Pegfilgrastim +/- ciprofloxacin for primary prophylaxis with TAC (docetaxel/doxorubicin/cyclophosphamide) chemotherapy for breast cancer. Results from the GEPARTRIO study.
TAC (docetaxel/doxorubicin/cyclophosphamide) is associated with high incidences of grade 4 neutropenia and febrile neutropenia (FN). This analysis compared the efficacies of four regimens for primary prophylaxis of FN and related toxic effects in breast cancer patients receiving neoadjuvant TAC. Patients with stage T2-T4 primary breast cancer were scheduled to receive 6-8 cycles of TAC. Primary prophylaxis was: ciprofloxacin 500 mg orally twice daily on days 5-14 (n = 253 patients; 1478 cycles), daily granulocyte colony-stimulating factor (G-CSF) (filgrastim 5 microg/kg/day or lenograstim 150 microg/m(2)/day) on days 5-10 (n = 377; 2400 cycles), pegfilgrastim 6 mg on day 2 (n = 305; 1930 cycles), or pegfilgrastim plus ciprofloxacin (n = 321; 1890 cycles). Pegfilgrastim with/without ciprofloxacin was significantly more effective than daily G-CSF or ciprofloxacin in preventing FN (5% and 7% versus 18% and 22% of patients; all P < 0.001), grade 4 neutropenia, and leukopenia. Pegfilgrastim plus ciprofloxacin completely prevented first cycle FN (P < 0.01 versus pegfilgrastim alone) and fatal neutropenic events. Ciprofloxacin alone, or daily G-CSF from day 5-10 (as in common practice), provided suboptimal protection against FN and related toxic effects in patients receiving TAC. Pegfilgrastim was significantly more effective in this setting, especially if given with ciprofloxacin.


Quantum test of the equivalence principle for atoms in coherent superposition of internal energy states.
The Einstein equivalence principle (EEP) has a central role in the understanding of gravity and space-time. In its weak form, or weak equivalence principle (WEP), it directly implies equivalence between inertial and gravitational mass. Verifying this principle in a regime where the relevant properties of the test body must be described by quantum theory has profound implications. Here we report on a novel WEP test for atoms: a Bragg atom interferometer in a gravity gradiometer configuration compares the free fall of rubidium atoms prepared in two hyperfine states and in their coherent superposition. The use of the superposition state allows testing genuine quantum aspects of EEP with no classical analogue, which have remained completely unexplored so far. In addition, we measure the Eötvös ratio of atoms in two hyperfine levels with relative uncertainty in the low 10-9, improving previous results by almost two orders of magnitude.


Characterization of the porcine epidemic diarrhea virus codon usage bias.
Porcine epidemic diarrhea virus (PEDV) has been responsible for several recent outbreaks of porcine epidemic diarrhea (PED) and has caused great economic loss in the swine-raising industry. Considering the significance of PEDV, a systemic analysis was performed to study its codon usage patterns. The relative synonymous codon usage value of each codon revealed that codon usage bias exists and that PEDV tends to use codons that end in T. The mean ENC value of 47.91 indicates that the codon usage bias is low. However, we still wanted to identify the cause of this codon usage bias. A correlation analysis between the codon compositions (A3s, T3s, G3s, C3s, and GC3s), the ENC values, and the nucleotide contents (A%, T%, G%, C%, and GC%) indicated that mutational bias plays role in shaping the PEDV codon usage bias. This was further confirmed by a principal component analysis between the codon compositions and the axis values. Using the Gravy, Aroma, and CAI values, a role of natural selection in the PEDV codon usage pattern was also identified. Neutral analysis indicated that natural selection pressure plays a more important role than mutational bias in codon usage bias. Natural selection also plays an increasingly significant role during PEDV evolution. Additionally, gene function and geographic distribution also influence the codon usage bias to a degree.


Granulin-like peptide in the mid-gut gland of the bivalve mollusk, Patinopecten yessoensis.
A cysteine-rich polypeptide, termed CRP1, with a molecular mass of 5829 Da was found to occur in the mid-gut gland of the scallop Patinopecten yessoensis. CRP1 was purified by reverse phase and cation-exchange chromatographies. The amino acid sequence of CRP1 was deduced from its N-terminal amino acid sequence, amino acid composition and the sequence of a partial cDNA, indicating that CRP1 is a 57-amino-acid polypeptide containing 12 cysteine residues with a calculated molecular mass of 5841 Da (5829 Da when oxidized to form six disulfide bridges). A homology search of databases revealed that the deduced amino acid sequence of CRP1 displays significant similarity to those of granulin/epithelins, a family of growth-modulating factors; all cysteine residues in CRP1 are located at the same positions as those conserved characteristically in other known granulin/epithelins. Purified CRP1 inhibited the proliferation of mouse embryo cells. The results suggest that CRP1 functions as a growth-modulating factor in the scallop, and that granulin/epithelin family polypeptides and their precursors play physiologically important roles in invertebrates.


Mirtazapine use may increase the risk of hypothyroxinaemia in patients affected by major depressive disorder.
Hypothyroxinaemia could be easily neglected if attention is paid only to patients with elevated thyroid-stimulating hormone. We aimed to assess the association between mirtazapine use and hypothyroxinaemia in patients affected by major depressive disorder. We conducted a retrospective cohort study in the Second Affiliated Hospital of Xinxiang Medical University between January 2016 and December 2018. Patients affected by major depression disorder and admitted to the hospital for treatment during the study period and who had thyroid tests at admission and after treatment were included. Mirtazapine use during hospitalization was the exposure measure and newly developed hypothyroxinaemia was as the primary outcome and structure parameters of thyroid homeostasis were the secondary outcomes of this study. Log-binomial model was used to estimate the association between mirtazapine use and hypothyroxinaemia, after adjusting for potential confounding factors. A total of 220 eligible patients were included in the final analysis. The incidence of hypothyroxinaemia in patients who used mirtazapine was higher (37.5%) than those patients who did not use (19.7%). The relative risk of developing hypothyroxinaemia was 1.70 (95% confidence interval: 1.21-2.43) for mirtazapine use, after adjusting for confounding factors. The degree of reduction in thyroid feedback quantile-based index in mirtazapine group was significantly greater than that in nonmirtazapine group. Mirtazapine use was associated with the increased risk of developing hypothyroxinaemia. The underlying mechanism may be involved the changed central set point of thyroid homeostasis, in which pituitary was in a possibly impaired sensitivity to the lower level of thyroid hormones.


Preadolescents' Emotional and Prosocial Responses to Negative TV News: Investigating the Beneficial Effects of Constructive Reporting and Peer Discussion.
Watching news is important for preadolescents, but it may also harm their well-being. This study examined whether applying insights from positive psychology to news production can reduce this potential harm, by reducing negative emotional responses and enhancing positive emotional responses to negative news, and by encouraging prosocial intentions. Moreover, we explored whether peer discussion strengthened these effects. Preadolescents (n = 336; 9-13 years old; 48.5% female) were exposed to either constructive (solution-based news including positive emotions) or nonconstructive news. Subsequently, half of the children assigned to the constructive and the nonconstructive condition participated in a peer discussion. The findings showed that exposure to constructive news resulted in more positive emotional responses and less negative emotional responses as compared to nonconstructive news. Moreover, discussing the news with peers led to more positive and less negative emotional responses among preadolescents who watched the nonconstructive newscast, and to more prosocial intentions among preadolescents who watched constructive news. In all, constructive news reporting and peer discussion could function as tools to make negative news less harmful for preadolescents.


HIV-1 and breastfeeding: biology of transmission and advances in prevention.
Breastfeeding accounts for about 40% of mother-to-child transmission of HIV-1 worldwide and carries an estimated risk of transmission of 0.9% per month after the first month of breastfeeding. It is recommended that HIV-1-infected women completely avoid breastfeeding in settings where safe feeding alternatives exist. However, as replacement feeding is not safely available in many parts of the world, and because breastfeeding provides optimal nutrition and protection against other infant infections, there is intense ongoing research to make breastfeeding safe for HIV-1-infected mothers in resource-limited settings. More research is needed to determine the optimal duration of breastfeeding, optimal weaning practices, and which individual antiretroviral prophylactic regimen is best for HIV-1-infected mothers and their infants in a particular setting.


Restoration of ACTH/cortisol and LH responses to naloxone by chronic dopaminergic treatment in Parkinson's disease.
Naloxone is unable to stimulate ACTH/cortisol secretion in patients with de novo Parkinson's disease, suggesting a reduced endogenous opioid control of the hypothalamic-pituitary-adrenal axis in parkinsonian patients. In the present study we examined whether Parkinson's disease also impairs the secretion of LH, which is under the inhibitory control of different opioid peptides than ACTH/cortisol. In addition, we examined whether a chronic dopaminergic therapy for at least one year with levodopa (450 mg/day) plus benserazide (112.5 mg/day) in 3 divided oral doses/day of Madopar modifies the ACTH/cortisol and/or the LH response to naloxone (4 mg as an i.v. bolus plus 10 mg infused in 2 hours). Ten parkinsonian patients (aged 52-62 years) and 8 normal controls (50-60 years) were tested with naloxone and in a different occasion with normal saline. The parkinsonian patients were tested both before and after dopaminergic treatment. Tests started at 09.00 h and lasted 2.5 hours. Basal ACTH/cortisol and LH levels were similar in all groups. During saline tests, ACTH/cortisol levels showed a slight physiological decline in all groups, whereas LH levels remained constant. Naloxone administration significantly increased the plasma levels of ACTH/cortisol and LH in the normal controls, but not in the parkinsonian patients before the dopaminergic treatment. In contrast, dopaminergic therapy restored significant ACTH/cortisol and LH responses to naloxone in parkinsonian patients. In fact, after levodopa plus benserazide, naloxone-induced ACTH, cortisol and LH increments in parkinsonian patients were significantly higher than before therapy and were indistinguishable from those observed in the normal controls. These data suggest that in men Parkinson's-related dopaminergic alterations may underlie the defective endogenous opioid control of ACTH/cortisol and LH secretion.


Serotonergic modulation of the respiratory rhythm generator at birth: an in vitro study in the rat.
In order to investigate the mechanisms through which serotonin (5-HT) modulates the activity of the respiratory rhythm generator, respiratory activity was recorded from cervical ventral roots of the superfused isolated brainstem-spinal cord preparation of the newborn rat. Replacing the normal bathing medium by a medium containing 5-HT (30 microM) increased the respiratory frequency by 70% of the control value. Intact pontomedullary structures are necessary for this effect to take place, however, since the 5-HT-induced increases in respiratory frequency were no longer observed after elimination (section and electrolytic lesion) of the caudal ventro-lateral pons containing the A5 areas. Local applications of 5-HT (dual bath, microdialysis and microinjection experiments) revealed, however, that 5-HT acts at the medullary level and that its effects are not due to a diffuse action on all the neurons of the medullary respiratory centers but to a specific action focusing on structures located in the rostral ventro-lateral medulla.


