloxone (2 mg/kg s.c.). Transection of the spinal cord at the level of the second thoracic vertebra (T2) slowed control transit when measured after 4 hr; nevertheless, i.t. morphine inhibited transit in these paralyzed animals. Similarly, i.c.v. administration of morphine (1, 3 or 10 micrograms) inhibited transit regardless of whether the spinal cord was transected at T2. Lower efficacy was seen with i.p. (10-300 micrograms/kg) or i.v. (10 micrograms) morphine than with comparable doses given i.t. (10 micrograms). Intrathecal administration (1, 3 or 10 micrograms) of the proposed selective delta opioid agonist peptides, D-Ala2-D-Leu5-enkephalin, D-Pen2-L-Cys5-enkephalin or i.t. administration of D-Ser2-Leu-enkephalin-(Thr6) (10 micrograms) were effective in inhibiting gastrointestinal transit. In contrast, the proposed kappa agonists, ketocyclazocine (1, 3 or 10 micrograms) or dynorphin-(1-13) (1, 10 or 100 micrograms), did not affect transit after i.t. administration. Dynorphin-(1-13) (10, 30 or 100 micrograms) or dynorphin-(1-9) (10, 30 or 100 micrograms) similarly did not affect transit after i.c.v. administration. Whereas D-Ala2-D-Leu5-enkephalin (1, 3 or 10 micrograms) and D-Ser2-Leu-enkephalin-(Thr6) (10 micrograms) were also efficacious in inhibiting transit by the i.c.v. route, the more delta selective D-Pen2-L-Cys5-enkephalin (1, 3, 10 or 20 micrograms) was not.(ABSTRACT TRUNCATED AT 250 WORDS)


Is foot reflexology effective in reducing colic symptoms in infants: A randomized placebo-controlled trial.
Infantile colic and its accompanying crying represent a major source of stress and have negative physiological, emotional and psychological effects on infants and parents. The aim of this study was to examine the efficacy of foot reflexology for reducing symptoms of infantile colic. The study was conducted as a single-blind, randomized, placebo-controlled trial with a sample population of 45 infants diagnosed with infantile colic. Simple randomization was used to select a reflexology (study) group (n = 20) and a placebo group of infants with colic (n = 25). The parents and biostatistician were blinded to group assessment. Foot reflexology, or stimulating reflex points on the foot, was implemented with the reflexology group. Placebo foot reflexology, or noneffective touch, was used with the placebo group. Over a two-week period, both interventions were performed four times for 20 min each time by the researcher. The researcher collected data using the information form, the Infant Colic Scale (ICS), and a diary of daily crying duration. The trial ended with the completion of the data. In each group, 20 infants were studied. The means of the Infant Colic Scale scores and daily crying duration were significantly lower in the foot-reflexology group than in the placebo foot-reflexology group (p < .001). Infants with colic in the reflexology group cried less and experienced fewer symptoms than before treatment. Foot reflexology is a non-invasive and safe nursing intervention that is effective for reducing crying duration and symptoms in infants with colic.


Facial nerve schwannomas of the cerebellopontine angle: the mayo clinic experience.
Background There is often controversy regarding the optimal management for patients with facial nerve schwannomas (FNSs) of the cerebellopontine angle (CPA). Methods The clinical and radiological outcomes in 14 patients with CPA FNS were retrospectively reviewed. Results Patients underwent resection with anatomic nerve preservation (n = 3), facial-hypoglossal nerve anastomosis (n = 4), gamma knife radiosurgery (GKS) (n = 6), or observation (n = 1). A total of 83% of tumors that underwent GKS were stable or decreased in size. No patient who underwent resection showed evidence of tumor recurrence; the tumor under observation remained unchanged with normal facial function at the time of the last follow-up. Facial function was decreased in 57%, stable in 14%, and improved in 29% of those who underwent microsurgery. A total of 67% of patients who underwent GKS had stable facial function. Serviceable hearing was maintained in 50% of patients in the GKS group and 67% of the tumor resection group. Mean and median follow-up was 48 and 43 months, respectively (range, 12 to 95 months). Conclusion Observation should be the primary management when encountered with FNS of the CPA in those with good neurologic function. Microsurgery or radiosurgery may be used in those with poor facial function or tumor progression.


