Retrospective, longitudinal, and cross sectional study of visual acuity impairment in choroideraemia.
Few studies have reported on the change in visual acuity (VA) in patients with choroideraemia. In order to determine the degree and rate of VA impairment associated with this disease, the central VA was analysed in a large group of patients with choroideraemia. The authors completed a retrospective, cross sectional review of 115 patients with choroideraemia from three tertiary care centres. A longitudinal analysis was performed on 45 of these patients who met the inclusion criteria of at least three visits over a minimum period of 4.5 years. Multiple linear regression analysis was used to explore the 5 year rate of VA change while controlling for initial VA and initial age. Multiple logistic regression was also used to investigate VA impairment. In the cross sectional group (n = 115), 84% (87/103) of patients under the age of 60 had a VA of 20/40 or better while 33% (4/12) of patients 60 years of age or older had a VA of 20/200 or worse at their most recent visit. The majority of the patients (93%) in the longitudinal subgroup of 45 patients had a VA of 20/30 or better at their initial visit. The mean 5 year rate of VA change was 0.09 logMAR equivalent (approximately one line on the Lighthouse chart). In this cohort of patients with choroideraemia, there was typically a slow rate of VA loss and the prognosis for central VA retention was, as a group, favourable until the seventh decade.


4-(1H-Tetra-zol-5-yl)pyridinium bromide.
In the cation of the title compound, C(6)H(6)N(5) (+)·Br(-), the pyridine and tetra-zole rings are nearly coplanar, forming a dihedral angle of 6.41 (2)°. The organic cations inter-act with the Br(-) anions by N-H⋯Br hydrogen bonds, leading to the formation of chains parallel to the b axis.


Novel tRNA gene rearrangements in the mitochondrial genomes of praying mantises (Mantodea: Mantidae): Translocation, duplication and pseudogenization.
Gene rearrangements have been found in several mitochondrial genomes of Mantodea, located in the gene blocks CR-I-Q-M-ND2, COX1-K-D-ATP8 and ND3-A-R-N-S-E-F-ND5. We have sequenced one mitogenome of Amelidae (Yersinia mexicana) and six mitogenomes of Mantidae to discuss the mitochondrial gene rearrangement and the phylogenetic relationship within Mantidae. These mitogenomes showed rearrangements of tRNA genes except for Asiadodis yunnanensis and Hierodula zhangi. These novel gene rearrangements of Mantidae were primarily concentrated in the region of CR-I-Q-M-ND2, including gene translocation, duplication and pseudogenization. For the occurrences of these rearrangements, the tandem duplication-random loss (TDRL) model and slipped-strand mispairing model were suitable to explain. Large non-coding regions (LNCRs) located in the region of CR-I-Q-M-ND2 were detected in most Mantidae species, whereas some LNCRs had high similarity to the control region (CR). Both BI and ML phylogenetic analyses supported the monophyly of Mantidae and the paraphyly of Mantinae. The phylogenetic results with the gene order and the location of NCRs acted as forceful evidence that specific gene rearrangements and special LNCRs may be synapomorphies for several groups of mantises.


A real-time RT-PCR assay for the quantitative determination of adenoviral gene expression in tumor cells.
Oncolytic adenoviruses are exploited as possible anticancer agents in clinical trails. To monitor adenoviral gene expression, a real-time RT-PCR method with a LightCycler was developed that allows the rapid and easy quantification of a number of early and late adenoviral genes in infected tumor cells. Primers were designed that can amplify the spliced forms of the genes encoding E1A13S, DNA polymerase (Pol), pre-terminal protein (pTP), adenoviral death protein (ADP), Hexon (Hex) and Penton (Pent) genes. Standard curves were generated using two-fold serial dilutions of cDNAs derived from non-small cell lung cancer (NSCLC) H460 cells infected for 24h with wild-type adenovirus serotype 5. For all genes correlation coefficients of the standard curves of 0.984 or higher were obtained. The dynamic range of the assay was sufficient to allow the quantitative determination of adenoviral gene expression during a lytic cycle. This RT-PCR assay could be used as a research tool to study the effect of host-cell factors or exogenous treatments on adenoviral gene expression. As example, it is shown that the procedure is suitable to detect changes in adenoviral gene expression in infected H460 cells treated with paclitaxel that is known to enhance the antitumor effect of oncolytic adenoviruses.


The minimal detectable change of the Constant score in impingement, full-thickness tears, and massive rotator cuff tears.
The purpose of this study was to determine the minimal detectable change (MDC) for the Constant score in patients with impingement, a supraspinatus tear, or a massive rotator cuff (RC) tear as observed changes smaller than the MDC might be the result of measurement error. The Constant score was recorded in a total of 180 patients, including 34 patients with impingement, 105 with supraspinatus tears, and 41 with massive RC tears. We assessed the MDC in the 3 subgroups and total group using the samples standard deviation (SD), internal consistency (Cronbach α), and standard error of the measurement. Floor and ceiling effects were also reported. The absolute mean Constant score was 72 (SD, 11.2) in the impingement group, 44 (SD, 14.7) in the supraspinatus tear group, and 46 (SD, 18.9) in the massive RC tear group. There were no floor and ceiling effects for the absolute Constant score. In the total group, the internal consistency was 0.8 and the standard error of the measurement was 8. The MDC was 23 points on the Constant score in the total group and 17, 18, and 23 points on the Constant score for impingement, RC tears, and massive RC tears, respectively. This study demonstrates that the MDCs of the Constant score are different in patients with impingement, supraspinatus tears, and massive RC tears. Studies reporting the Constant score should be interpreted by use of the population-specific MDC and minimal clinical important change.


Effects of Mating on Gene Expression in Female Insects: Unifying the Field.
There is intense interest in controlling insect reproductive output. In many insect species, reproductive output is profoundly influenced by mating, including the receipt of sperm and seminal fluid molecules, through physiological and behavior changes. To understand these changes, many researchers have investigated post-mating gene expression regulation. In this review, we synthesize information from studies both across and within different species about the impact of mating, or components of mating, on female gene expression patterns. We found that genes related to the roles of metabolism, immune-response, and chemosensation are regulated by mating across many different insect species. We highlight the few studies that have taken the important next step of examining the functional consequences of gene expression regulation which is crucial in order to understand the mechanisms underlying the mating-regulated control of female lifespan and reproduction and to make use of such knowledge to propagate or control insect populations. The potential of cross-study comparisons is diminished by different studies using different methods. Thus, we also include a consideration of how future studies could be designed to facilitate cross-study comparisons and a call for collaboration across researchers studying different insect species and different aspects of insect biology.


IgD class switching: identification of a novel recombination site in neoplastic and normal B cells.
IgD on normal B lymphocytes usually is co-expressed with IgM. A minority of normal plasma cells and rare B cell malignancies express exclusively IgD (IgM-IgD+). The low frequency has been explained by the lack of a recognizable switch region within the C mu-C delta intron. We analyzed four cases of IgM-IgD+ hairy cell leukemia (HCL) by Southern (DNA) blot analysis and identified two cases with a recombinatorial event within the C mu-C delta intron and deletion of C mu. DNA sequence analysis of junctional regions showed that S mu or the immediate upstream region was used as a donor site and that the C mu-C delta intronic sigma delta region was used as acceptor site. Using polymerase chain reaction, we subsequently analyzed whether similar S mu-sigma delta recombinations occur in normal tonsils containing IgM-IgD+ plasma cells. Multiple products with a size range of 200-800 base pairs were detected in all four individuals, suggesting clustering of acceptor sites within sigma delta. Sequence analysis of three cloned products showed S mu-sigma delta recombinations similar those observed in HCL. The sigma delta region contains a relatively high content of pentameric repeats with an extremely G-rich area and appears to function as a vestigial switch recombination site in normal and neoplastic IgM-IgD+ B cells.


Usefulness of lymphocyte transformation test and in vitro cytokine release in differentiating between independent and cross-reacting nickel/palladium allergy.
Often concomitant patch test (PT) reactivity to palladium (Pd) and nickel (Ni) is found. To determine whether lymphocyte transformation test (LTT) could be useful in discrimination between cross-reacting or distinct PT results, and to compare the results with in vitro cytokine production upon Pd or Ni stimulation. The study population consisted of two groups: 13 individuals with Pd PT reactions (10 with concomitant Ni PT reaction, 3 individuals with only Pd PT reactivity) and 10 Ni/Pd PT negative individuals. LTT and assessment of cytokine release (interferon-gamma, interleukin-5 [IL-5], IL-8, IL-17A, tumor necrosis factor alpha) by cytometric bead assay were performed. All 10 patients with positive PT to Ni and Pd showed positive LTT to Ni (P < .05) as compared with the 10 Pd/Ni PT negative patients-but had no significant LTT reaction to Pd. In all, 9 out of 10 Pd/Ni PT negative patients were also LTT negative to Ni and 10 out of 10 to Pd. In the 3 only Pd PT reactors 2 out of 3 remained LTT negative to Ni and 0 out of 3 to Pd. As a major finding, cytokine production gave clearly enhanced IL-5 response to Ni in Ni PT positive individuals (P < .05), whereas Pd PT reactivity was not linked with such enhanced IL-5 production in vitro to Pd. Pd and Ni sensitization are mostly found concomitantly, and cross-reactivity is questioned. By different LTT reactions and particularly IL-5 production in vitro, predominant Ni sensitization becomes more evident.