The pregnancy-related anxiety characteristics in women with gestational diabetes mellitus: why should we care?
Gestational diabetes mellitus (GDM) is very commonly-seen in clinical settings, and GDM patients may have higher levels of anxiety. It's necessary to evaluate the anxiety level and potentially influencing factors in patients with GDM, to provide insights for the management of anxiety of GDM patients. Patients with GDM treated in our hospital from May, 2018 to May, 2020 were included. We evaluated the characteristics of patients and the scores of pregnancy-related anxiety scale for anxiety level, vulnerable personality style questionnaire (VPSQ) for personality, general self-efficacy scale (GSES) for self-efficacy, social support rating scale (SSRS) for social support level. Logistic regression analyses were conducted to identify the potential influencing factors of anxiety in GDM patients. A total of 386 GDM patients were included, the incidence of anxiety in patients with GDM was 59.07%. Anxiety was positively correlated with the susceptible personality (r = 0.604, p = 0.023), and it was negatively correlated with self-efficacy and social support (r = -0.586 and -0.598 respectively, all p < 0.05). The education level, monthly income, abnormal pregnancy (miscarriage, premature rupture of membranes) and cesarean section history and first pregnancy were the independent influencing factors for the anxiety in the patients with GDM (all p < 0.05). The anxiety of GDM patients is very common, early care and interventions are warranted for those patients with abnormal pregnancy and cesarean section history, first pregnancy, lower education level, and less monthly income.


Role of the ATPase/helicase maleless (MLE) in the assembly, targeting, spreading and function of the male-specific lethal (MSL) complex of Drosophila.
The male-specific lethal (MSL) complex of Drosophila remodels the chromatin of the X chromosome in males to enhance the level of transcription of most X-linked genes, and thereby achieve dosage compensation. The core complex consists of five proteins and one of two non-coding RNAs. One of the proteins, MOF (males absent on the first), is a histone acetyltransferase that specifically acetylates histone H4 at lysine 16. Another protein, maleless (MLE), is an ATP-dependent helicase with the ability to unwind DNA/RNA or RNA/RNA substrates in vitro. Recently, we showed that the ATPase activity of MLE is sufficient for the hypertranscription of genes adjacent to a high-affinity site by MSL complexes located at that site. The helicase activity is required for the spreading of the complex to the hundreds of positions along the X chromosome, where it is normally found. In this study, to further understand the role of MLE in the function of the MSL complex, we analyzed its relationship to the other complex components by creating a series of deletions or mutations in its putative functional domains, and testing their effect on the distribution and function of the complex in vivo. The presence of the RB2 RNA-binding domain is necessary for the association of the MSL3 protein with the other complex subunits. In its absence, the activity of the MOF subunit was compromised, and the complex failed to acetylate histone H4 at lysine 16. Deletion of the RB1 RNA-binding domain resulted in complexes that maintained substantial acetylation activity but failed to spread beyond the high-affinity sites. Flies bearing this mutation exhibited low levels of roX RNAs, indicating that these RNAs failed to associate with the proteins of the complex and were degraded, or that MLE contributes to their synthesis. Deletion of the glycine-rich C-terminal region, which contains a nuclear localization sequence, caused a substantial level of retention of the other MSL proteins in the cytoplasm. These data suggest that the MSL proteins assemble into complexes or subcomplexes before entering the nucleus. This study provides insights into the role that MLE plays in the function of the MSL complex through its association with roX RNAs and the other MSL subunits, and suggests a hypothesis to explain the role of MLE in the synthesis of these RNAs.


[Use of the computer in teaching rheumatology. Trial application in the diagnosis of an adult polyarthritis].
The immense possibilities offered by the computer can be utilized in medical education, through a free dialogue between the student and the machine thanks to a terminal. A diagnostic simulation program has been carried out in diagnosing adult polyarthritis. This program neccesitates an analysis of diagnostic behavior and, on this basis, the preparing of a diagnostic tree or graph. The reasons leading to the plan adopted in constructing the graph, are discussed. Cases of increasing difficulty are proposed to the student, who must follow the course plan in order to arrive at a diagnosis. This teaching method, applied for thing pedagogical advantages both for the teacher and the student. The operating cost seems reasonable.


Mupirocin for controlling methicillin-resistant Staphylococcus aureus: lessons from a decade of use at a university hospital.
From 1990 to 1995 at Hospital Universitário Clementino Fraga Filho, patients colonized or infected with methicillin-resistant Staphylococcus aureus (MRSA) were treated with mupirocin to eliminate MRSA carriage. In 1995, 65% of MRSA patients at this hospital had mupirocin-resistant isolates. Starting in 1996, mupirocin use was restricted to patients colonized, but not infected, with MRSA. To describe the use of mupirocin for controlling MRSA over a decade and to analyze the molecular epidemiology of mupirocin-resistant MRSA infections at this hospital. A 490-bed, tertiary-care university hospital. The incidence densities of patients with MRSA and acquisition of mupirocin by the hospital were calculated for the period 1992-2001. S. aureus isolates from 1999-2000 were analyzed by pulsed-field gel electrophoresis. Mupirocin-resistant MRSA isolates from 1994-1995 and 1999-2000 were analyzed for ileS-2 gene background polymorphisms. The incidence density of MRSA patients increased slightly over time, whereas the purchase of mupirocin decreased dramatically. Mupirocin-resistant MRSA infections decreased from 65% in 1994-1995 to 15% in 1999-2000. The MRSA Brazilian clone, detected in 1992, was still highly prevalent. The same ileS-2 encoding plasmid found in 1994-1995 persisted in three identical MRSA isolates from 1999-2000 belonging to the Brazilian clone. After mupirocin use decreased, the ileS-2 encoding plasmid persisted in only a few Brazilian clone isolates. Our data on mupirocin-resistant MRSA incidence and mupirocin use strongly suggested that restricted use was related to decreased rates of mupirocin resistance at our hospital.


Decreased functional connectivity in an executive control network is related to impaired executive function in Internet gaming disorder.
Resting brain spontaneous neural activities across cortical regions have been correlated with specific functional properties in psychiatric groups. Individuals with Internet gaming disorder (IGD) demonstrate impaired executive control. Thus, it is important to examine executive control networks (ECNs) during resting states and their relationships to executive control during task performance. Thirty-five IGD and 36 healthy control participants underwent a resting-state fMRI scan and performed a Stroop task inside and outside of the MRI scanner. Correlations between Stroop effect and functional connectivity among ECN regions of interest (ROIs) were calculated within and between groups. IGD subjects show lower functional connectivity in ECNs than do HC participants during resting state; functional-connectivity measures in ECNs were negatively correlated with Stroop effect and positively correlated with brain activations in executive-control regions across groups. Within groups, negative trends were found between Stroop effect and functional connectivity in ECNs in IGD and HC groups, separately; positive trends were found between functional connectivity in ECNs and brain activations in Stroop task in IGD and HC groups, separately. Higher functional connectivity in ECNs may underlie better executive control and may provide resilience with respect to IGD. Lower functional connectivity in ECNs may represent an important feature in understanding and treating IGD.


Free energy calculations of protein-ligand interactions.
In the calculation of free energies of binding for protein-ligand complexes, we distinguish endpoint methods, methods involving alchemical modifications and methods that physically displace the ligand from the protein. Most methodological advances seem to come from a clever combination of multiple existing methods to enhance the sampling or to utilize specific advantages of various approaches. The coupling parameters common in thermodynamic integration and in Hamiltonian replica exchange are for instance combined to yield replica exchange thermodynamic integration. As new methods mostly aim to improve efficiency or to attain more complete sampling, there are good prospects to understand and tackle the sampling problem better and to shift the focus towards the scoring problem in the context of more robust and accurate force fields.


[The problem of information value in microvascular networks].
The methodology of quantitative estimation of information value in microvascular networks is proposed for the first time with the use of wavelet analysis of skin blood flow oscillations registrated by laser Doppler flowmetry at 30 healthy persons and 56 patients after hand injuries and diseases. It includes calculation of relative indices for the information preservation, the predomination of preserved information and the efficacy of information. The most deviation from multistable information regimen happened after formation of resonance oscillations: the general quantity of information decreased but the preservation of predominated information increased. The preservation of trophic myogenic information predominated after reduction of sympathetic influences. With the increase in the number of information channels the quantity of information increased but its preservation varied. Sensory peptidergic nerve fibres were activated during local heating to 34 degrees C at dorsal forearm skin. This information was the most effective at the beginning of heating during the growth of blood flow to the plateau level. Blood flow oscillations represented in wavelet spectrum serve as operators build on the basis of effective information. These oscillations play not only hemodynamic role but are the bearers of information in microvascular networks.


[Arthroscopic capsular release of the elbow].
Limited mobility of the elbow joint can be due to various factors, the most common of which is trauma to the elbow. In addition, limited elbow movement can be a direct cause of decreased functionality and interfere with everyday life activities. The majority of the patients can recover a functional range of motion if physical therapy is combined with a splinting regimen. However, some patients will experience continued elbow stiffness. Traditionally, open techniques have been successful in releasing the elbow joint capsule and regaining functional range of motion. Early results of arthroscopic elbow capsule release were associated with an increased rate of peripheral nerve injury. Due to technical progress and modifications, arthroscopic capsular release of the elbow is now a safe and dependable--although technically challenging--method to regain elbow motion.


A predictive model for estimating the number of erythrocytapheresis or phlebotomy treatments for patients with naïve hereditary hemochromatosis.
Standard treatment for naïve hereditary hemochromatosis patients consists of phlebotomy or a personalized erythrocytapheresis. Erythrocytapheresis is more efficient, but infrequently used because of perceived costs and specialized equipment being needed. The main aim of our study was to develop a model that predicts the number of initial treatment procedures for both treatment methods. This information may help the clinician to select the optimal treatment modality for the individual patient. We analyzed retrospective data of 125 newly diagnosed patients (C282Y homozygous), treated either with phlebotomy (n = 54) or erythrocytapheresis (n = 71) until serum ferritin (SF) reached levels ≤100 μg/L. To estimate the required number of treatment procedures multiple linear regression analysis was used for each treatment method separately. The linear regression model with the best predictive quality (R2 = 0.74 and 0.73 for erythrocytapheresis and phlebotomy respectively) included initial SF, initial hemoglobin (Hb) level, age, and BMI, where initial SF was independently related to the total number of treatment procedures for both treatment methods. The prediction error expressed in RMSPE and RMSDR was lower for erythrocytapheresis than for phlebotomy (3.8 and 4.1 vs 7.0 and 8.0 respectively), CONCLUSIONS: Although the prediction error of the developed model was relatively large, the model may help the clinician to choose the most optimal treatment method for an individual patient. Generally erythrocytapheresis halves the number of treatment procedures for all patients, where the largest reduction (between 55% and 64%) is reached in patients with an initial Hb level ≥ 9 mmol/L (14.5 g/dL). ClinicalTrials.gov number NCT00202436.