Robust landscapes of ribosome dwell times and aminoacyl-tRNAs in response to nutrient stress in liver.
Translation depends on messenger RNA (mRNA)-specific initiation, elongation, and termination rates. While translation elongation is well studied in bacteria and yeast, less is known in higher eukaryotes. Here we combined ribosome and transfer RNA (tRNA) profiling to investigate the relations between translation elongation rates, (aminoacyl-) tRNA levels, and codon usage in mammals. We modeled codon-specific ribosome dwell times from ribosome profiling, considering codon pair interactions between ribosome sites. In mouse liver, the model revealed site- and codon-specific dwell times that differed from those in yeast, as well as pairs of adjacent codons in the P and A site that markedly slow down or speed up elongation. While translation efficiencies vary across diurnal time and feeding regimen, codon dwell times were highly stable and conserved in human. Measured tRNA levels correlated with codon usage and several tRNAs showed reduced aminoacylation, which was conserved in fasted mice. Finally, we uncovered that the longest codon dwell times could be explained by aminoacylation levels or high codon usage relative to tRNA abundance.


Innovations and advances in brachytherapy.
The treatment of cancer with radioactive sources using topical molds and intracavitary radium showed the efficacy of brachytherapy long before external radiation therapy became common practice. Brachytherapy is progressing in several clinical directions that reflect technological innovation as well as changes in medical care which combine to provide significant advances in the practice of brachytherapy today. A major change in brachytherapy, the development of high intensity sources, promoted clinical and technologic innovations in high dose-rate brachytherapy. Pulse dose-rate brachytherapy is the use of these sources to treat a target by using pulses of radiation for several minutes each hour with the same overall time and total dose as low dose-rate treatment. Recent novel approaches of using radiotherapy for prevention of restenosis in coronary and peripheral vessels has interested laboratory and clinical researchers. Most of the work toward new source material for brachytherapy centers around intravascular applications. Technology to support brachytherapy continues to advance rapidly. The interaction between images from diverse modalities and the various phases of the treatment planning is the basis of enhanced treatment planning procedures. Optimization in brachytherapy entails calculating the source strengths or source dwell times to satisfy a set of dose criteria to achieve the best dose distribution for a brachytherapy implant. Progress in computerization and calculation modeling has promoted this technical advance. Education and training in brachytherapy indications and techniques is mandatory to maintain high standards of brachytherapy practice.


[Role of A cells in the mitogenic stimulation of lymphocytes by Mycoplasma].
The dependence of the blast transformation of lymphocytes in response to phytohemagglutinin (PHA), concanavalin A (Con A) and Mycoplasma arthritidis on the concentration of A-cells and the time of the introduction of M. arthritidis into the culture was studied. The level of blast transformation in response to PHA, Con A and M. arthritidis increased with the decrease of the concentration of A-cells in the culture. After the combined inoculation of the culture with M. arthritidis and PHA the resulting effect was higher than that induced by PHA alone and lower than the level of blast transformation in response to M. arthritidis at all A-cell concentrations under study. After the combined inoculation of M. arthritidis and Con A the summation of response was observed in cultures with a high concentration of A-cells, while in cultures with a low concentration of A-cells the resulting response was lower than that induced by any of these mitogens alone. The inoculation of the culture with M. arthritidis 24-48 hours after the cultivation of splenocytes with PHA and Con A was started led to the suppression of response to the mitogens. The suppression of response to PHA was most pronounced at the maximum concentration of A-cells, while the suppression of response to Con A reached its highest level when the concentration of A-cells was low. These data are in accord with the suggestion that M. arthritidis and PHA, as well as M. arthritidis and Con A, stimulated the overlapping subpopulations of lymphocytes in rats, the adhesive properties being most pronounced in the subpopulation of PHA- and M. arthritidis-positive lymphocytes.