Reasons for non-completion of a massive open online course about multiple sclerosis: A mixed methods study.
Massive open online courses (MOOCs) have grown rapidly in popularity since becoming available worldwide in 2012. There are currently > 30,000 MOOCs available from > 900 universities. However, despite their global reach, MOOCs typically have low completion rates. To evaluate reasons for non-completion among enrolees in the Understanding Multiple Sclerosis (MS) MOOC. This was a mixed methods study evaluating quantitative and qualitative data collected in an online questionnaire administered to Understanding MS enrolees who did not complete the course. The quantitative data was evaluated using frequencies, percentages, means, and standard deviations. The qualitative data was assessed using textual analysis. We recruited 397 participants (4.5% of non-completers). Both the qualitative and quantitative data suggests that the primary reasons for non-completion were time constraints and/or limitations. Some of these were exacerbated by the COVID-19 pandemic. People with MS also cited MS-related symptoms as a reason for non-completion. Suggested changes to the course reflected these results and included extending the course open period and making it self-paced. Although it was impossible to determine if study participants were representative of all non-completers due to selection bias, the results provide useful information for developing future MS educational resources. Accessibility, particularly addressing potential challenges related to MS symptoms and time constraints, should be a primary consideration when developing an educational resource for the MS community.


Acute complicated pyelonephritis: contrast-enhanced ultrasound.
Imaging is required if complication is suspected in acute pyelonephritis to assess the nature and extent of the lesions, and to detect underlying causes. The current imaging modality of choice in clinical practice is computed tomography. Because of associated radiation and potential nephrotoxicity, CEUS is an alternative that has been proven to be equally accurate in the detection of acute pyelonephritis renal lesions. The aims of this study of 48 patients are to describe in detail the CEUS findings in acute pyelonephritis, and to determine if abscess and focal pyelonephritis may be distinguished. Very characteristic morphologic and temporal patterns of enhancement are described. These allow differentiation of focal pyelonephritis from renal abscess, and detection of tiny suppurative foci within focal pyelonephritis. The detection of abscesses is important because follow-up in 25 patients revealed a longer clinical course. Typical pyelonephritis CEUS features permit distinction from other renal lesions. As a whole, CEUS is an excellent tool in the work-up of complicated acute pyelonephritis, so it may be considered as the imaging technique of choice in the evaluation and follow-up of these patients who frequently are very young, so as to minimise radiation exposure.


The hedgehog system machinery controls transforming growth factor-β-dependent myofibroblastic differentiation in humans: involvement in idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a devastating disease of unknown cause. Key signaling developmental pathways are aberrantly expressed in IPF. The hedgehog pathway plays a key role during fetal lung development and may be involved in lung fibrogenesis. We determined the expression pattern of several Sonic hedgehog (SHH) pathway members in normal and IPF human lung biopsies and primary fibroblasts. The effect of hedgehog pathway inhibition was assayed by lung fibroblast proliferation and differentiation with and without transforming growth factor (TGF)-β1. We showed that the hedgehog pathway was reactivated in the IPF lung. Importantly, we deciphered the cross talk between the hedgehog and TGF-β pathway in human lung fibroblasts. TGF-β1 modulated the expression of key components of the hedgehog pathway independent of Smoothened, the obligatory signal transducer of the pathway. Smoothened was required for TGF-β1-induced myofibroblastic differentiation of control fibroblasts, but differentiation of IPF fibroblasts was partially resistant to Smoothened inhibition. Furthermore, functional hedgehog pathway machinery from the primary cilium, as well as GLI-dependent transcription in the nucleus, was required for the TGF-β1 effects on normal and IPF fibroblasts during myofibroblastic differentiation. These data identify the GLI transcription factors as potential therapeutic targets in lung fibrosis.


CCN1 enhances angiogenic potency of bone marrow transplantation in a rat model of hindlimb ischemia.
Implantation of autologous bone marrow mononuclear cells (BM-MNCs) has been performed in ischemic tissues, for stimulation of angiogenesis, but the limited number of BM-MNCs in patients with hindlimb ischemia disease may offset their overall therapeutic efficacy. CCN1 is a novel and essential regulator during angiogenesis. We evaluated whether CCN1 and BM-MNC are capable of promoting angiogenesis in hindlimb ischemia. In this study, we created the rat model of hindlimb ischemia, and then the rats were randomly divided into four groups: CCN1 infusion plus BM-MNC transplantation (CCN1 + BM-MNCs group), CCN1 infusion plus PBS injection (CCN1 group), vehicle infusion plus BM-MNC transplantation (BM-MNCs group) and vehicle infusion plus PBS injection (control group). The combination of CCN1 and BM-MNC therapy could increase blood perfusion, capillary/muscle fiber ratio and tissue oxygenation in ischemic hindlimb. Moreover, CCN1 could not only inhibit the apoptosis of BM-MNCs, but also enhance the adhesiveness of BM-MNCs to HUVEC. Taken together, CCN1 enhanced angiogenesis of BM-MNC transplantation, and combining CCN1 with BM-MNC transplantation is a useful alternative for ischemic limbs.


Earthworm granules: A model of non-classical biogenic calcium carbonate phase transformations.
Different non-classical crystallization mechanisms have been invoked to explain structural and compositional properties of biocrystals. The identification of precursor amorphous nanoparticle aggregation as an onset process in the formation of numerous biominerals (crystallization via particle attachment) constituted a most important breakthrough for understanding biologically mediated mineralization. A comprehensive understanding about how the attached amorphous particles transform into more stable, crystalline grains has yet to be elucidated. Here, we document structural, biogeochemical, and crystallographic aspects of the formation as well as the further phase transformations of the amorphous calcium carbonate particles formed by cultured specimens of earthworm Lumbricus terrestris. In-situ observations evidence the formation of proto-vaterite after dehydration of earthworm-produced ACC, which is subsequently followed by proto-vaterite transformation into calcite through nanoparticle attachment within the organic framework. In culture medium spiked with trace amounts of Mn2+, the cauliflower-like proto-vaterite structures become longer-lived than in the absence of Mn2+. We propose that the formation of calcite crystals takes place through a non-classical recrystallization path that involves migration of proto-vaterite nanoparticles to the crystallization site, and then, their transformation into calcite via a dissolution-recrystallization reaction. The latter is complemented by ion-by-ion crystal growth and associated with impurity release. These observations are integrated into a new model of the biocrystallization of earthworm-produced carbonate granules which highlights the sensibility of this process to environmental chemical changes, its potential impact on the bioavailability of contaminants as well as the threat that chemical pollution poses to the normal development of its early stages. STATEMENT OF SIGNIFICANCE: Understanding the mechanisms of nucleation, stabilization and aggregation of amorphous calcium carbonate (ACC) and factors controlling its further transformation into crystalline phases is fundamental for elucidation of biogenic mineralization. Some species of earthworms are natural workbench to understand the biogenic ACC, stabilization and the transformation mechanisms, because they create millimeter-sized calcareous granules from amorphous calcium carbonate, which crystallize to a more stable mineral phase (mostly calcite). This study undergoes into the mechanisms of ACC stabilization by the incorporation of trace elements, as manganese, and the ulterior precipitation of calcareous granules by a coupled process of amorphous particle attachment and ion-by-ion growth. The study points to sensibility of this process to environmental chemical changes.


Diagnostic accuracy of three commercially available one step RT-PCR assays for the detection of SARS-CoV-2 in resource limited settings.
COVID-19 is an ongoing public health pandemic regardless of the countless efforts made by various actors. Quality diagnostic tests are important for early detection and control. Notably, several commercially available one step RT-PCR based assays have been recommended by the WHO. Yet, their analytic and diagnostic performances have not been well documented in resource-limited settings. Hence, this study aimed to evaluate the diagnostic sensitivities and specificities of three commercially available one step reverse transcriptase-polymerase chain reaction (RT-PCR) assays in Ethiopia in clinical setting. A cross-sectional study was conducted from April to June, 2021 on 279 respiratory swabs originating from community surveillance, contact cases and suspect cases. RNA was extracted using manual extraction method. Master-mix preparation, amplification and result interpretation was done as per the respective manufacturer. Agreements between RT-PCRs were analyzed using kappa values. Bayesian latent class models (BLCM) were fitted to obtain reliable estimates of diagnostic sensitivities, specificities of the three assays and prevalence in the absence of a true gold standard. Among the 279 respiratory samples, 50(18%), 59(21.2%), and 69(24.7%) were tested positive by TIB, Da An, and BGI assays, respectively. Moderate to substantial level of agreement was reported among the three assays with kappa value between 0 .55 and 0.72. Based on the BLCM relatively high specificities (95% CI) of 0.991(0.973-1.000), 0.961(0.930-0.991) and 0.916(0.875-0.952) and considerably lower sensitivities with 0.813(0.658-0.938), 0.836(0.712-0.940) and 0.810(0.687-0.920) for TIB MOLBIOL, Da An and BGI respectively were found. While all the three RT-PCR assays displayed comparable sensitivities, the specificities of TIB MOLBIOL and Da An were considerably higher than BGI. These results help adjust the apparent prevalence determined by the three RT-PCRs and thus support public health decisions in resource limited settings and consider alternatives as per their prioritization matrix.