Platelet 3H-imipramine binding in bipolar patients.
Platelet 3H-imipramine binding was investigated in 31 control subjects and 19 hospitalized bipolar patients, either in the hypomanic or the depressed phase of illness. The mean Bmax value in the bipolar depressed patients did not differ significantly from that in the control subjects or the hypomanic patients. Differences in timing of the assay after blood collection, membrane preparation, protein content used in the assay, or binding of radioactive ligand to the equipment do not appear to explain the discrepancy between these results and previous findings.


Single-particle properties of topological Wannier excitons in bismuth chalcogenide nanosheets.
We analyze the topology, dispersion, and optical selection rules of bulk Wannier excitons in nanosheets of Bi2Se3, a topological insulator in the family of the bismuth chalcogenides. Our main finding is that excitons also inherit the topology of the electronic bands, quantified by the skyrmion winding numbers of the constituent electron and hole pseudospins as a function of the total exciton momentum. The excitonic bands are found to be strongly indirect due to the band inversion of the underlying single-particle model. At zero total momentum, we predict that the s-wave and d-wave states of two exciton families are selectively bright under left- or right-circularly polarized light. We furthermore show that every s-wave exciton state consists of a quartet with a degenerate and quadratically dispersing nonchiral doublet, and a chiral doublet with one linearly dispersing mode as in transition metal dichalcogenides. Finally, we discuss the potential existence of topological edge states of chiral excitons arising from the bulk-boundary correspondence.


Cutaneous manifestation of IgG4-related disease mimicking dermatitis artefacta.
Dermatitis artefacta is a self-inflicted cutaneous disease presenting as sharply delineated ulcers, usually in accessible sites such as the head and neck. IgG4-related disease (IgG4-RD) is a recently recognised immune-mediated condition causing a fibroinflammatory process, resulting in the formation of tumefactive lesions in various organs, rarely presenting primarily in the skin. We report a case of cutaneous IgG4-RD clinically presenting as dermatitis artefacta.


Anaerobic degradation of digestate based hydrothermal carbonization products in a continuous hybrid fixed bed anaerobic filter.
This study investigates the suitability of continuous hybrid fixed bed anaerobic filter reactor for treating sewage and agro-industrial digestate hydrothermal carbonization (HTC) products; hydrochar and HTC liquor (HTCL). The reactor was operated for 300 days under mesophilic conditions at different organic loading rates (OLR); maximum OLRs of 7.4 and 10 gCOD/L/d were reached while treating HTC liquor and slurry, respectively. 15 g/L hydrochar were added to the reactor as a supplement while treating HTCL solely thus increasing the biogas production up to 153%. The reactor was fed with HTCL and hydrochar with an increasing mixing ratio, and the co-digestion impact was dependent on hydrochar concentrations. The results of the study indicate that the hybrid fixed bed anaerobic filter reactor is a promising anaerobic digestion configuration for treating HTCL and overcoming the HTC upscaling challenges, and the suitability of digestate hydrochar utilization as supplement material for anaerobic digestion.


T-lymphocytes regulate genetically determined airway hyperresponsiveness in mice.
Airway hyperresponsiveness (AHR) is a hallmark of asthma and a heritable polygenic trait in the mouse. In the mouse, candidate gene products of hematopoietic origin implicated in asthma mapped to the regions of the previously defined quantitative trait loci. Since hematopoietic cells have been implicated in the pathogenesis of asthma, we evaluated the role of hematopoietic cells in general and T cells specifically in the genetic modulation of native airway responsiveness in mice. Here, with the use of bone marrow transplantation, anti-T-cell monoclonal antibody treatment and T-cell transfer, we demonstrate that intrinsic non-atopic AHR is mediated by T lymphocytes. Our data support the novel concept that, in the absence of identified environmental influences, T cells enhance genetically determined airway responsiveness.


Intramembranous particle patches in myelin-deficient rat axons.
Focal accumulations of E-face intramembranous particles occur in spinal cord axons of myelin-deficient rat mutants. These resemble nodal particles and, like them, may represent voltage-sensitive sodium channels. It is proposed that axonal activity at these foci could increase extracellular potassium to the point of triggering activity in adjacent axons. Rapid spread of such potassium-induced activity among bare axons could underlie the seizures and other neurological abnormalities that develop in this mutant. A similar mechanism may account for the paroxysmal attacks sometimes seen in multiple sclerosis.


Instagram Sexualization: When posts make you feel dissatisfied and wanting to change your body.
Instagram is a visually centered social media that involves the presence of sexualized imagery posted by users. Such Instagram sexualization may have a negative impact on women's body image. The present study examined whether exposure to Instagram sexualization, namely posts of sexualized women along with appearance-related comments, affected women's body satisfaction and cosmetic surgery intentions. In doing so, it also considered the moderating role of Instagram Addiction Proclivity (IAP). Young Italian female participants (N = 247) were randomly exposed to one of four video conditions resulting from the combination of either sexualized or non-sexualized women's pictures on Instagram, paired with appearance or neutral comments. In the sexualized picture condition participants' body dissatisfaction increased compared to pre-exposure levels and to the non-sexualized picture condition. The type of comments did not affect participants' body satisfaction. Moreover, IAP predicted cosmetic surgery intentions and moderated their reactions to Instagram content. Indeed, the higher the IAP, the higher the cosmetic surgery intentions of participants viewing sexualized pictures with neutral comments and non-sexualized pictures with body appearance comments. These findings suggest that female Instagram users should be aware of the negative impacts of viewing sexualized imagery as well as the role that IAP may play.


Meet John Doe. When patients show up ahead of their paperwork, aggravation and unpaid bills usually follow.
Introducing your new patient. He's got insurance and an appointment, but Mr. Doe's paperwork is lost. Missing enrollment data on new patients is common. The bills frequently pile up--and some never get paid.


In vitro assessment of retinoic acid and aryl hydrocarbon receptor activity of treated effluent from 39 wastewater-treatment plants in Victoria, Australia.
This project involved the collection of final effluent samples from 39 wastewater-treatment plants (WWTPs) in Victoria, Australia, in late summer (late February to early March 2007). The 39 WWTPs included 15 lagoon-based plants and 24 with activated sludge-based processes. Samples were collected and subjected to measurement of retinoic acid receptor (RAR) and aryl hydrocarbon receptor (AhR) activity of the dissolved phase using yeast-based recombinant receptor-reporter gene bioassays. More than 90% of the effluents examined in this study elicited RAR activity (<0.5-198 ng/l a-t-RA equivalents [EQ]). All of the effluents had AhR activity (16-279 ng/l βNF EQ). Notwithstanding the paucity of comparative data, on the whole, the levels of RAR and AhR activity observed in this pilot survey of Victorian WWTP effluents were greater than those recently reported internationally. One assumption commonly made is that WWTP discharges will be diluted significantly in the receiving environment, further decreasing the potential risk of the discharges. Making this assumption may not be appropriate for some of Victoria's more ephemeral waterways or where effluent is discharged to an enclosed water body, such as a lake or terminal wetland. However, even where WWTP discharges represent all of the environmental flow in the warmer months, the observed RAR and AhR activity (as all-trans-retinoic acid (RA) and 2,3,7,8-tetrachloro-dibenzo-p-dioxin [TCDD] EQ, respectively) was still significantly lower than the concentrations of RA, and 2,3,7,8-TCCD known to cause developmental malformations in fish larvae after short-term exposure to these chemicals. Of perhaps greater concern, WWTP effluent can contain significant suspended solids (essentially biosolids), which may be a considerable sink for some hormonally active, hydrophobic compounds, and which may in turn increase the long-term exposure risk for aquatic fauna. Further studies of the nuclear and AhR activity of WWTP effluent suspended soilds are required to address this hypothesis.


HER2-positive metastatic, parotid salivary duct carcinoma treated with a trastuzumab/pertuzumab-based chemotherapy: A case report.
This case highlights the rare entity, salivary duct carcinoma (SDC), which is difficult to diagnose and manage. It is the first published case of a metastatic, HER2-positive parotid SDC successfully treated by a dual anti-HER2 treatment associated to a chemotherapy.


Muscle sympathetic nerve activity during wakefulness in heart failure patients with and without sleep apnea.
Sympathetic activation and sleep apnea are present in most patients with symptomatic systolic heart failure (HF). Acutely, obstructive and central apneas increase muscle sympathetic activity (MSNA) during sleep by eliciting recurrent hypoxia, hypercapnia, and arousal. In obstructive sleep apnea patients with normal systolic function, this increase persists after waking. Whether coexisting sleep apnea augments daytime MSNA in HF is unknown. We tested the hypothesis that its presence exerts additive effects on MSNA during wakefulness. Overnight sleep studies and morning MSNA recordings were performed on 60 subjects with ejection fraction <45%. Of these, 43 had an apnea-hypopnea index > or =15 per hour. Subjects with and subjects without sleep apnea were similar for age, ejection fraction, HF etiology, body mass index, blood pressure, and heart rate. Daytime MSNA was significantly higher in those with sleep apnea (76+/-2 versus 63+/-4 bursts per 100 heartbeats [mean+/-SEM], P=0.005; 58+/-2 versus 50+/-3 bursts/min, P=0.037), irrespective of its etiology (the mean difference for central sleep apnea was 17 bursts per 100 heartbeats; n=14; P=0.006; and for obstructive sleep apnea, 11 bursts per 100 heartbeats; n=29; P=0.032). In a subgroup (n=8), treatment of obstructive sleep apnea lowered MSNA by 12 bursts per 100 heartbeats (P=0.003). Convergence of independent excitatory influences of HF and sleep apnea on central sympathetic neurons results in higher MSNA during wakefulness in HF patients with coexisting sleep apnea. This additional stimulus to central sympathetic outflow may accelerate the progression of HF; its attenuation by treatment of sleep apnea represents a novel nonpharmacological opportunity.


The role of CYP2C19 in amitriptyline N-demethylation in Chinese subjects.
To determine the role of cytochrome P(450) (CYP)2C19 in N-demethylation of amitriptyline (AT) in healthy Chinese subjects. One hundred and one subjects were genotyped for CYP2C19 using polymerase chain reaction-restriction fragment length polymorphism analysis. Twelve unrelated adult men (19.7+/-0.6 years, 61.8+/-3.8 kg) were chosen and orally given a single dose of 50 mg AT, and the blood samples were drawn from a forearm vein at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, and 96 h after AT administration. Plasma concentrations of AT and nortriptyline (NT) were determined using high-performance liquid chromatography with an ultraviolet detector. The mean area under the plasma concentration-time curve (AUC(AT)) of CYP2C19 poor metabolizers (PMs, n=6) was significantly higher than that of CYP2C19 extensive metabolizers (EMs, n=6) (2207+/-501 ng/ml x h(-1) vs 1596+/-406 ng/ml x h(-1), P<0.05). In contrast, the mean AUC(NT(0-)(infinity)()) of PMs was significantly lower than that of EMs (294+/-70 ng/ml x h(-1) vs 684+/-130 ng/ml x h(-1), P<0.0001). Other pharmacokinetic parameters such as clearance, half-life, maximum plasma concentration, and time to peak plasma concentration showed no significant difference between PMs and EMs (0.41+/-0.12 l /h x kg(-1) vs 0.50+/-0.15 l /h x kg(-1), 25.0+/-6.2 h vs 24.1+/-4.4 h, 96+/-25 ng/ml vs 75+/-27 ng/ml, 4.0+/-1.4 h vs 3.7+/-1.5 h, respectively). The genetic defects of CYP2C19 have a significant effect on AT pharmacokinetics, and CYP2C19 plays an important role in N-demethylation of AT in vivo at a clinically therapeutic dose.