Evaluation of liquid media for growth of Helicobacter pylori.
Helicobacter pylori has routinely been isolated and grown on solid media. Recently, we have succeeded in obtaining growth of this organism in several liquid media in large volumes, including tryptic soy broth, Mueller-Hinton broth, brucella broth, brain heart infusion broth, and Columbia broth. Growth was tested in the media with and without supplementation. Growth was obtained after incubation under microaerobic conditions and with CO2 enrichment. Growth in a stationary system versus that in an agitated system was evaluated. Results from these experiments show that H. pylori can be grown in any of the liquid media tested except buffered yeast extract-alpha-ketoglutarate if serum is added. No growth was observed on buffered yeast extract-alpha-ketoglutarate even with serum and other supplementation. Growth of H. pylori in most of the liquid media with supplements was improved if the culture was incubated in a CO2 atmosphere. The findings reported here may be useful in clinical, industrial, and research laboratories that require harvests of large quantities of H. pylori cells.


The relationship between emotional intelligence and clinical teaching effectiveness in nursing faculty.
Nursing faculty play an important role in facilitating nursing student learning and shaping student experience in the clinical setting. Emotional intelligence (EI) in clinical nursing faculty may be one avenue to develop teaching effectiveness. This study investigated the relationship between EI and clinical teaching effectiveness of nursing faculty in an undergraduate nursing program. Using a cross-sectional correlation design, data were collected from a convenience sample of nursing faculty (N = 47) using the BarOn Emotional Quotient Inventory: Short (EQ-i:S), the Nursing Clinical Teacher Effectiveness Inventory (NCTEI) and a demographic data page. The results indicated a statistically significant positive relationship between the EQ-i:S and the NCTEI total scores (rs = .599, P < .01) and between many subscales of these tools. These findings contribute new knowledge to nursing education, including the following: (a) a significant relationship between EI and clinical teaching effectiveness exists, (b) faculty exhibit effective overall EI functioning with room to enhance competencies, and (c) faculty members see themselves as effective in their clinical teaching. Implications for clinical teaching practice include the need for faculty development and strengthening the faculty-student relationship. Possibilities for future research are discussed.


Respiratory Microbiota Profiles Associated With the Progression From Airway Inflammation to Remodeling in Mice With OVA-Induced Asthma.
The dysbiosis of respiratory microbiota plays an important role in asthma development. However, there is limited information on the changes in the respiratory microbiota and how these affect the host during the progression from acute allergic inflammation to airway remodeling in asthma. An ovalbumin (OVA)-induced mouse model of chronic asthma was established to explore the dynamic changes in the respiratory microbiota in the different stages of asthma and their association with chronic asthma progression. Hematoxylin and eosin (H&E), periodic acid-schiff (PAS), and Masson staining were performed to observe the pathological changes in the lung tissues of asthmatic mice. The respiratory microbiota was analyzed using 16S rRNA gene sequencing followed by taxonomical analysis. The cytokine levels in bronchoalveolar lavage fluid (BALF) specimens were measured. The matrix metallopeptidase 9 (MMP-9) and vascular endothelial growth factor (VEGF-A) expression levels in lung tissues were measured to detect airway remodeling in OVA-challenged mice. Acute allergic inflammation was the major manifestation at weeks 1 and 2 after OVA atomization stimulation, whereas at week 6 after the stimulation, airway remodeling was the most prominent observation. In the acute inflammatory stage, Pseudomonas was more abundant, whereas Staphylococcus and Cupriavidus were more abundant at the airway remodeling stage. The microbial compositions of the upper and lower respiratory tracts were similar. However, the dominant respiratory microbiota in the acute inflammatory and airway remodeling phases were different. Metagenomic functional prediction showed that the pathways significantly upregulated in the acute inflammatory phase and airway remodeling phase were different. The cytokine levels in BALF and the expression patterns of proteins associated with airway remodeling in the lung tissue were consistent with the metagenomic function results. The dynamic changes in respiratory microbiota are closely associated with the progression of chronic asthma. Metagenomic functional prediction indicated the changes associated with acute allergic inflammation and airway remodeling.