Organizing, exploring, and analyzing antibody sequence data: the case for relational-database managers.
Technological advances in the acquisition of DNA and protein sequence information and the resulting onrush of data can quickly overwhelm the scientist unprepared for the volume of information that must be evaluated and carefully dissected to discover its significance. Few laboratories have the luxury of dedicated personnel to organize, analyze, or consistently record a mix of arriving sequence data. A methodology based on a modern relational-database manager is presented that is both a natural storage vessel for antibody sequence information and a conduit for organizing and exploring sequence data and accompanying annotation text. The expertise necessary to implement such a plan is equal to that required by electronic word processors or spreadsheet applications. Antibody sequence projects maintained as independent databases are selectively unified by the relational-database manager into larger database families that contribute to local analyses, reports, interactive HTML pages, or exported to facilities dedicated to sophisticated sequence analysis techniques. Database files are transposable among current versions of Microsoft, Macintosh, and UNIX operating systems.


Effects of sludge morphology on the anammox process: Analysis from the perspectives of performance, structure, and microbial community.
The nitrogen removal characteristics, physicochemical properties, and microbial community composition of four different anaerobic ammonium oxidation (anammox) sludge morphologies were investigated. The morphologies considered in this study, namely suspended sludge (Rs), biofilm (Rm), granular sludge (Rg), and encapsulated biomass (Re), were prepared from floc sludge. The results show that Re exhibited the maximum anammox activity, followed by Rg, Rm, and Rs. Additionally, the anammox contribution rate was higher in Rg and Re. The higher extracellular polymer content in Rg promoted sludge accumulation, and tryptophan was observed in Rm and Rg, which was replaced by humic acids in Rs. Re showed the largest specific surface area, hydrophobicity and strength, and its good structure ensured enrichment of anammox bacteria (AnAOB). In terms of the microbial community, the functional bacterium Candidatus Kuenenia accounted for the highest proportion in Rm (39.27%), but the presence of both anaerobic and aerobic regions led to increased community complexity with more nitrifying bacteria. In contrast, Rg and Re had a more specific microbial community. In addition, denitrifying bacteria tended to grow in Rs, while nitrifying bacteria were retained in Rm. The AnAOB were more likely to be enriched in sludge aggregates (both Rm and Rg) and carriers (Re). Through correlation analysis, the potential relationship involving bacterial flora evolution of each sample was clarified. Finally, the structural models of different morphologies of sludge were proposed. This study deepens the understanding of various anammox sludge morphologies as well as provides useful information for the cultivation of AnAOB and further application of anammox.


The impact of death and dying on the personhood of medical students: a systematic scoping review.
The re-introduction of medical students into healthcare systems struggling with the COVID-19 pandemic raises concerns as to whether they will be supported when confronted with death and dying patients in resource-limited settings and with reduced support from senior clinicians. Better understanding of how medical students respond to death and dying will inform educationalists and clinicians on how to best support them. We adopt Krishna's Systematic Evidence Based Approach to carry out a Systematic Scoping Review (SSR in SEBA) on the impact of death and dying on medical students. This structured search process and concurrent use of thematic and directed content analysis of data from six databases (Split Approach) enhances the transparency and reproducibility of this review. Seven thousand six hundred nineteen were identified, 149 articles reviewed and 52 articles included. The Split Approach revealed similar themes and categories that correspond to the Innate, Individual, Relational and Societal domains in the Ring Theory of Personhood. Facing death and dying amongst their patients affect how medical students envisage their personhood. This underlines the need for timely, holistic and longitudinal support systems to ensure that problems faced are addressed early. To do so, there must be effective training and a structured support mechanism.


The effect of a color tattoo on the local skin redox regulatory network: an N-of-1 study.
Biomedical aspects of tattooing have been extensively discussed in literature, however pathophysiological effects of tattoo inks in the human body are still unexplored. Oxidative stress is considered responsible for the adverse effects of tattooing, however no experimental evidence for tattoo ink-related oxidative stress in the human body currently exists. The aim was to examine the effect of a blue tattoo on skin redox regulatory network (RRN) parameters in a single human subject. Skin surface oxidation-reduction potential (ORP) was analyzed with a PH60F flat probe. Interstitial and intracellular fluid enriched capillary blood from the tattoo and the control area was extracted and analyzed with I2/KI-stabilized microORP, nitrocellulose redox permanganometry (NRP), carbonato-cobaltate (III) formation-derived H2O2 dissociation rate assay, 1,2,3-trihydroxybenzene autoxidation assay, thiobarbituric reactive substances (TBARS) assay and 5,5,'-dithio-bis-(2-nitrobenzoic acid) (DTNB)-based determination of free thiol content in low molecular weight and protein precipitate fractions. Surface ORP analysis revealed a greater antioxidant capacity of tattooed skin in comparison with the control (CTR). Capillary blood analysis confirmed greater reductive capacity in the tattoo sample both by microORP (-4.33 mV vs CTR) and NRP (+10.8%). Hydrogen peroxide dissociation rate (+11.8%), and protein sulfhydryl content (+8.5%) were increased, and lipid peroxidation (-15%) was reduced in the tattoo sample in comparison with the CTR. In this N-of-1 study, RRN of tattooed skin was shifted toward a more reductive state with all parameters indicating reduced levels of oxidative stress in comparison with nontattooed skin. The local antioxidant effect of copper(II) phthalocyanine provides one possible explanation of the observed effects.


Effectiveness of biofeedback relaxation and audio-visual distraction on dental anxiety among 7- to 12-year-old children while administering local anaesthesia: A randomized clinical trial.
Local anaesthesia (LA) administration provokes dental anxiety in children. BrightHearts is a biofeedback relaxation application designed to reduce anxiety in children during painful procedural interventions. To compare the effectiveness of biofeedback relaxation (BR) and audio-visual (AV) distraction on dental anxiety among 7- to 12-year-old children while administering LA. A total of 70 children requiring dental treatment under LA for three visits were recruited for this single-blinded randomized control trial. They were randomly divided into two equal groups. Group A received BR and Group B received AV distraction during LA delivery in the first two visits, and both groups did not receive any intervention during LA in third visit. Outcomes were measured using heart rate and a cartoon-based anxiety measuring scale (Chotta Bheem-Chutki (CBC) scale). AV group had statistically significant higher mean heart rates than BR group (P < .001) during needle penetration and post-intervention, respectively. CBC scale showed no statistical differences between the groups. Both the interventions are effective in reducing dental anxiety during LA administration. Based on objective measures, BR is found to be better than AV distraction. Subjective scores, however, show no differences between the two.


ARHGAP10 inhibits the epithelial-mesenchymal transition of non-small cell lung cancer by inactivating PI3K/Akt/GSK3β signaling pathway.
Rho GTPase activating protein 10 (ARHGAP10) has been implicated as an essential element in multiple cellular process, including cell migration, adhesion and actin cytoskeleton dynamic reorganization. However, the correlation of ARHGAP10 expression with epithelial-mesenchymal transition (EMT) in lung cancer cells is unclear and remains to be elucidated. Herein, we investigated the relationship between the trait of ARHGAP10 and non-small cell lung cancer (NSCLC) pathological process. Immunohistochemistry was conducted to evaluate the expression of ARHGAP10 in NSCLC tissues. CCK-8 assays, Transwell assays, scratch assays were applied to assess cell proliferation, invasion and migration. The expression levels of EMT biomarkers and active molecules involved in PI3K/Akt/GSK3β signaling pathway were examined through immunofluorescence and Western blot. ARHGAP10 was detected to be lower expression in NSCLC tissues compared with normal tissues from individuals. Moreover, overexpression of ARHGAP10 inhibited migratory and invasive potentials of A549 and NCI-H1299 cells. In addition, ARHGAP10 directly mediated the process of EMT via PI3K/Akt/GSK3β pathway. Meanwhile, activation of the signaling pathway of insulin-like growth factors-1 (IGF-1) reversed ARHGAP10 overexpression regulated EMT in NSCLC cells. ARHGAP10 inhibits the epithelial-mesenchymal transition in NSCLC via PI3K/Akt/GSK3β signaling pathway, suggesting agonist of ARHGAP10 may be an optional remedy for NSCLC patients than traditional opioids.