Bone Sclerostin and Dickkopf-related protein-1 are positively correlated with bone mineral density, bone microarchitecture, and bone strength in postmenopausal osteoporosis.
Wnt-catenin signaling antagonists sclerostin and dickkopf-related protein-1 (Dkk-1) inhibit bone formation and are involved in the pathogenesis of postmenopausal osteoporosis (PO). However, the association between sclerostin and Dkk-1 and bone mineral density (BMD) in women with PO remains unclear. This study aimed to determine the association between sclerostin and Dkk-1 and BMD, bone microarchitecture, and bone strength in PO. Trabecular bone specimens were obtained from the femoral heads of 76 Chinese women with PO who underwent hip arthroplasty for femoral neck fractures. Micro-computed tomography (Micro-CT) was used to assess the BMD and bone microarchitecture of the trabecular bone. Subsequently, a mechanical test was performed. Finally, sclerostin and Dkk-1 in the bone were measured by enzyme-linked immunosorbent (Elisa) assay. Serum ionized serum ionised calcium, propeptide of type 1 collagen, C-terminal β-telopeptide of type-1 collagen, sclerostin, and Dkk-1 were also detected. Bone sclerostin was positively correlated with serum ionised calcium, serum sclerostin, BMD, bone volume/tissue volume (BV/TV), trabecular number (Tb.N), maximum compressive force, and yield strength (r = 0.32, 0.906, 0.355, 0.401, 0.329, 0.355, and 0.293, respectively, P < 0.05) and negatively correlated with age and trabecular separation (Tb.Sp) (r = - 0.755 and - 0.503, respectively, P < 0.05). Bone Dkk-1 was positively correlated with serum ionised calcium, serum Dkk-1, BMD, BV/TV, trabecular thickness, Tb.N, maximum compressive force, yield strength, and Young's modulus (r = 0.38, 0.809, 0.293, 0.293, 0.228, 0.318, 0.352, 0.315, and 0.266, respectively, P < 0.05) and negatively correlated with age and Tb.Sp (r = - 0.56 and - 0.38, respectively, P < 0.05). Serum levels of sclerostin and Dkk-1 reflected the levels of sclerostin and Dkk-1 in the bone. Bone sclerostin and Dkk-1 were positively correlated with BMD in women with PO, and higher levels of bone sclerostin and Dkk-1 might predict better BMD, bone microarchitecture, and bone strength. The potential molecular mechanisms still require further study.


Pressure Ulcer in Trauma Patients: A Higher Spinal Cord Injury Level Leads to Higher Risk.
In a systematic review, the level of spinal cord injury (SCI) was not associated with risk for pressure ulcer (PU). We hypothesized that in the acute trauma population, upper-SCI (cervical/thoracic) has greater risk for PU when compared to lower-SCI (lumbar/sacral). We additionally sought to identify risk factors for development of PUs in trauma. A retrospective analysis of the NTDB (2007-2015) was performed. Covariates were included in a multivariable logistic regression analysis to determine risk for PU. Of 62,929 patients (0.9%) with SCI, most had an upper-SCI (83%). The overall rate of PUs in patients with SCI was 5.1%. More patients with upper-SCI developed PUs compared to lower-SCI (5.8% vs. 2.2%, p < 0.001). SCI was the strongest predictor for PU (OR = 13.77, CI = 13.25-14.31, p < 0.001). Upper-SCI demonstrated greater risk compared to lower-SCI (OR = 2.81, CI = 2.45-3.22, p < 0.001). Contrary to previous reports, a higher SCI level is associated with a three-fold greater risk for PU compared to lower SCI.


Intermolecular interactions in the crystal structures of potential HIV-1 integrase inhibitors.
2-[(2,5-dichloro-4-nitro-phenylamino)-methoxy-methyl]-8-hydroxy-quinoline 1 and 2-methyl-quinoline-5,8-dione-5-oxime 2 were obtained as potential HIV-1 integrase inhibitors and analyzed by X-ray crystallography. Semiempirical theoretical calculations of energy preferred conformations were also carried out. The crystal structures of both compounds are stabilized via hydrogen bonds and pi-pi stacking interactions. The planarity of compound 1 is caused by intramolecular hydrogen bonds.


BK virus infection in association with posttransplant urothelial carcinoma.
BK virus infection after transplantation is known to cause graft failure but the association with malignancies is controversial. BK virus workup was performed for kidney recipients in our center under conditions of hematuria or acute deterioration of graft function. We reviewed the history and reported our treatment and the disease course of three patients with BK virus later diagnosed with urothelial carcinoma. All three patients received kidneys from China with immunosuppression using a calcineurin inhibitor and monoclonal antibodies. Synchronous bladder and upper-tract tumors were treated with surgery followed by intravesical chemotherapies. We tapered the immunosuppressants and changed to a sirolimus-based regimen. Intravesical chemotherapy and concurrent chemoradiotherapy were performed to prevent recurrence. All three patients now have functional grafts. BK virus infection may lead to tumorigenesis. Besides decreasing immunosuppressants, we should be more alert to the detection of malignancies in BK virus-reactivated recipients. Early aggressive treatment may be curative, preserving functional grafts.


Natural history of occult hernias in adults at a safety-net hospital.
Occult hernias, hernias seen on radiologic imaging but not felt on physical exam, are common. Despite their high prevalence, little is known about the natural history of this finding. Our aim was to determine and report on the natural history of patients with occult hernias including the impact on abdominal wall quality of life (AW-QOL), need for surgery, and risk of acute incarceration/strangulation. This was a prospective cohort study of patients who underwent a computed tomography (CT) abdomen/pelvis scan from 2016 to 2018. Primary outcome was change in AW-QOL using the modified Activities Assessment Scale (mAAS), a hernia-specific, validated survey (1 = poor, 100 = perfect). Secondary outcomes included elective and emergent hernia repairs. A total of 131 (65.8%) patients with occult hernias completed follow-up with a median (IQR) of 15.4 (22.5) months. Nearly half of these patients (42.8%) experienced a decrease in their AW-QOL, 26.0% were unchanged, and 31.3% reported improvement. One-fourth of patients (27.5%) underwent abdominal surgery during the study period: 9.9% were abdominal procedures without hernia repair, 16.0% involved elective hernia repairs, and 1.5% were emergent hernia repairs. AW-QOL improved for patients who underwent hernia repair (+ 11.2 ± 39.7, p = 0.043) while those who did not undergo hernia repair experienced no change in AW-QOL (- 3.0 ± 35.1). When untreated, patients with occult hernias on average experience no change in their AW-QOL. However, many patients experience improvement in AW-QOL after hernia repair. Additionally, occult hernias have a small but real risk of incarceration requiring emergent repair. Further research is needed to develop tailored treatment strategies.


Port-wine-stain-associated dermatitis: implications for cutaneous vascular laser therapy.
Port-wine stains are congenital vascular malformations affecting 0.3% to 0.5% of infants. Dermatitis occurring exclusively or most severely within port-wine stains has been described in the literature. Traditionally, topical corticosteroid therapy has been used for the treatment of dermatitis, while pulseddye laser treatment is considered a safe and effective means of lightening the appearance of congenital port-wine stains. To describe the development of port-wine stain-associated dermatitis as well as a rational treatment approach to these patients, we studied three children with facial, limb, or truncal port-wine stains who developed dermatitis within the congenital vascular malformation either prior to or during treatment with pulseddye laser. Laser therapy of dermatitis-affected areas was subsequently deferred pending resolution of the dermatitis with topical corticosteroid or topical calcineurin inhibitor treatment. While pulseddye laser therapy is an effective means of lightening port-wine stains and achieving lasting resolution of any associated dermatitis, this therapy to dermatitis-affected areas should be postponed until the inflammation resolves to minimize the risk of laser-associated adverse effects.


Irritation from metalwork after ankle arthrodesis fixed using screws: a proportional meta-analysis and systematic review.
Ankle arthrodesis (AA) is often fixed using cannulated screws. The irritation from metalwork is a relatively common complication, but there is no consensus regarding the need to remove the screws on a systematic basis. The aim of this study was to determine (1) the proportion of screws removed after AA and (2) whether predictors of screw removal could be identified. This PRISMA-compliant systematic review was part of a larger previous protocol registered on the PROSPERO platform. Multiple databases were searched including studies in which patients undergone AA using screws as exclusive fixation method were followed. Data were harvested regarding the cohort, the study design, the surgical technique, the nonunion and complication rate at the longest follow-up. Risk of bias was assessed using the modified Coleman Methodology Score (mCMS). Forty-four series of patients from thirty-eight studies (1990 ankles, 1934 patients) were selected. The average follow-up was 40.8 months (range 12-110). In all studies, hardware was removed due to symptoms reported by patients and related to the screws. The pooled proportion of removal of metalwork was 3% (95% CI 2-4). The pooled proportion of fusion was 96% (95%CI 95-98), while the pooled proportion of complications and reoperations (excluding the removal of metalwork) stood at 15% (95% CI 11-18) and 3% (95% CI 2-4), respectively. The mean mCMS (50.8 ± 8.1, range 35-66) revealed only an overall fair quality of studies. The univariate analysis and the multivariate model showed that the year of publication (R = - 0.004; p = 0.01) and the number of screws (R = 0.08; p = 0.01) were associated with the screw removal rate. Specifically, we found that over time the removal rate decreased by 0.4% per year and that the use of three screws instead of two reduced the risk of removal of metalwork by 8%. In this review, removal of metalwork after ankle arthrodesis using cannulated screws was needed in 3% of cases at an average follow-up of 40.8 months. It was indicated only in case of symptoms related to soft tissue irritation from screws. The use of three screws was paradoxically related to a reduced risk of removal of screws as compared to two-screw constructs. Level IV, systematic review of Level IV.


Enhanced synthesis of the glucose/calcium-regulated proteins in a hamster cell mutant deficient in transfer of oligosaccharide core to polypeptides.
The properties of two Chinese hamster temperature-sensitive mutants, K12 and H3.5, were examined. Both mutants originated from the same parental cell line, Wg1A, and were isolated as cell cycle mutants arrested in G1. Previously, we had been shown that the H3.5 ts mutation affected the transfer of the oligosaccharide from the lipid carrier to the nascent polypeptide and that the K12 ts mutation regulated the transcription of two glucose/calcium-regulated genes. We report here that these two mutants exhibit almost identical phenotypes at the biochemical level. Furthermore, a genetic complementation test demonstrates that the two ts lesions must be closely related, or even identical. Our results suggest that a specific defect in glycosylation may result in the overproduction of the glucose/calcium-regulated proteins and is capable of activating the promoter of the major glucose-regulated gene.


Elution characteristics of residual monomers in different light- and auto-curing resins.
The aim of this in vitro study was to assess different auto-curing resins based on methylmethacrylate (MMA) and new light-curing resins based on urethane dimethacrylate (UDMA) regarding the residual monomers remaining in the resin and their elution over time. Specimens from three auto-curing and three light-curing resins were produced following the manufacturer's instructions. The concentration of residual MMA and UDMA monomers present in the resins as well as the quantity of the residual monomers released into artificial saliva solution after immersion times of 1, 3, and 7 days were analyzed by high-performance liquid chromatography (HPLC). Data were statistically analyzed using ANOVA and the post hoc Student-Newman-Keuls test. The highest and lowest amounts of residual monomers were found in the group of light-curing resins (p<0.05). The light-curing resins Triad Trans Sheet (0.06 wt%) and Primosplint (0.06 wt%) released over the entire immersion time of 7 days the smallest (p<0.05) quantity of UDMA. These two light-curing resins based on UDMA exhibited lower elution of residual monomers than auto-curing resins (MMA). The elution characteristics of the residual monomers do not seem to correlate with the residual monomer concentration in resins. These observations demonstrate that the quantitative determination of residual monomers alone - as required by the ISO specification 20795-1 - does not seem to be sufficient for an assessment of the biological properties of different resins. Instead, the evaluation of elution characteristics appears to be of higher clinical relevance.


Crystal structures of ethyl (2S*,2'R*)-1'-methyl-2'',3-dioxo-2,3-di-hydro-dispiro-[1-benzo-thio-phene-2,3'-pyrrolidine-2',3''-indoline]-4'-carboxyl-ate and ethyl (2S*,2'R*)-5''-chloro-1'-methyl-2'',3-dioxo-2,3-di-hydro-dispiro-[1-benzo-thio-phene-2,3'-pyrrolidine-2',3''-indoline]-4'-carboxyl-ate.
In the title compounds, C22H20N2O4S, (I), and C22H19ClN2O4S, (II), the pyrrolidine rings have twist conformations on the spiro-spiro C-C bonds. In (I), the five-membered ring of the oxindole moiety has an envelope conformation with the spiro C atom as the flap, while in (II) this ring is flat (r.m.s. deviation = 0.042 Å). The mean planes of the pyrrolidine rings are inclined to the mean planes of the indole units [r.m.s deviations = 0.073 and 0.069 Å for (I) and (II), respectively] and the benzo-thio-phene ring systems (r.m.s. deviations = 0.019 and 0.034 Å for (I) and (II), respectively) by 79.57 (8) and 88.61 (7)° for (I), and by 81.99 (10) and 88.79 (10)° for (II). In both compounds, the eth-oxy-carbonyl group occupies an equatorial position with an extended conformation. The overall conformation of the two mol-ecules differs in the angle of inclination of the indole unit with respect to the benzo-thio-phene ring system, with a dihedral angle between the planes of 71.59 (5) in (I) and 82.27 (7)° in (II). In the crystal of (I), mol-ecules are linked via pairs of N-H⋯O hydrogen bonds, forming inversion dimers enclosing R 2 (2)(14) loops. The dimers are linked via C-H⋯O and bifurcated C-H⋯O(O) hydrogen bonds, forming sheets lying parallel to (100). In the crystal of (II), mol-ecules are again linked via pairs of N-H⋯O hydrogen bonds, forming inversion dimers but enclosing smaller R 2 (2)(8) loops. Here, the dimers are linked by C-H⋯O hydrogen bonds, forming ribbons propagating along [010].


Measuring paediatric intensive care nursing knowledge in Australia and New Zealand: how the Basic Knowledge Assessment Tool for pediatric critical care nurses (PEDS-BKAT4) performs.
Validated professional knowledge measures are limited in paediatric intensive care unit (PICU) nursing. The Basic Knowledge Assessment Tool for Pediatric Critical Care Nurses (PEDS-BKAT4) measures knowledge, however content and practice differences exist between various PICUs. The study aim was to evaluate the PEDS-BKAT4 in the Australian and New Zealand setting. A panel of 10 experts examined item and scale content validity. Items were evaluated for 31 evidence-based item writing flaws and for cognitive level, by a 4-person expert panel. Thirty-six PICU nurses completed the PEDS-BKAT4, with reliability and item analysis conducted. Mean item content validity was 0.70, and 43% of items had content validity less than 0.8. Overall (Scale) content validity was 0.71. Thirty-five percent of items were classified as flawed. Thirty-five percent of items were written at the 'knowledge' level, and 58% at 'understanding'. The mean PEDS-BKAT4 score was 60.8 (SD=9.6), KR-20 reliability 0.81. The mean item difficulty was 0.62, and the mean discrimination index was 0.23. The PEDS-BKAT4 was not a reliable and valid measure of basic PICU nursing knowledge in Australian and New Zealand. Further research into the types of knowledge and skills required of PICU nurses in this setting are needed to inform the development of a future tool.


Successful engraftment of haploidentical stem cell transplant with post-transplantation cyclophosphamide in a patient with adenosine deaminase deficiency.
SCID are characterized by an imbalance in cellular and humoral immunity. Enzyme ADA deficiency represents from 10% to 15% of the SCID. This generates diminished maturation of the cell precursors. Treatments include enzyme replacement therapy, allogenic, or autologous HSCT with gene therapy, with HSCT being of choice when an identical HLA donor exists. Male patient, without relevant family antecedents or consanguinity. The patient had multiple infections during the first months of life, evidencing low immunoglobulin levels, with absence of T and B lymphocytes, and natural killer cells. Severe combined immunodeficiencies are considered due to ADA deficiency; management was begun and is derived to our hospital. Admission at 8 months of life, with chronic malnutrition and psychomotor retardation. The HLA studies were conducted without finding an identical donor, taken to HSCT with haploidentical donor. Conditioning regimen with cyclophosphamide, fludarabine, melphalan, and thymoglobulin. This patient received prophylaxis for graft-versus-host disease with cyclophosphamide, cyclosporine, and methotrexate. A 22 months post-transplant, the patient was without immunosuppressants or immunoglobulin, without evidence of graft-versus-host disease or new infections. The ADA deficiency is an infrequent pathology that can be potentially fatal if adequate treatment is not started. Haploidentical HSCT, using post-transplantation cyclophosphamide, emerges as a viable option with which good results can be achieved and improve the quality of life in patients with no other therapeutic alternatives.


Treatment of migraine headache after ocular surgery with intravenous metoclopramide hydrochloride.
To alert ophthalmologists that prolonged or severe postoperative periocular pain and nausea may be caused by migraine. We examined two patients who had a history of migraine and had severe episodes of prolonged periocular pain and nausea after ocular procedures. Both patients experienced symptoms similar to their previous migraine attacks. In neither was pain alleviated by routine analgesics. Each patient had relief of symptoms within two minutes after intravenous delivery of metoclopramide hydrochloride. Ophthalmologists should consider the diagnosis of postoperative migraine in similar patients and provide specific therapy such as intravenous metoclopramide hydrochloride.


The dosimetric effect of zipper artifacts on tomotherapy adaptive dose calculation--a phantom study.
Tomotherapy adaptive dose calculation offers the ability to verify and adjust the therapeutic plan during the treatment. Using tomotherapy adaptive dose calculation, the planned fluence pattern can be used to recalculate the dose distribution on pretreatment megavoltage computed tomography (MVCT) images. Zipper artifacts, which appear as increased density in the central region of MVCT images, may affect the accuracy of adaptive dose recalculation. The purpose of this study was to evaluate the dosimetric effects of zipper artifacts on tomotherapy adaptive dose calculation. MVCT images of a cylindrical water phantom of 22-cm diameter were acquired on a tomotherapy system. The zipper artifacts were enclosed by a cylindrical planning target volume (PTV) contoured on these images. For comparison, artifact-free images were created by replacing the computed tomography (CT) numbers of zipper artifacts with the mean CT number of water. Treatment plans were generated by giving a uniform dose of 2 Gy to the PTV based on these modified images; it was then applied to the images that have the zipper artifacts. The impacts of different pitch ratios on the artifacts were assessed. The dose distribution differences between the 2 sets of images were compared. The absorbed dose that covered 95% volume of PTV and maximum dose, minimum dose, and mean dose of the PTV were also calculated and compared. The water phantom was scanned on the tomotherapy system twice per week for 12 consecutive weeks. The mean CT number of zipper artifacts (101 HU) was three times higher than that of water (34 HU). The CT number value and location of zipper artifacts were not affected by the pitch ratio. Gamma analysis was performed between the original and recalculated dose distributions. The discrepancies between the isodose distributions calculated by two sets of images were within 1%/1-mm tolerance. The dosimetric impact from zipper artifacts was found insignificant such that the recalculated dose was underestimated by less than 0.5%.


The use of conventional and complementary therapies for insomnia among Hong Kong Chinese: a telephone survey.
To examine the prevalence and utilization pattern of complementary and alternative medicine (CAM) for insomnia in Hong Kong. Respondents were selected from the general population and interviewed by telephone Their sleep was assessed by a Chinese version of the Brief Insomnia Questionnaire (BIQ) and CAM use by a checklist. Prevalence findings were weighted by the BIQ insomnia diagnosis, age, and sex. 402 respondents completed the survey. The population-weighted prevalence of any treatment in the past 12 months was 21.3%, any CAM use at 12.3%, any conventional treatment at 6.5%, and alcohol use at 1.6%; however, 46.6% of the BIQ insomnia cases did not seek treatment. The most commonly used CAM modalities was Chinese herbal medicine (7.9%), followed by acupuncture (1.7%) and Western herbal products (1.7%). Most CAM therapies were used infrequently and without consultation of healthcare professionals. Only BIQ insomnia diagnosis and being female were found predictive of CAM use. Apart from Chinese herbal medicine and acupuncture, the use of conventional treatments, CAM, and alcohol for trouble sleeping was all less common in Hong Kong. Public education on the consequences of insomnia and various treatment modalities is needed.