Notch activation promotes endothelial quiescence by repressing MYC expression via miR-218.
After angiogenesis-activated embryonic and early postnatal vascularization, endothelial cells (ECs) in most tissues enter a quiescent state necessary for proper tissue perfusion and EC functions. Notch signaling is essential for maintaining EC quiescence, but the mechanisms of action remain elusive. Here, we show that microRNA-218 (miR-218) is a downstream effector of Notch in quiescent ECs. Notch activation upregulated, while Notch blockade downregulated, miR-218 and its host gene Slit2, likely via transactivation of the Slit2 promoter. Overexpressing miR-218 in human umbilical vein ECs (HUVECs) significantly repressed cell proliferation and sprouting in vitro. Transcriptomics showed that miR-218 overexpression attenuated the MYC proto-oncogene, bHLH transcription factor (MYC, also known as c-myc) signature. MYC overexpression rescued miR-218-mediated proliferation and sprouting defects in HUVECs. MYC was repressed by miR-218 via multiple mechanisms, including reduction of MYC mRNA, repression of MYC translation by targeting heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), and promoting MYC degradation by targeting EYA3. Inhibition of miR-218 partially reversed Notch-induced repression of HUVEC proliferation and sprouting. In vivo, intravitreal injection of miR-218 reduced retinal EC proliferation accompanied by MYC repression, attenuated pathological choroidal neovascularization, and rescued retinal EC hyper-sprouting induced by Notch blockade. In summary, miR-218 mediates the effect of Notch activation of EC quiescence via MYC and is a potential treatment for angiogenesis-related diseases.


Salivary Glands and Periodontal Changes in a Population of Sjögren's and Sicca Syndrome Treated by Pilocarpine: A Pilot Study.
Oral administration of pilocarpine enhances salivary flow in sicca patients but its effect upstream on ultrasound (US) of salivary glands (SG) and downstream on periodontium remain unknown. Sicca patients were prospectively included. Echostructural and vascularization of SG were assessed using B mode and pulsed Doppler (USPD). Vascularization of SG was measured using resistive index (RI) before and after stimulation by lemon juice. Echostructure (measure of glandular length in cm2, evaluation of parotid and submandibular glands parenchymal abnormalities) was assessed at baseline (M0) and after 3 months (M3) of treatment with pilocarpine. A dental consultation was performed at M0 and M3 to evaluate changes in unstimulated salivary flow (USSF), stimulated salivary flow (SSF), and periodontal parameters such as modified gingival index (Lobene), plaque index (Silness), bleeding index, pocket depth, and pH. Nineteen patients were included but only 11 received pilocarpine treatment for 3 months, as six stopped pilocarpine due to side effects and two were excluded for other causes. Among the 11 patients who completed the 3-month follow-up, five had primary Sjögren's syndrome according to the American-European's classification criteria. As expected, statistical differences were found concerning SSF (p = 0.018) and USSF (p = 0.027) between M0 and M3 while no statistical change in both SG echostructure and vascularization or periodontal evaluation was shown. Pilocarpine improved SSF and USSF measurements in sicca syndrome but no ultrasonography of major salivary glands (SGUS) structural and vascular changes were detected as well as periodontal evaluation.


Enhancement of colony forming ability in the lung by transfer of the v-fos oncogene into a ras-transformed rat 3Y1 cell line.
Transfer of the v-fos oncogene into a rat 3Y1 cell line transformed by v-H-ras, which is tumorigenic but non-metastatic, enhanced lung metastasis, depending on the amount of fos-related transcripts. Enhancement of the metastatic potential was associated with increases in tumor growth rate i.m. of inoculated cells but not the rate of in vitro cell growth, irrespective of the addition of tissue (e.g. lung) extract to the regular medium. These results suggest that the v-fos oncogene increased the malignancy by altering biological factors of the recipient cells responsible for cell growth and/or survival rate in vivo.


Glial-Neuronal Interactions in Neurological Disorders: Molecular Mechanisms and Potential Points for Intervention.
Neurons have long been central to the study of cellular networks in the nervous system [...].


Extra-axial soft tissue chordoma of wrist.
Extra-axial soft tissue chordoma is rare. We report a case of extra-axial soft tissue chordoma of the right wrist in an 87-year-old man. The tumor was large, and the cut surface showed multinodular and myxoid appearance. Microscopically, nests of epithelioid and spindle cells were observed in the myxoid matrix. Vacuolated cells were also observed. The tumor cells were diffusely positive for brachyury and cytokeratin 19 on immunohistochemistry, suggesting that the tumor was extra-axial soft tissue chordoma. Extra-axial chordoma is the same entity as chordoma periphericum (parachordoma), as proposed by Laskowski and Dabska.


Peripheral nerves in early experimental diabetes: expansion of the endoneurial space as a cause of increased water content.
The aim of the present study was to examine whether the nerve water content and the Schwann cell cytoplasm are increased in early experimental diabetics, as suggested in the sorbitol theory. The sciatic nerves of streptozotocin diabetic rats were found to have an increased wet weight. The amount of Schwann cell cytoplasm was reduced by 30%. The increased wet weight was paralleled by enlargement of the cross sectional area of the nerve which was explained by an expansion of the endoneurial space. The findings indicate the existence of endoneurial oedema and are in part in conflict with the sorbitol theory. Extension of the space surrounding the nerve fibres may explain the increased resistance to ischaemia in diabetic patients.


Platinum nanoparticles reduce ovariectomy-induced bone loss by decreasing osteoclastogenesis.
Platinum nanoparticles (PtNP) exhibit remarkable antioxidant activity. There is growing evidence concerning a positive relationship between oxidative stress and bone loss, suggesting that PtNP could protect against bone loss by modulating oxidative stress. Intragastric administration of PtNP reduced ovariectomy (OVX)- induced bone loss with a decreased level of activity and number of osteoclast (OC) in vivo. PtNP inhibited OC formation by impairing the receptor activator of nuclear factor-κB ligand (RANKL) signaling. This impairment was due to a decreased activation of nuclear factor-κB and a reduced level of nuclear factor in activated T-cells, cytoplasmic 1 (NFAT2). PtNP lowered RANKL-induced long lasting reactive oxygen species as well as intracellular concentrations of Ca(2+) oscillation. Our data clearly highlight the potential of PtNP for the amelioration of bone loss after estrogen deficiency by attenuated OC formation.


Taiwanese dermatological association consensus for the definition, classification, diagnosis, and management of urticaria: A 2021 update.
Urticaria is a prevalent disease with substantial physical, psychological, and economic impacts. With the advent of understandings of the disease and the emerging evidence of treatments, the international guidelines for treating urticaria have been updated in recent years. In order to update the 2014 edition of the Taiwanese Dermatological Association (TDA) consensus of urticaria, a total of 17 dermatologists with extensive experience in urticaria management were invited to and attended the TDA consensus meetings. All the specific aspects of the content were approved by at least 75% of the experts in attendance. Comparing to the former edition, several substantial modifications were made. For diagnosis, D-dimer was added as the recommended routine test in patients with chronic spontaneous urticaria. For pharmacological management, treatment suggestions were simplified. The approved-dosed, the up-dosed second-generation antihistamines, omalizumab, and cyclosporine were listed as the first-line to the fourth-line treatment, respectively. In addition, the management for patients of special considerations, such as the elderly, children, and pregnant women, were all discussed and mentioned in the consensus. We hope the updated TDA consensus can serve as a reference for all physicians and can help the physicians providing up-to-dated managements for these patients.


Geriatric assessment in older adults with non-Hodgkin lymphoma: A Young International Society of Geriatric Oncology (YSIOG) review paper.
Non-Hodgkin lymphoma (NHL) is a disease of older adults, with a median age at diagnosis of 67 years. Treatment in older adults with NHL is challenging. The aging process is associated with a decline in functional reserve that varies among individuals, and results in an increasing risk of treatment-related toxicity and mortality. Chronological age and performance status fail to capture the multidimensional and heterogeneous nature of the aging process. A geriatric assessment (GA) screens multiple geriatric domains and provides a more accurate assessment of functional reserve. Several abbreviated GA tools have been developed for use in oncology clinics and help identify patients at high risk for chemotherapy-related toxicity and mortality. In this review, we explore GA tools validated for use in patients with NHL. We discuss the evidence behind GA-guided treatment in NHL and present a suggested approach to assessing frailty in this patient population.


Determinants of delay in malaria treatment-seeking behaviour for under-five children in south-west Ethiopia: a case control study.
Prompt diagnosis and timely treatment of malaria within 24 hours after onset of first symptoms can reduce illness progression to severe stages and therefore, decrease mortality. The reason why mothers/caretakers delay in malaria diagnosis and treatment for under-five children is not well studied in Ethiopia. The objective of this study was to assess determinants of malaria treatment delay in under-five children in three districts of south-west Ethiopia. A case control study was conducted from March 15 to April 20, 2010. Cases were under-five children who had clinical malaria and sought treatment after 24 hours of developing sign and symptom, and controls were under-five children who had clinical malaria and sought treatment within 24 hours of developing sign and symptom of malaria. Data were collected by trained enumerators using structured questionnaire. Data were entered in to Epi Info version 6.04 and analyzed using SPSS version 16.0. To identify determinants, multiple logistic regression was done. A total of 155 mothers of cases and 155 mothers of controls were interviewed. Mothers of children who were in a monogamous marriage (OR = 3.41, 95% CI: 1.39, 8.34), who complained about the side effects of anti-malarial drugs (OR = 4.96, 95% CI: 1.21, 20.36), who had no history of child death (OR = 3.50, 95% CI: 1.82, 6.42) and who complained about the higher cost of transportation to reach the health institutions (OR = 2.01, 95% CI: 1.17, 3.45) were more likely to be late for the treatment of malaria in under-five children. Effective malaria control programmes should address reducing delayed presentation of children for treatment. Efforts to reduce delay should address transport cost, decentralization of services and increasing awareness of the community on early diagnosis and treatment.