A ketogenic diet protects DBA/1 and Scn1aR1407X/+ mice against seizure-induced respiratory arrest independent of ketosis.
Patients with uncontrolled epilepsy have a high risk of sudden unexpected death in epilepsy (SUDEP). Seizure-induced respiratory arrest (S-IRA) is thought to be the determining cause of death in many cases of SUDEP. The goal of the present study was to use Scn1aR1407X/+ (Dravet Syndrome, DS) and DBA/1 mice to determine: (1) the effect of a ketogenic diet (KD) on S-IRA and (2) the relationship between serum ketones and the protective effect of a KD. Ketogenic diet treatment significantly decreased spontaneous seizure-induced mortality in DS mice compared to control (8% vs 39%, p = 0.0021). This protective effect was not abolished when ketosis was prevented by supplementing the KD with glucose (10% mortality, p = 0.0007). In DBA/1 mice, the latency to onset of S-IRA due to audiogenic seizures was delayed from 7.6 to 20.8 seconds by a KD on treatment day (TD) 7 compared to control (p < 0.0001), an effect that was reversed on TD14 when mice were crossed over to a control diet on TD7. β-Hydroxybutyrate (BHB) levels were significantly decreased in DBA/1 mice on a KD supplemented with glucose (p = 0.0038), but the protective effect was maintained. Our findings show that a KD decreases SUDEP in DS mice and increases the latency to audiogenic S-IRA in DBA/1 mice. In both mouse models, a KD was protective against S-IRA. This effect may be due in part to specific dietary components rather than generation of ketone bodies.


Preparation of EDTA-modified magnetic attapulgite chitosan gel bead adsorbent for the removal of Cu(II), Pb(II), and Ni(II).
Attapulgite (ATP) has a unique porous layered chain structure and is an excellent environment-friendly decolorizer. However, its high viscosity makes it difficult to separate. First, it was combined with magnetic Fe3O4 nanoparticles to obtain Fe3O4-ATP that is easy to recycle and reuse. Then, Fe3O4-ATP nanoparticles were embedded in chitosan (CS) gel beads, and glutaraldehyde was used for cross-linking and curing. Lastly, ethylenediaminetetraacetic acid (EDTA) was successfully connected to Fe3O4-ATP/CS gel beads through amidation reaction, which further increased the capability of the adsorbent to adsorb heavy metal ions. The prepared magnetic composite adsorbent is a sphere with a rough surface and porous structure. The maximum adsorption capacity of the prepared Fe3O4-ATP/EDTA/CS adsorbent for Pb(II), Cu(II), and Ni(II) is 368.32, 267.94, and 220.31 mg g-1, respectively. After 5 times of repeated use, Fe3O4-ATP/EDTA/CS still showed good adsorption capacity for Cu(II), Pb(II), and Ni(II). Fe3O4-ATP/EDTA/CS has a large adsorption capacity for heavy metal ions, a wide pH applicability, good reuse, and rapid magnetic separation. In addition, Cu(II) loaded Fe3O4-ATP/EDTA/CS also showed good catalytic degradation performance for bisphenol A. This study prepared a new type of adsorbent with good adsorption performance and provided a promising method for the treatment of wastewater.


"Passive exercise" using whole body periodic acceleration: effects on coronary microcirculation.
The whole body periodic acceleration (WBPA) system has recently been developed as a "passive exercise" device by providing increased pulsatile shear stress for improvement of endothelial function. This study aimed to investigate the short-term effect of WBPA on coronary flow reserve (CFR) through transthoracic Doppler echocardiography (TTDE) in healthy subjects and patients with coronary artery disease (CAD). This study consisted of 15 healthy subjects and 20 patients with CAD who underwent CFR examination before and immediately after WBPA. The flow velocity in the distal portion of the left anterior descending coronary artery (LAD) was measured with TTDE at baseline and during adenosine infusion. Coronary flow reserve was calculated as the ratio of hyperemic to basal mean diastolic flow velocity. The WBPA treatment was completed in all 35 subjects without complications. There were no significant differences in heart rate and systolic blood pressure before and after WBPA. Whole body periodic acceleration increased CFR from 3.3 +/- 1.0 to 3.7 +/- 1.1 in the 35 subjects (P < .001). Coronary angiography showed significant LAD narrowing in 8 of the 20 CAD patients, but WBPA increased CFR from 2.4 +/- 0.4 to 2.7 +/- 0.5 in them as well (P < .01). This study demonstrates that WBPA improves CFR in healthy subjects and patients with CAD.


A follow-up study of patients with spinal cord injury in Sierra Leone.
Over an 18-month period, 24 patients were admitted with spinal cord injuries in a non-governmental organization hospital in one of the world's poorest countries, Sierra Leone. Seven patients died while in hospital. Follow-up data was available for 13 of the 17 survivors an average of 17.4 (10-28) months after discharge. Five patients were still alive.


A nanocellulose-based platform towards targeted chemo-photodynamic/photothermal cancer therapy.
Cellulose nanocrystals (CNCs) have advantages as drug delivery carriers because of their biocompatibility and the presence of hydroxyl groups which favor chemical modification and drug binding. The present study describes the development of novel multifunctional rod-like CNCs-based carriers as therapeutic platforms: CNCs were hybridized with folic acid for actively targeting tumor cells, carbon dots (Cdots) for both imaging and photodynamic/photothermal treatments and doxorubicin (DOX) as an anticancer drug. Hybridized carriers displayed excellent drug-loading capacity. Moreover, Cdots-containing hybrids showed fluorescence and photosensitized singlet oxygen generation and photothermal behavior. Carriers exhibited pH-sensitive drug release because of changing interactions with DOX, and this release proved to be effective against in vitro cervical cancer cells, as evidenced by dose-dependent reduced cellular viabilities. Additionally, DOX release was promoted by light irradiation and the photodynamic behavior by reactive oxygen species was confirmed. These results demonstrate the potential of multifunctional CNCs-based carriers as platforms for multimodal photodynamic/photothermal-chemotherapy.


Previous antibiotic exposure and antimicrobial resistance in invasive pneumococcal disease: results from prospective surveillance.
Estimating the risk of antibiotic resistance is important in selecting empiric antibiotics. We asked how the timing, number of courses, and duration of antibiotic therapy in the previous 3 months affected antibiotic resistance in isolates causing invasive pneumococcal disease (IPD). We conducted prospective surveillance for IPD in Toronto, Canada, from 2002 to 2011. Antimicrobial susceptibility was measured by broth microdilution. Clinical information, including prior antibiotic use, was collected by chart review and interview with patients and prescribers. Clinical information and antimicrobial susceptibility were available for 4062 (90%) episodes; 1193 (29%) of episodes were associated with receipt of 1782 antibiotic courses in the prior 3 months. Selection for antibiotic resistance was class specific. Time elapsed since most recent antibiotic was inversely associated with resistance (cephalosporins: adjusted odds ratio [OR] per day, 0.98; 95% confidence interval [CI], .96-1.00; P = .02; macrolides: OR, 0.98; 95% CI, .96-.99; P = .005; penicillins: OR [log(days)], 0.62; 95% CI, .44-.89; P = .009; fluoroquinolones: profile penalized-likelihood OR [log(days)], 0.62; 95% CI, .39-1.04; P = .07). Risk of resistance after exposure declined most rapidly for fluoroquinolones and penicillins and reached baseline in 2-3 months. The decline in resistance was slowest for macrolides, and in particular for azithromycin. There was no significant association between duration of therapy and resistance for any antibiotic class. Too few patients received multiple courses of the same antibiotic class to assess the significance of repeat courses. Time elapsed since last exposure to a class of antibiotics is the most important factor predicting antimicrobial resistance in pneumococci. The duration of effect is longer for macrolides than other classes.


Disruption of intestinal barrier and endotoxemia after traumatic brain injury: Implications for post-traumatic epilepsy.
Traumatic brain injury (TBI) may lead to the disruption of the intestinal barrier (IB), and to the escape of products of commensal gut bacteria, including lipopolysaccharide (LPS), into the bloodstream. We examined whether lateral fluid percussion injury (LFPI) and post-traumatic epilepsy (PTE) are associated with the increased intestinal permeability and endotoxemia, and whether these events in turn are associated with PTE. LFPI was delivered to adult male Sprague-Dawley rats. Before, 1 week, and 7 months after LFPI, the IB permeability was examined by measuring plasma concentration of fluorescein isothiocyanate-labeled dextran (FD4) upon its enteral administration. Plasma LPS concentration was measured in the same animals, using enzyme-linked immunosorbent assay. PTE was examined 7 months after LFPI, with use of video-EEG (electroencephalography) monitoring. One week after LFPI, the IB disruption was detected in 14 of 17 and endotoxemia - in 10 of 17 rats, with a strong positive correlation between FD4 and LPS levels, and between plasma levels of each of the analytes and the severity of neuromotor deficit. Seven months after LFPI, IB disruption was detected in 13 of 15 and endotoxemia in 8 of 15 rats, with a strong positive correlation between plasma levels of the two analytes. Five of 15 LFPI rats developed PTE. Plasma levels of both FD4 and LPS were significantly higher in animals with PTE than among the animals without PTE. The analysis of seven rats, which were examined repeatedly at 1 week and at 7 months, confirmed that late IB disruption and endotoxemia were not due to lingering of impairments occurring shortly after LFPI. LFPI leads to early and remote disruption of IB and a secondary endotoxemia. Early and late perturbations may occur in different subjects. Early changes reflect the severity of acute post-traumatic motor dysfunction, whereas late changes are associated with PTE.


First isolation and outbreak of OXA-48-producing Klebsiella pneumoniae in an Irish hospital, March to June 2011.
Five OXA-48-producing Klebsiella pneumoniae were detected in a tertiary referral hospital in Ireland between March and June 2011. They were found in the clinical isolates of five cases that were inpatients on general surgical wards. None of the cases had received healthcare at a facility outside of Ireland in the previous 12 months. This is the first report of OXA-48-producing K. pneumoniae in Ireland.


Effect of social distance on outcome evaluation in self-other decision-making: evidence from event-related potentials.
Previous studies have shown that social distance influences one's judgment at the decision-making stage, although its impact in the outcome evaluation stage, which is a vital stage in the decision-making process, is ignored. Using event-related potentials, we examined the influence of social distance on outcome feedback by requiring participants to make decisions for themselves, their friends, or strangers. Increased social distance reduced the feedback-related negativity amplitude in the early stage of outcome evaluation and reduced the P300 amplitude in the late stage of outcome evaluation. These results provide evidence for the power of social distance in decreasing motivation, emotional arousal, and cognitive investment in the outcome evaluation stage.


The fine structure of the embryonic envelopes before and after hatching in bothriocephalids: physiological and ecological significance.
The fine structure and differentiation of the embryonic envelopes before and after hatching in two bothriocephalid species of teleostean fish are described. Scanning electron microscopic observation of the egg surface confirmed the specific ornamentation of the capsule. Its thickness and topographic morphology reflect the physiocochemical characteristics of the environment. Beneath the eggshell, two syncytial layers were observed around the oncosphere. The outer envelope, visible during the preoncospheral phase, degenerated before the liberation of the coracidium. Glycoconjugate labelling confirmed the nutritive character of this layer. After hatching, the inner envelope was the only layer covering the oncosphere. The apical plasma membrane of the coracidial sheath bore cilia and numerous clublike microvilli. Beneath the cortical zone, the syncytial cytoplasm was vacuolated, resembling a honeycomb; the electron-dense zone, described from other pseudophyllideans, was not present. The basal membrane of the inner envelope, uniformly electron-dense, was assimilated by the oncospheral membrane. Comparison of the composition of the embryonic envelopes of pseudophyllideans with those of other tapeworm orders and trematodes revealed ontogenetic, structural and functional similarities between the embryotrophic layers. The physiological and ecological significance of the structure of the free-swimming coracidium is discussed. In this respect, the inner envelope around the oncosphere appears to be responsible for the inability of the larva to detect and invade the intermediate host.


[The present status of blood filtration--fundamentals and the clinical significance of leukocyte depletion and microaggregate filters in blood transfusion].
In this review the role of the latest generation of leukodepletion blood filters and the adverse reaction of leukocytes i.e. alloimmunisation, immunosuppression, nonhaemolytic febrile transfusion reaction, platelet refractoriness, transmission of infectious agents are described and discussed. Leukocyte-poor blood component is indicated for patients with a history of nonhaemolytic febrile transfusion reaction, in avoiding alloimmunisation in patients waiting for transplantation or platelet refractoriness and in preventing CMV-infection. In the review the role of microaggregate filters in transfusion complications, namely, nonhaemolytic febrile transfusion reaction, thrombocytopenia, adult respiratory distress syndrome (ARDS), fibronectin depletion and histamine release is evaluated. The need of microfiltration of autologous blood is discussed. It appears that the use of 40 microns microfilters is warranted in a broad array of intensive care settings.


Public contestation over agricultural pollution: a discourse network analysis on narrative strategies in the policy process.
The overuse of fertilizers in agriculture and their entry into freshwater has many negative impacts on biodiversity and poses problems for drinking water resources in Germany. In response to exceeding levels of nitrate concentrations in groundwater in parts of the country, an intense public dispute evolved and a significant policy change in fertilizer regulation occurred in 2020. Based on the German case of agricultural water pollution, this study demonstrates in an innovative way how discourse network analysis is a fruitful method for the integrated study of actor coalitions and their use of narrative strategies in public debate. Theoretically, the study draws on the narrative policy framework (NPF) to explain how actor coalitions use narrative strategies to attempt to influence policymaking on water pollution by agricultural activities. The empirical analysis builds on newspaper articles and press releases disseminated between 2010 and 2020. The results demonstrate how two opposing actor coalitions with congruent policy beliefs formed in the struggle over fertilizer regulation. These not only diverged in their policy beliefs but also differed in their use of narrative strategies to try to expand or contain the policy issue. More precisely, the coalitions adapted their narratives over time in response to changes in the likelihood to win or lose. Furthermore, the results suggest the coalition in favor of stricter fertilizer regulation was more sophisticated in its effort to mobilize specific target groups. Overall, the article provides a valuable contribution to the literature on the NPF by combining research on coalition formation and policy narratives. The online version contains supplementary material available at 10.1007/s11077-021-09439-x.


Symptoms and Impacts in Non-Metastatic Castration-Resistant Prostate Cancer: Qualitative Study Findings.
We developed a conceptual model to define key concepts associated with patients' experiences with the signs, symptoms, and impacts of non-metastatic castration-resistant prostate cancer (M0-CRPC). A targeted review of peer-reviewed literature, and other publicly available information, identified and categorized symptoms and impacts related to early-stage prostate cancer. Semi-structured interviews with five clinical experts helped determine the most relevant and important concepts for patients with M0-CRPC. Qualitative interviews with 17 patients with M0-CRPC identified the most frequently experienced symptoms and impacts, and their degree of interference with patients' lives. The findings from these three lines of evidence were summarized in a conceptual model. Literature searches identified mainly urinary, intestinal, and sexual symptoms. Experts noted the symptoms most frequently mentioned by patients include erectile dysfunction, loss of sexual desire or interest, incontinence/leaking, urgency, and hot flashes. Patient interviews confirmed the high frequency of erectile dysfunction, loss of libido, urinary urgency, and incontinence. The most frequently mentioned impacts expressed by patients were the need to monitor/plan for urinary frequency, interference with/restriction of daily activities, and frustration or anxiety over diagnosis, symptoms, or treatment. Symptoms and impacts most frequently experienced by patients were typically not those with the greatest effects on their lives; rather, those with the greatest consequences were related to treatment. The leading concerns associated with M0-CRPC were related to voiding and sexual dysfunction. The most relevant symptoms and impacts expressed by patients may be a consequence of therapy rather than of the disease.


Long-term effect of metformin on blood glucose control in non-obese patients with type 2 diabetes mellitus.
We aimed to investigate the long-term effect of metformin on the blood glucose control in non-obese patients with type 2 diabetes mellitus. A retrospective study was performed in 213 patients with type 2 diabetes mellitus under the administration of metformin for more than one year. The clinical parameters were investigated for 3 years. The obese and non-obese individuals were defined as a body mass index (BMI) of 25 kg/m2 or over (n = 105) and a BMI of less than 25 kg/m2 (n = 108), respectively. HbA1c levels were significantly decreased compared with those at the baseline time. The course of HbA1c was similar between the non-obese and the obese groups, while the dose of metformin required to control blood glucose was significantly lower in the non-obese group than in the obese group. The reductions in HbA1c were 1.2% and 1.1% at 12 months, 0.9% and 0.9% at 24 months, and 0.8% and 1.0% at 36 months in the non-obese and obese groups, respectively. BMI did not change during the observation periods. Approximately half of all patients required no additional antidiabetic agents or a reduction in other treatments after the initiation of metformin in either of the two groups. The present study demonstrated the long-term beneficial effect of metformin in non-obese (BMI < 25 kg/m2) diabetic patients. This effect appears to be maintained even after the observation period of this study, because metformin was limited to a relatively low dose in the non-obese group and the observed worsening in glycemic control over time can probably be attenuated by increasing the dose of metformin.


Test-retest reliability and reproducibility of long-label pseudo-continuous arterial spin labeling.
Arterial spin labeling MRI can quantify the cerebral blood flow (CBF) without exogenous tracer. However, the variation of arterial transit time across different brain regions introduces bias for measuring local CBF, especially for those subjects with long arterial transit time (ATT). Long post-labeling delay (PLD) or multi-PLD methods could mitigate the problem of heterogenous ATT at the expense of the signal-to-noise ratio (SNR). Long-label ASL might address the low SNR problem by increasing the amount of labeled arterial blood. Thus, we hypothesized that with the same relatively long PLD, long-label pCASL may be more robust and reproducible than standard-label pCASL in population with potentially prolonged ATT. The purpose of the study was to investigate the reliability and reproducibility of long-label pCASL in the whole brain and vascular regions of interest in an elderly population, compared with standard-label pCASL. Twenty adult volunteers (14 males, 6 females; age, 56.6 ± 17.2 years) were scanned twice on one 3.0 T scanner by standard-label pCASL (label duration (LD) = 1500 ms, PLD = 2000 ms) and long-label pCASL (LD = 3500 ms, PLD = 2000 ms). The intraclass correlation coefficient (ICC), within-subject coefficient of variation (wsCV), random noise and signal coefficient of variation(CoV) were used to assess global and regional reliability and reproducibility. Measurement agreement and difference were compared in different brain regions using correlation coefficient plots and Bland-Altman plots respectively. CBF value measured by long-label pCASL was overall higher than standard-label pCASL in all ROIs. Long-label pCASL had higher ICC than standard-label pCASL in most ROIs, and lower wsCV, random noise and CoV in all ROIs. Regardless of ASL method used, anterior circulation flow territories (ICC, 0.93-0.97; wsCV, 0.03-0.06) had higher CBF reliability and reproducibility than posterior circulation flow territories (ICC, 0.89; wsCV, 0.06-0.08). In all ROIs, the correlation analysis showed higher test-retest agreement (rlong-label > rstandard-label) and the Bland-Altman plots demonstrated lower measurement difference in long-label pCASL. The study demonstrated good reliability and reproducibility of long-label pCASL in anterior brain regions in the elderly population. To further improve CBF quantification in a long-ATT population while proper PLD is already used, increasing the label duration may help.


Three-dimensional mapping of brain venous oxygenation using R2* oximetry.
Cerebral venous oxygenation (Yv ) is an important biomarker for brain diseases. This study aims to develop an R2*-based MR oximetry that can measure cerebral Yv in 3D. This technique separates blood signal from tissue by velocity-encoding phase contrast and measures the R2* of pure blood by multi-gradient-echo acquisition. The blood R2* was converted to Yv using an R2*-versus-oxygenation (Y) calibration curve, which was obtained by in vitro bovine blood experiments. Reproducibility, sensitivity, validity, and resolution dependence of the technique were evaluated. In vitro R2*-Y calibration plot revealed a strong dependence of blood R2* on oxygenation, with additional dependence on hematocrit. In vivo results demonstrated that the technique can provide a 3D venous oxygenation map that depicts both large sinuses and smaller cortical veins, with venous oxygenation ranging from 57 to 72%. Intrasession coefficient of variation of the measurement was 3.0%. The technique detected an average Yv increase of 10.8% as a result of hyperoxia, which was validated by global oxygenation measurement from T2 -Relaxation-Under-Spin-Tagging (TRUST) MRI. Two spatial resolutions, one with an isotropic voxel dimension and the other with a nonisotropic dimension, were tested for full brain coverage. This study demonstrated the feasibility of 3D brain oxygenation mapping without using contrast agent. Magn Reson Med 79:1304-1313, 2018. © 2017 International Society for Magnetic Resonance in Medicine.


LncRNA CANT1 suppresses retinoblastoma progression by repellinghistone methyltransferase in PI3Kγ promoter.
Retinoblastoma (RB) is the most common malignant intraocular tumor of childhood. Recent studies have shown that long noncoding RNAs (lncRNAs), which are longer than 200 bp and without protein-coding ability, are key regulators of tumorigenesis. However, the role of lncRNAs in retinoblastoma remains to be elucidated. In this study, we found that the expression of lncRNA CASC15-New-Transcript 1 (CANT1) was significantly downregulated in RB. Notably, overexpression of CANT1 significantly inhibited RB growth both in vitro and in vivo. Furthermore, lncRNA CANT1, which was mainly located in the nucleus, occupied the promoter of phosphoinositide 3-kinase gamma (PI3Kγ) and blocked histone methyltransferase hSET1 from binding to the PI3Kγ promoter, thus abolishing hSET1-mediated histone H3K4 trimethylation of the PI3Kγ promoter and inhibiting PI3Kγ expression. Furthermore, we found that silencing PI3Kγ either by lncRNA CANT1 overexpression or by PI3Kγ siRNA, reduced the activity of PI3K/Akt signaling and suppressed RB tumorigenesis. In summary, lncRNA CANT1 acts as a suppressor of RB progression by blocking gene-specific histone methyltransferase recruitment. These findings outline a new CANT1 modulation mechanism and provide an alternative option for the RB treatment.