A simple four-factor preoperative recipient scoring model for prediction of 90-day mortality after adult liver Transplantation:A retrospective cohort study.
Although numerous scoring models are available to predict the prognosis of patients undergoing liver transplantation (LT), the field lacks a simple model for quick prediction of the short-term survival of patients after LT in the event that the donor's information is not available in advance. A total of 1495 adult patients underwent LT in the present study. Three-quarters of recipients were randomly selected into the test set (n = 1121), while the remaining 25% formed the validation set (n = 374). Univariate and multivariate analysis and machine-learning techniques were applied to evaluate possible influencing factors. To further simplify the model, a weighted-scoring system was designed considering each influencing factor and its importance in an artificial neural network (ANN). In the test set, multivariate analysis identified creatinine, age, and total bilirubin as independent risk factors, while albumin was an independent protective factor. Logistic regression analysis showed the C-statistic to be 0.650, while ANN indicated this to be 0.698. We simplified the model to obtain the final scoring model, for which the C-statistic was 0.636, and defined four risk grades. The 90-day mortality rates corresponding to the four risk levels were 6.2%, 11.8%, 24.0%, and 34.9%, respectively. In the validation set, the C-statistic value of the original model was 0.668 and that of the simplified model was 0.647. We developed a simple scoring system for the preliminary prediction of the postoperative 90-day mortality of adult LT based on preoperative characteristics of LT recipients.


Individualized surgery combined with radiotherapy and triamcinolone acetonide injection for the treatment of auricular keloids.
Although multiple methods have been proposed to treat auricular keloids, low curative effects and high recurrence rates are currently major clinical problems. Thereinto, surgery combined with radiotherapy and triamcinolone acetonide injection is considered to be the proper choice for comprehensive treatment of auricular keloids. This study aimed at evaluating the therapeutic effect of individualized surgery combined with radiotherapy for the treatment of auricular keloids. From February 2014 to February 2017, 67 patients with 113 auricular keloids in total were enrolled in this study. According to specific conditions of lesions, the local tissue and patients' individual wishes, different surgical methods were selected to analyze the scar excision and repairment of the defect. Within 24 h after the keloid was excised, 5 MeV electron beam irradiation by the linear accelerator was used by radiotherapy with a total dose of 20 Gy at interval of 1 day for 10 consecutive times. Triamcinolone acetonide was injected immediately after surgery, and per month afterward in the following three months. 113 keloids in total were received treatment. The follow-up period was 24 months. Fourteen keloids (12.39%) showed subjective recurrence with a success rate of 87.61%. Wilcoxon matched-pairs rank-sum test was used to compare the differences of the 24-month postoperative VSS scores and the preoperative VSS scores. The VSS scores were as follows: 82 keloids (72.57%) scored less than 5 points (good result), 21 keloids (18.58%) scored 6 to 10 points (fair result), and only 10 keloids (8.85%) scored more than 10 points (bad result). The effective rate was 91.15%. Individualized surgery combined with early postoperative radiotherapy and triamcinolone acetonide injection is an ideal treatment method to ensure good auricular appearance, low incidences of complications and recurrence based on effective treatment of auricular keloids.


Curcumin induces expression of 15-hydroxyprostaglandin dehydrogenase in gastric mucosal cells and mouse stomach in vivo: AP-1 as a potential target.
15-Hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes the conversion of oncogenic prostaglandin E2 to non-tumerigenic 15-keto prostaglandin E2. In the present study, we found that curcumin, a yellow coloring agent present in the rhizome of Curcuma longa Linn (Zingiberaceae), induced expression of 15-PGDH at the both transcriptional and translational levels in normal rat gastric mucosal cells. By using deletion constructs of 15-PGDH promoter, we were able to demonstrate that activator protein-1 (AP-1) is the principal transcription factor responsible for regulating curcumin-induced 15-PGDH expression. Curcumin enhanced the expression of c-Jun and c-Fos that are functional subunits of AP-1, in the nuclear fraction of cells. Silencing of c-Jun suppressed curcumin-induced expression of 15-PGDH. Moreover, the chromatin immunoprecipitation assay revealed curcumin-induced binding of c-Jun to the AP-1 consensus sequence present in the 15-PGDH promoter. Curcumin increased phosphorylation of ERK1/2 and JNK, and pharmacologic inhibition of these kinases abrogated the curcumin-induced phosphorylation of c-Jun and 15-PGDH expression. In contrast, tetrahydrocurcumin which lacks the α,β-unsaturated carbonyl group failed to induce 15-PGDH expression, suggesting that the electrophilic carbonyl group of curcumin is essential for its induction of 15-PGDH expression. Curcumin restored the expression of 15-PGDH which is down-regulated by Helicobacter pylori through suppression of DNA methyltransferase 1. In addition, oral administration of curcumin increased the expression of 15-PGDH and its regulators such as p-ERK1/2, p-JNK, and c-Jun in the mouse stomach. Taken together, these findings suggest that curcumin-induced upregulation of 15-PGDH may contribute to chemopreventive effects of this phytochemical on inflammation-associated gastric carcinogenesis.


The utility of Vibratip in accurate identification of loss of protective sensation in the contralateral foot of patients admitted with a diabetic foot ulcer.
Diabetic foot ulcer (DFU) is a debilitating complication of type 2 DM. Complexity of foot examination often precludes proper clinical assessment of the foot during routine evaluation. We assessed the utility of novel device, vibratip, both singly and in combination with standard bedside tools for assessment of loss of protective sensation. 75 patients admitted with DFU were included in the study. Clinical examination of the contralateral foot was done - temperature perception, vibration, pinprick sensation, Achilles tendon reflex and Neuropathy disability score were assessed. Testing using 10 g Monofilament, Vibratip and biothesiometer were also done. Considering the biothesiometer as the reference standard, three bedside tests (Vibratip, 10 g monofilament and 128 Hz tuning fork) were compared against it singly and in combinations. When compared against biothesiometer, vibratip performed significantly well with a positive predictive value of 90.3% and specificity of 84.2%. Sensitivity, however, was only 50%. On combining bedside tests, the best combination strategy was seen with vibratip and 10 g monofilament, which improved the sensitivity to 62.5%. Combining all three bedside tests further improved sensitivity to 64.3%. All the patients with an at-risk foot may not be identified with vibratip alone. Nevertheless, an abnormal result is almost always associated with loss of protective sensation, and such persons should be suitably educated. Due to small size of the study population, it is not possible to generalize the findings to all patients with diabetes mellitus. A larger study would be required to provide more confirmatory findings.


Mechanisms of impulsive choice: II. Time-based interventions to improve self-control.
Impulsive choice behavior has been proposed as a primary risk factor for other maladaptive behaviors (e.g., gambling, substance abuse). Recent research has suggested that timing processes may play a key role in impulsive choice behavior, and could provide an avenue for altering impulsive choice. Accordingly, the current experiments assessed a set of time-based behavioral interventions to increase self-control while simultaneously assessing effects on timing processes within the impulsive choice task. Three experiments assessed temporal interventions using a differential reinforcement of low rates task (Experiment 1) and exposure to either a variable or fixed interval schedule (Experiments 2-3). The efficacy of the interventions was assessed in Sprague-Dawley (Experiments 1-2) and Lewis (Experiment 3) rat strains. Impulsive choice behavior was assessed by measuring preferences of a smaller-sooner (SS) versus a larger-later (LL) reward, while timing of the SS and LL durations was measured during peak trials within the impulsive choice procedure. The rats showed an increased preference for the LL following all three time-based interventions and also displayed increased temporal precision. These results add to the increasing evidence that supports a possible role for temporal processing in impulsive choice behavior and supply novel behavioral interventions to decrease impulsive behavior.


Safety huddles in the PACU: when a patient self-medicates.
The implementation of safety huddles in the PACU has been effective in enhancing and promoting patient safety during the recovery period. The case scenario presented in this article demonstrates how the safety huddle can be used to examine nursing care in the PACU. Allotting time each day to address patient-related issues that arise during patient care allows the team to troubleshoot and resolve clinical issues. Through examination of nursing practices in the recovery period, PACU nurses are able to support the best perianesthesia care possible.


Use of normal saline and incidence of dyselectrolytaemia in children following kidney transplantation.
The use of hypotonic fluid, such as 0.45% saline, following kidney transplantation (KT) in children is associated with a high incidence of electrolyte imbalance, especially hyponatraemia. This can result in serious adverse events, such as cerebral oedema and seizures. The aim of this study was to investigate the incidence of electrolyte disturbance in children when 0.9% saline was the intravenous fluid used in the first 72 h following KT. This is a retrospective, observational study of 50 consecutive KT undertaken between January 2017 and January 2019 at a single centre. The median age at KT was 9.2 years (IQR 4-14) and 16 (32%) were females. Thirty-two (64%) were living related donor (LRD) KT and 22 (44%) were carried out in children < 20 kg. The mean volume of fluid administered intra-operatively, and on Day 1, Day 2 and Day 3, were 73 ml/kg, 124 ml/kg, 97 ml/kg and 86 ml/kg, respectively. Hyponatraemia was noted in 4%, hypernatraemia in 18%, hyperkalaemia in 18%, hyperchloraemia in 68% and low bicarbonate was seen in 88%. Fifteen percent of the children had an episode of hyperglycaemia. None of the children developed symptomatic dyselectrolytaemia. There was delayed graft function (DGF) in 4 (8%) recipients - all deceased donor (DD) KT, including 2 who received donations after circulatory death. While the use of 0.9% saline is associated with a high incidence of electrolyte disturbances, including hyperkalaemia, it reduces the risk of hyponatraemia. None of the children developed a symptomatic electrolyte abnormality. A higher resolution version of the Graphical abstract is available as Supplementary information.