The importance of diversity and outreach in geroscience research: Insights from the Annual Biomedical Research Conference for Minority Students.
US academic science lacks racial, ethnic, sex, gender, disability, and socioeconomic diversity. Addressing this problem is essential to drive scientific progress but is confounded by broad misunderstandings regarding diverse groups. Increasing representation in science is particularly relevant in geroscience, where our research to maximize healthy human lifespan must also address existing racial and socioeconomic health disparities. The American Aging Association (AGE) is committed to addressing these issues as part of its larger mission to advance and promote geroscience research. Over the last three years, AGE has sponsored an exhibition booth staffed by trainee leaders to promote our society and research at the Annual Biomedical Research Conference for Minority Students (ABRCMS), an ideal venue to interact with diverse students from across the country. Through our interactions with students, advocates, and representatives from other institutions and societies, we have learned a great deal about how to engage and promote the success of diverse students in the sciences. Here, we share these insights that are helping shape our own outreach efforts. In addition to interacting with ABRCMS attendees, we also learned a great deal about how societies like AGE can partner with other organizations to advance our shared goals and the importance of reaching students early in their academic journey to promote their success. Finally, we consider how to grow our outreach efforts beyond ABRCMS to reach those in disadvantaged areas and support students navigating academic science.


The Role of Free Radical Oxidation in the Development of Experimental Urate Nephropathy.
We studied the dynamics of activity of antioxidant enzymes under conditions of experimental urate kidney damage in rats. Combined administration of uric (0.145 g) and oxonium (0.3 g) acids to laboratory animals modulated free radical oxidation in the kidneys, and especially, in the blood. During the week 1, activity of free radical processes decreased, which was probably determined by the antioxidant effect of increasing blood concentration of uric acid. After 2-3 weeks of experimental pathology, the development of oxidative stress was observed, probably due to predominance of prooxidant activity of uric acid.


Oxidative formation of bis-N-methylquinolinone from anti-head-to-head N-methylquinolinone cyclodimer.
The light-driven formation and cleavage of cyclobutane structural motifs resulting from [2 + 2]-pericyclic reactions, as found in thymine and coumarin-type systems, is an important and intensively studied photochemical reaction. Various applications are reported utilizing these systems, among others, in cross-linked polymers, light-triggered drug release, or other technical applications. Herein coumarin is most frequently used as the photoactive group. Quite often, a poor quantum yield for dimerization and cyclobutane-cleavage and a lack of reversibility are described. In this work, we present the identification of a heterogeneous pathway of dimer cleavage found in a rarely studied coumarin analog molecule, the N-methyl-quinolinone (NMQ). The monomer was irradiated in a tube flow-reactor and the reaction process was monitored using online HPLC measurements. We found the formation of a pseudo-equilibrium between monomeric and dimeric NMQ and a continuous rise of a side product via oxidative dimer splitting and proton elimination which was identified as 3,3'-bis-NMQ. Oxidative conversion by singlet oxygen was identified to be the cause of this non-conventional cyclobutane cleavage. The addition of antioxidants suppressing singlet oxygen enables achieving a 100% photochemical conversion from NMQ to the anti-head-to-head-NMQ-dimer. Using dissolved oxygen upon light activation to singlet oxygen limits the reversibility of the photochemical [2 + 2]-cycloaddition and cycloreversion of NMQ and most likely comparable systems. Based on these findings, the development of highly efficient cycloaddition-cycloreversion systems should be enabled.


Anterior (dorsal) paraclinoid aneurysm: case report.
Saccular aneurysms arising at locations other than arterial divisions have been reported but are extremely rare. Such a case of a previously unclassified paraclinoid aneurysms that arose from the anterior (dorsal) wall of the proximal internal carotid artery is reported. The neck of this aneurysm was located distal to the junction of the ophthalmic artery, which originated in the cavernous sinus. I propose that this aneurysm be classified as an anterior (dorsal) paraclinoid aneurysm.


Vaccination in neuromyelitis optica spectrum disorders: Friend or enemy?
Neuromyelitis optica spectrum disorders (NMOSDs) are uncommon antibody-mediated autoimmune diseases of the central nervous system (CNS), mainly occurring in optic nerves and spinal cord, which can cause visual impairment, paralysis, and occasionally bulbar dysfunction. Such neurological deficits can adversely affect pulmonary functions and increase complicated infection risk. Besides, most NMOSD patients undergo immunosuppressive therapy. All these factors make NMOSD patients the potential high-risk group under the current pandemic of coronavirus disease 2019 (COVID-19). Meanwhile, COVID-19 infection has already been demonstrated as a risk factor for NMOSD relapses. This review discusses the basic immunology of vaccination and common problems, including immunogenicity, safety, and efficacy of vaccination on NMOSD patients. Additionally, we offered vaccination recommendations, health care and treatment advice for NMOSD patients under the background of COVID-19.


Diverse ring-opening reactions of rhodium η4-azaborete complexes.
Sequential treatment of [Rh(COE)2Cl]2 (COE = cyclooctene) with PiPr3, alkyne derivatives and t BuN[triple bond, length as m-dash]BMes (Mes = 2,4,6-trimethylphenyl) provided functionalized rhodium η4-1,2-azaborete complexes of the form (η4-azaborete)RhCl(PiPr3). The scope of this reaction was expanded to encompass alkynes with hydrogen, alkyl, aryl, ferrocenyl, alkynyl, azaborinyl and boronate ester substituents. Treatment of these complexes with PMe3 led to insertion of the rhodium atom into the B-C bond of the BNC2 ring, forming 1-rhoda-3,2-azaboroles. Addition of N-heterocyclic carbenes to azaborete complexes led to highly unusual rearrangements to rhodium η2,κ1-allenylborylamino complexes via deprotonation and C-N bond cleavage. Heating and photolysis of an azaborete complex also led to rupture of the C-N bond followed by subsequent rearrangements, yielding an η4-aminoborylallene complex and two isomeric η4-butadiene complexes.


Acute tolerance to amphetamine in rats.
Two groups of rats were given amphetamine intravenously at 5-min intervals (5 or 10 mg/kg/h) for 8 h. Two control groups received saline infusions. On the second day a test dose of 10 mg/kg amphetamine was given to all groups. Body temperature, food intake, and motor behavior were registered every 30 or 60 min. The results showed the development of acute tolerance to the hyperthermic effect within 3-5 h. Tolerance was still visible on the 2nd day. There was also tolerance to the anorectic effect, which was evident on the 2nd day. One element of stereotyped behavior (swaying) also decreased during the amphetamine infusions.


Cognitive function assessed by Mini-mental state examination and risk of all-cause mortality: a community-based prospective cohort study.
The Mini-Mental State Examination (MMSE) is the most widely used instrument to test cognitive functioning. The present study prospectively investigated the association between MMSE scores, MMSE domains, and all-cause mortality. A total of 2134 participants aged 60 years or over, selected from one urban community-dwelling population in China, were enrolled in the study. The cognitive test was performed by use of the MMSE at baseline, and covariates were recorded simultaneously. Cox regression models were used for examining the cognitive function, expressed by different MMSE transformations, and all-cause mortality. After followed up for a median of 10.8 years (ranging from 1.0 to 11.3 years), loss to follow-up was 13.1% and 1854 individuals were finally included in the analyses. The subjects had the mean (SD) age of 71.01 (7.00) years, and 754 (40.67%) of them were women. Per point increase on MMSE scores was associated a 4% decreased risk of all-cause mortality [hazard ratio (HR): 0.96; 95%confidence interval (CI): 0.93-0.98]; compared to MMSE scores of ≥24, MMSE scores of < 24 was associated with a 43% increased risk of all-cause mortality (HR: 1.43; 95% CI: 1.05-1.95); compared to MMSE scores of 30, MMSE scores of 27-29 (HR: 1.27; 95% CI: 0.89-1.82), 24-26 (HR: 1.30; 95% CI: 0.86-1.99), and < 24 (HR: 1.79; 95% CI: 1.15-2.77) had a graded increase in risk of all-cause mortality (p for trend =0.003). Of MMSE domains, orientation to time (HR: 2.00; 95% CI: 1.29-3.11), attention and calculation (HR: 1.49; 95% CI: 1.16-1.92), recall (HR: 2.59; 95% CI: 1.22-5.47), and language (HR: 1.68; 95% CI: 1.25-2.26) were significantly associated with all-cause mortality in the unadjusted model; for one increase in the number of impaired MMSE domains, the unadjusted HR (95% CI) of mortality is 1.51 (1.38, 1.65), and the HR (95% CI) of mortality is 1.12 (1.01, 1.25) with full adjustment; compared to 0 and 1 impaired MMSE domains, the HRs of all-cause mortality associated with 2, 3, 4, and ≥ 5 impaired MMSE domains were 1.14 (95% CI: 0.84-1.54), 1.50 (95% CI: 0.98-2.28), 2.14 (95% CI: 1.12-4.09) and 2.29 (95% CI: 1.24-5.04), respectively, and a dose-dependent relationship was significant (p for trend =0.003). Cognitive impairment is associated with the increased risk of all-cause mortality in the Chinese elderly. Similarly, reduced MMSE scores, as well as impaired MMSE domains, are also associated with the increasing risk of all-cause mortality.


THE POSSIBILITIES OF CONE-BEAM COMPUTER TOMOGRAPHY IN THE DIAGNOSTIC OF FRACTURES OF THE MANDIBLE WITHIN THE DENTAL ROW.
The aim: To establish the possibilities and advantages of cone-beam tomography in the primary diagnostic of mandibular fractures within the dental row compared with traditional methods of radiation diagnosis. Materials and methods: The research was performed involving of 28 patients who had traumatic injuries of the maxillofacial area. The age of the victims was 18-56 years. The injured people were selected who were examinated by traditional radiological methods of diagnosis in the first hours after injury, and for final diagnostic in hospital were used cone-beam tomography of the mandible. The comparison of the results obtained with the help of traditional X-ray examinations with the data of cone-beam tomography allowed to conduct a comparative analysis of the diagnostic capabilities of these methods and to determine the advantage of the last one. Results: A comparative analysis of the results of the examination of injured people, which were obtained by using of traditional methods and cone-beam tomography of the mandible, shows the diagnostic advantages of the last one, which allows to determine the extent of traumatic injuries of the mandible and identify hidden fractures that were not determined by traditional X-ray methods. Conclusions: For the primary diagnostics of traumatic mandibular injuries, traditional X-ray examinations may be informative, but for complex, combined injuries, as well as fractures that raise doubts,it is advisable to use cone-beam computed tomography. The use of cone-beam computed tomography in mandibular fractures makes it possible to better assess the degree of damage and determine the displacement of fragments.