[Association of the insulin-like growth factor II (IGF2) gene with human cognitive functions].
Active search for candidate genes whose polymorphisms are associated with human cognitive functions has been in progress in the past years. The study focused on the role that the insulin-like growth factor II (IGF2) gene may play in the variation of cognitive processes related to executive functions. The ApaI polymorphism of the IGF2 gene was tested for association with selective attention during visual search, working memory/mental control, and semantic verbal fluency in a group of 182 healthy individuals. The ApaI polymorphism was associated with the general cognitive index and selective attention measure. Carriers of genotype AA displayed higher values of the two parameters than carriers of genotype GG. It was assumed that the ApaI polymorphism of the IGF2 gene influences the human cognitive functions, acting possibly via modulation of the IGF-II level in the central nervous system.


Altered neural correlates of reward and loss processing during simulated slot-machine fMRI in pathological gambling and cocaine dependence.
Individuals with gambling or substance-use disorders exhibit similar functional alterations in reward circuitry suggestive of a shared underlying vulnerability in addictive disorders. Additional research into common and unique alterations in reward-processing in substance-related and non-substance-related addictions may identify neural factors that could be targeted in treatment development for these disorders. To investigate contextual reward-processing in pathological gambling, a slot-machine fMRI task was performed by three groups (with pathological gambling, cocaine dependence and neither disorder; N = 24 each) to determine the extent to which two groups with addictions (non-substance-related and substance-related) showed similarities and differences with respect to each other and a non-addicted group during anticipatory periods and following the delivery of winning, losing and 'near-miss' outcomes. Individuals with pathological gambling or cocaine dependence compared to those with neither disorder exhibited exaggerated anticipatory activity in mesolimbic and ventrocortical regions, with pathological-gambling participants displaying greater positive possible-reward anticipation and cocaine-dependent participants displaying more negative certain-loss anticipation. Neither clinical sample exhibited medial frontal or striatal responses that were observed following near-miss outcomes in healthy comparison participants. Alterations in anticipatory processing may be sensitive to the valence of rewards and content-disorder-specific. Common and unique findings in pathological gambling and cocaine dependence with respect to anticipatory reward and near-miss loss processing suggest shared and unique elements that might be targeted through behavioral or pharmacological interventions in the treatment of addictions.


Soft Tissue Coverage After Revisional Foot and Ankle Surgery.
Unlike the traumatic "mangled" foot and ankle in which amputation could be an acceptable if not preferred option, revisional foot and ankle surgery starts with a viable foot that is then injured by the surgeon hopefully to benefit the patient. Any untoward sequela, such as inadequate wound healing, instead always requires consideration of limb salvage. Unfortunately, this may not be so simple. A proactive approach to solve this problem in a timely fashion is important. The goal must always be to get a healed wound so the final result improves the ability for independent ambulation by the patient.


Characterization of synectin expression and promoter activity.
Synectin, a PDZ2 protein, binds to a number of plasma membrane receptors. We characterized synectin promoter and carried out a detailed expression survey. The protein is widely distributed in adult cells and tissues. Expression in the mouse embryo is apparent at day 4.5, peaks at day 12.5 and declines to its adult levels by day 18.5. The level of synectin transcription was minimally affected by exposure to cytokines, growth factors or hypoxia. In summary, synectin's early appearance, constant nature, and ubiquitous distribution suggest that it may be a key structural protein involved in mediation of outside-in signaling.


[The efficacy of alimemazine (solution for intramuscular injection) in complex with antidepressants in the treatment of anxiety and depressive disorders].
To evaluate the efficacy of alimemazine in the form of a solution for intramuscular injections in the treatment of anxiety and depressive disorders. Twenty patients, who met ICD-10 criteria for anxiety and depressive disorders, participated in the clinical observation. Alimemazine was used in the form of a solution for intramuscular injection (5 mg/ml) along with SSRIs and SNRIs. The significant positive dynamics in the reduction of anxiety-depressive disorders, sleep disorders and vegetative symptoms was observed in patients treated with alimemazine (solution) and antidepressants from the group of SSRIs and SSRIs. The drug has demonstrated efficacy and a favorable tolerability profile.


[Granulomatous uveitis and CREST syndrome: a case study].
To report a case of recurrent granulomatous panuveitis associated with CREST syndrome. A 74-year-old patient with CREST syndrome presented with unilateral granulomatous panuveitis in a pseudophakic eye. She had undergone cataract surgery 6 months before. The patient reported a vision loss that had been evolving for 1 month. Visual acuity was noted at 20/400. The initial clinical examination highlighted retrodescemetic precipitates and granulomatous precipitates on the IOL. A vitreous tyndall was noted. Funduscopic examination revealed papillary edema and cystoid macular edema, confirmed by fluorescein angiography. Topical treatment consisting in corticosteroid eye drops associated with mydriatics controlled uveitis in a few weeks. Visual recovery was 20/30. No granulomatous uveitis etiology could be highlighted. The diagnosis of chronic endophthalmitis was also ruled out. The diagnosis retained was uveitis associated with CREST syndrome. To our knowledge, this association has only been reported twice in the literature.


Multidrug resistance to antimicrobials as a predominant factor influencing patient survival.
The impact of multidrug resistance to antimicrobials was assessed in a cohort of 243 patients with microbiologically documented infections by a variety of susceptible and multidrug-resistant (MDR) species. Multidrug resistance was defined as resistance to more than two antimicrobial agents of different chemical structure. Cox regression analysis was performed to define differences and the significance of any predisposing factors. Overall survival of patients infected by susceptible isolates was prolonged compared with patients infected by MDR isolates (P=0.013). Mortality rates of infections caused by susceptible and MDR isolates were 4.87% and 16.15%, respectively (P=0.013); the higher mortality rate for MDR isolates was more pronounced for infections by Klebsiella pneumoniae and Pseudomonas aeruginosa. Mean (+/-standard error (S.E.)) survival of patients infected by susceptible and MDR isolates in patients without signs of severe sepsis was 28 days and 27.29+/-0.35 days, respectively (P=not significant). Mean (+/-S.E.) survival of patients with severe sepsis caused by susceptible and MDR isolates was 7.70+/-4.62 days and 10.45+/-2.18 days, respectively (P=0.048). Diabetes mellitus type 2, the presence of severe sepsis and any underlying malignancy were the most important risk factors affecting survival. It is concluded that infections by MDR isolates were accompanied by higher mortality rates and decreased survival compared with infections by susceptible isolates. Diabetes mellitus type 2 and underlying malignancies were significant co-morbid conditions, whereas survival after infection by susceptible isolates was particularly decreased in the event of severe sepsis.


Effect of fetal and maternal intravascular antipyrine infusion on maternal plasma prostaglandin concentrations in the pregnant sheep at 104 to 127 days' gestation.
Antipyrine is commonly used to measure umbilical and uterine blood flow in the pregnant sheep. In the present experiment we investigated the effect of antipyrine on prostaglandin metabolism. Four pregnant ewes at 104 to 127 days' gestation were infused with either 1, 4, or 15 mg of antipyrine per minute via the fetal jugular vein. The 15 mg X min-1 dose was also infused into the maternal jugular vein in a fourth experiment. Prostaglandins in the uterine vein draining the pregnant horn were measured by radioimmunoassay and antipyrine by high-performance liquid chromatography. No change in the concentrations of either 13,14-dihydro-15-keto-prostaglandin F2 alpha or 6-keto-prostaglandin F1 alpha was observed with infusion of antipyrine at 1 mg X min-1. The 4 and 15 mg X min-1 infusion rates into the fetal jugular vein induced a significant decrease (p less than 0.05) in maternal uterine vein 13,14-dihydro-15-keto-prostaglandin F2 alpha plasma concentrations. These concentrations decreased from 669.3 +/- 161.3 pg X ml-1 (mean +/- SD) before infusion to 306.5 +/- 104.0 pg X ml-1 after 3 hours of infusion at 4 mg X min-1 and from 744.2 +/- 256.8 to 105.0 +/- 24.2 pg X ml-1 at 15 mg X min-1. Significant changes in maternal uterine vein plasma 6-keto-prostaglandin F1 alpha and the 6-keto-prostaglandin F1 alpha/13,14-dihydro-15-keto-prostaglandin F1 alpha ratio occurred only at the 15 mg X min-1 infusion of antipyrine into the fetal jugular vein (p less than 0.05). Maternal uterine vein 6-keto-prostaglandin F1 alpha fell from 86.0 +/- 31.6 to 37.0 +/- 11.5 pg X ml-1 and the 6-keto-prostaglandin F1 alpha/13,14-dihydro-15-keto-prostaglandin F2 alpha ratio rose from 0.14 +/- 0.10 to 0.35 +/- 0.10. We conclude that: antipyrine at doses currently used to measure uterine and umbilical blood flows inhibits 13,14-dihydro-15-keto-prostaglandin F2 alpha production and infusion rates of antipyrine less than 1 mg X min-1 probably do not affect maternal prostaglandin metabolism. We therefore recommend that if this method is to be used for measuring blood flow, antipyrine infusion rates should be less than 1 mg X min-1.


Single fiber-in-capillary annular column for gas chromatographic separation.
A method for preparation of a stationary phase-adjustable column with in-column stationary phase-coated fused-silica fiber annular column was successfully developed. The surface of a 0.12 mm o.d. bare optical fiber was first coated with a stationary phase and then inserted into a fused-silica capillary (non-coated or coated) as an annular column for gas chromatographic study. The optical fiber and capillary were coated with polydimethylsiloxane (SE-30) and polyethylene glycol 20 M (PEG-20 M) as nonpolar and polar stationary phases, respectively. Among the investigated annular and open tubular columns, the PEG-20 M-coated fiber-in-PEG-20 M-coated capillary annular column showed the highest column efficiency with a minimum plate height of 0.35 mm and an optimum gas velocity of 25 cm/s. When a SE-30/PEG-20 M-coated fiber-in-uncoated capillary annular column was applied to separate a 9-component complex mixture, the total analysis time was 5.3 min and the column length was 12 m. By contrast, when a SE-30-coated fiber-in-PEG-20 M-coated capillary annular column was used to separate the same 9-component mixture, the analysis time was reduced to 3.5 min and the column length was shortened by half to 6m. Our results show that the stationary phase-coated fiber-in-stationary phase-coated capillary annular column is a better choice for gas chromatographic separation as it is more efficient and flexible. In addition, the proposed annular column design provides flexibility in using two or even more types of stationary phases to achieve optimal analytical separation.


Multi-species interactions among a commensal (Chaetogaster limnaei limnaei), a parasite (Schistosoma mansoni), and an aquatic snail host (Biomphalaria glabrata).
This study assessed the effects of a commensal, Chaetogaster limnaei limnaei, and a parasitic trematode, Schistosoma mansoni, on infection patterns and life-history responses in the aquatic snail Biomphalaria glabrata. Prevalence of infection was significantly higher in snails that were devoid of C. limnaei limnaei relative to those that were colonized by the commensal, indicating that the oligochaete may protect the host from trematode infection. This finding appeared to be the direct result of the commensal as opposed to indirect stimulation of the immune system, as hemocyte numbers did not differ between C. limnaei limnaei-colonized and noncolonized snails. Snail growth and reproduction were affected by the presence of C. limnaei limnaei and exposure to S. mansoni. Two-way ANOVA revealed a significant effect of both C. limnaei limnaei presence and trematode exposure on B. glabrata growth over the 5-wk study with C. limnaei limnaei-colonized and parasite-infected snails demonstrating the greatest growth. Snails exposed, but uninfected, by S. mansoni demonstrated the lowest growth regardless of commensal colonization. Chaetogaster limnaei limnaei colonization had no effect on egg production, but S. mansoni-infected snails produced significantly more eggs than individuals from other treatment groups. Survival remained over 85% in all treatment groups. The ecological implications of these results are discussed.


Does the conceptus of the viviparous lizard Barisia imbricata imbricata participates in the regulation of progesterone production and the control of luteolysis?
It is generally accepted that progesterone is necessary to maintain gestation; however, the mechanisms that control the production of this steroid remain unknown. The corpus luteum has been assigned a central role in the maintenance of gestation based on its capacity to produce progesterone. A pseudopregnancy model was performed in a viviparous lizard, Barisia imbricata imbricata, to determine whether the absence of embryos would affect the pattern of progesterone production or the corpus luteum histology. Blood samples were obtained prior to ovulation and at 8, 16, and 24 weeks after ovulation (pseudopregnant and pregnant lizards), as well as one day after parturition (pregnant lizards) or 32 weeks after ovulation (pseudopregnant lizards). The corpus luteum was surgically removed one day after blood samples were obtained. Blood aliquots from nongravid females were obtained at similar timepoints. We found a significant reduction in plasma progesterone concentrations at 24 and 32 weeks post-ovulation in pseudopregnant lizards compared with those observed at similar times in intact pregnant lizards, whereas the progesterone levels in non-gestant lizards remained significantly lower than in either pseudopregnant or pregnant lizards. Moreover, we observed that the histological appearance of the corpus luteum from pseudogestational females (obtained 24 and 32 weeks post-ovulation) differed from the corpora lutea from lizards in late gestation and intact parturient lizards. These observations suggest that the conceptus participates in the regulation of progesterone production in late gestation and also in luteolysis control.


CT angiography with cardiac MRI: non-invasive functional and anatomical assessment for the etiology in newly diagnosed heart failure.
Exclusion of ischemia is important in patients with newly diagnosed systolic heart failure (HF). We prospectively compared standard-of-care invasive catheter angiography (iCA) and echocardiography to a novel non-invasive strategy of both Coronary Computed Tomographic Angiography (CCTA) and Cardiovascular MRI (CMR) to determine the etiology of myocardial dysfunction Prospective data were collected from consecutive patients referred for iCA to investigate echocardiographically-confirmed new onset HF. CMR (1.5T GE) and dual source CCTA were performed within 2-7 days of iCA. Results were blinded and separately analyzed by expert readers. 426 coronary segments from 28 prospectively enrolled patients were analyzed by CCTA and quantitative iCA. The per-patient sensitivity and specificity of CCTA was 100% and 90%, respectively, negative predictive value (NPV) 100%, positive predictive value (PPV) 78%. Mean ejection fraction by CMR was 24%. Presence of ischemic-type LGE on CMR conferred a 67% sensitivity, 100% specificity, 90% NPV and 100% PPV. Combining CCTA with CMR conferred 100% specificity, 100% sensitivity, 100% PPV and 100% NPV for detection or exclusion of coronary disease. In patients with negative CCTA all invasive angiograms could have been avoided. In addition, two patients with no ischemic LGE by CMR had severe coronary disease on both CCTA and iCA, indicating global hibernation. This is a noteworthy finding in contrast to previous reports which suggested that absence of LGE rules out significant CAD. CCTA with CMR in newly-diagnosed HF enables non-invasive assessment of coronary artery disease, the severity and etiology of myocardial dysfunction and defines suitability for revascularization. Absence of ischemic-type LGE at CMR does not exclude CAD as a cause of LV dysfunction. A first-line strategy of functional and anatomic imaging with CMR and CCTA appears appropriate in newly diagnosed HF.


Skin metabolome reveals immune responses in yellow drum Nibea albiflora to Cryptocaryon irritans infection.
The yellow drum Nibea albiflora is less susceptible to Cryptocaryon irritans infection than is the case with other marine fishes such as Larimichthys crocea, Lateolabrax japonicus, and Pagrus major. To investigate further their resistance mechanism, we infected the N. albiflora with the C. irritans at a median lethal concentration of 2050 theronts/g fish. The skins of the infected and the uninfected fishes were sampled at 24 h and 72 h followed by an extensive analysis of metabolism. The study results revealed that there were 2694 potential metabolites. At 24 h post-infection, 12 metabolites were up-regulated and 17 were down-regulated whereas at 72 h post-infection, 22 metabolites were up-regulated and 26 were down-regulated. Pathway enrichment analysis shows that the differential enriched pathways were higher at 24 h with 22 categories and 58 subcategories (49 up, 9 down) than at 72 h whereby the differential enriched pathways were 6 categories and 8 subcategories (4 up, 4 down). In addition, the principal component analysis (PCA) plot shows that at 24 h the metabolites composition of infected group were separately clustered to uninfected group while at 72 h the metabolites composition in infected group were much closer to uninfected group. This indicated that C. irritans caused strong metabolic stress on the N. albiflora at 24 h and restoration of the dysregulated metabolic state took place at 72 h of infection. Also, at 72 h post infection a total of 17 compounds were identified as potential biomarkers. Furthermore, out of 2694 primary metabolites detected, 23 metabolites could be clearly identified and semi quantified with a known identification number and assigned into 66 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Most of the enriched KEGG pathways were mainly from metabolic pathway classes, including the metabolic pathway, biosynthesis of secondary metabolites, taurine and hypotaurine metabolism, purine metabolism, linoleic acid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis. Others were glyoxylate and dicarboxylate metabolism, glutathione metabolism, and alanine, aspartate, and glutamate metabolism. Moreover, out of the identified metabolites, only 6 metabolites were statistically differentially expressed, namely, L -glutamate (up-regulated) at 24 h was important for energy and precursor for other glutathiones and instruments of preventing oxidative injury; 15-hydroxy- eicosatetraenoic acid (15-HETE), (S)-(-)-2-Hydroxyisocaproic acid, and adenine (up-regulated) at 72 h were important for anti-inflammatory and immune responses during infection; others were delta-valerolactam and betaine which were down-regulated compared to uninfected group at 72 h, might be related to immure responses including stimulation of immune system such as production of antibodies. Our results therefore further advance our understanding on the immunological regulation of N. albiflora during immune response against infections as they indicated a strong relationship between skin metabolome and C. irritans infection.


Integrating health-related quality of life findings from randomized clinical trials into practice: an international study of oncologists' perspectives.
Although health-related quality of life (HRQL) is increasingly assessed in randomized controlled trials (RCTs), HRQL findings are not always incorporated into clinical decision making. We examined the current perspectives of oncologists on the use of HRQL findings from RCTs, and variation of these perspectives between countries and specialties. A cross-sectional e-survey of oncologist members of the NCIC Clinical Trials Group, the United Kingdom National Cancer Research Institute Clinical Studies Groups, and the Australia/New Zealand cancer clinical trials network was conducted. Respondents reported their perceptions of the usefulness of RCT HRQL outcomes for informing practice, their use of HRQL findings in practice, barriers/facilitators to this use, and preferences for HRQL data presentation in RCT publications. Chi-square tests compared responses between countries and specialties. A total of 396 oncologists participated (estimated response rate: 30%). The most frequently reported specialties were medical (46%) and radiation (37%) oncology. HRQL findings from RCTs were reported as useful (73%), but were infrequently used to guide clinical decisions with patients. Perceived barriers were lack of time (67%) and understanding (57%), and concerns about generalizability of results (68%). Identified facilitators included joint publication of HRQL/clinical outcomes (96%) and summary of clinical implications of HRQL findings in RCT publications (76%). Use of HRQL findings, perceived barriers/facilitators, and presentation preferences did not differ by country or specialty. Oncologists support HRQL findings from RCTs, but perceive important barriers to their use in clinical decision making, regardless of country or specialty. Combined, clear reporting of HRQL/clinical data may facilitate their clinical application.


The negative association between trait mindfulness and post-traumatic stress disorder: A 4.5-year prospective cohort study.
Post-traumatic stress disorder (PTSD) is a chronic, disabling condition. Our main objective is to investigate the association between trait mindfulness and PTSD over a period of 54 months. The secondary objective is to provide an exhaustive description of PTSD trajectories after the Bataclan attack. We designed a prospective cohort study of 133 subjects present in the Bataclan concert hall during the November 2015 terrorist attack in Paris, France. Data were recorded 6, 18, 30, and 54 months after the attack. The primary endpoint was evaluated using the PTSD Check List Scale. Trait mindfulness was measured by the 14-item Freiburg Mindfulness Inventory. FMI scores were consistently, significantly, and negatively associated with PCL-5 scores. Adjusted odds ratios were at 0.81 (6 months), 0.88 (18 months) 0.82 (30 months), and 0.81 (54 months). PTSD prevalence 6 months after the event was 77%; it remained at 41% after 54 months. PTSD status of subjects is fluctuating. Latent class analysis divided the cohort into 3 groups: 21% of subject who remained below PTSD threshold throughout, 30% who remained above throughout, and 49% who steadily reduced their PTSD scores over time. In our cohort, mindfulness is negatively associated with PTSD. Mindfulness programs are designed to improve global resilience and treat anxiety and mood disorders. Further research is needed to investigate if improving trait mindfulness is possible and beneficial for patients suffering from PTSD.


[Intracerebral hemorrhage in anticoagulated patients: what do we do afterwards?].
The management of antithrombotic therapy after intracerebral hemorrhage (ICH) in anticoagulated patients is not well defined. We analyzed the risks and benefits of antiplatelet therapy (AG) against the resumption of anticoagulation with vitamin K antagonists (AVK) in a series of patients. Retrospective study of ICH in anticoagulated patients. We registered demographic data, history of hypertension (HT), time of follow-up and new cerebral vascular events (ICH, stroke [IC]). We evaluated 88 patients, mean age 69±9 years, 50% men, 73% hypertensive. During the acute phase 18 patients died and the follow-up was lost in 31. Of the remaining (n=39), AVKs were resumed in 25 and changed to AG in 14. Comparing the characteristics of both groups, the anticoagulated group was younger (P=.005) and the embolic sources were more often of higher risk (P=.003). After an average follow-up of 54±31 months, the distribution of events was: IC (AVKs 8%, AG 14.3%, P=.6), ICH (AVKs 24%, AG 7.1%, P=.38), IC or ICH (AVKs 32%, AG 21.4%, P=.48) and death (AVKs 29%, AG 7.1%, P=.21). This trend of increased risk of new events in patients with AVKs was confirmed by Kaplan-Meier curves, although without statistical differences. Restarting AVK treatment after ICH in anticoagulated patients could increase the risk of new bleeding events and mortality. Prospective studies are needed to define a better and appropriate antithrombotic therapy after ICH related with anticoagulation.


Constructing and deconstructing GATA2-regulated cell fate programs to establish developmental trajectories.
Stem and progenitor cell fate transitions constitute key decision points in organismal development that enable access to a developmental path or actively preclude others. Using the hematopoietic system, we analyzed the relative importance of cell fate-promoting mechanisms versus negating fate-suppressing mechanisms to engineer progenitor cells with multilineage differentiation potential. Deletion of the murine Gata2-77 enhancer, with a human equivalent that causes leukemia, downregulates the transcription factor GATA2 and blocks progenitor differentiation into erythrocytes, megakaryocytes, basophils, and granulocytes, but not macrophages. Using multiomics and single-cell analyses, we demonstrated that the enhancer orchestrates a balance between pro- and anti-fate circuitry in single cells. By increasing GATA2 expression, the enhancer instigates a fate-promoting mechanism while abrogating an innate immunity-linked, fate-suppressing mechanism. During embryogenesis, the suppressing mechanism dominated in enhancer mutant progenitors, thus yielding progenitors with a predominant monocytic differentiation potential. Coordinating fate-promoting and -suppressing circuits therefore averts deconstruction of a multifate system into a monopotent system and maintains critical progenitor heterogeneity and functionality.


Resection of a large, ruptured, undifferentiated (embryonal) sarcoma of the liver in a child: a case report and review of the literature.
Undifferentiated (embryonal) sarcoma (UES) of the liver is a malignant hepatic neoplasm accounting for 7% of pediatric hepatic tumors. Current use of multimodal therapy, including chemotherapy and surgery, has greatly improved survival. Tumor rupture is uncommon and, prior to the adjuvant use of sarcoma based chemotherapy regimens, was thought to be poor prognostic sign. A 10-year-old girl presented with acute worsening of abdominal pain while being worked up for liver mass. At surgery, she was found to have a ruptured, 20 x 15 x 5 centimeter (cm) UES, the largest reported ruptured UES to be resected primarily. The size and position of her tumor required very aggressive surgery for complete resection. She subsequently received adjuvant chemotherapy and radiation. Twenty-four months following surgery she is doing well with no evidence of disease. Despite tumor rupture, complete tumor resection gives the patient the best chance of long-term survival. Aggressive surgery is warranted if the tumor can be completely resected.


Biomarkers of diabetes-associated oxidative stress and antioxidant status in young diabetic patients with or without subclinical complications.
The aims of the study were to ascertain the potential role of oxidative stress in the onset of disease-related pathophysiological complications in young type 1 diabetes patients. Indicative parameters of lipoperoxidation, protein oxidation, and changes in antioxidant defense system status were measured in blood samples from 26 young diabetic patients with recently diagnosed (< 6 months) microangiopathy (+DC), 28 diabetic patients without complications (-DC), and 40 healthy age-matched controls (CR). Both diabetic groups presented similar fructosamine and glycated hemoglobin (HbA1c) values. Results showed erythrocyte glutathione peroxidase activity, glutathione content, and plasma beta-carotene to be significantly lower in diabetic patients compared with control subjects, but with no significant differences between -DC and +DC groups. Antioxidant enzyme superoxide dismutase activity was significantly higher in the erythrocytes of diabetic patients independently of the presence of microvascular complications. However, the plasma alpha-tocopherol/total lipids ratio was significantly diminished in +DC group compared with -DC (p =.008). Lipid peroxidation indices measured in plasma included malondialdehyde, lipid hydroperoxides, and lipoperoxides, which were significantly elevated in our diabetic patients regardless of the presence of complications. Evidence of oxidative damage to proteins was shown both through the quantification of plasma protein carbonyl levels, which were significantly higher in -DC (0.61 +/- 0.09 mmol/mg prot), and higher still in the +DC patients (0.75 +/- 0.09 mmol/mg prot) compared with those of controls (0.32 +/- 0.03 mmol/mg prot; p <.01) and immunoblot analysis of protein-bound carbonyls. Additionally, a marked increase in protein oxidation was observed in +DC patients through assessment of advanced oxidation protein products (AOPP) considered to be an oxidized albumin index; AOPP values were significantly higher in +DC than in -DC patients (p <.01) and CR (p <.0001). These results point to oxidatively modified proteins as a differential factor possibly related to the pathogenesis of diabetic complications.


A prospective multicenter study on cutaneous reactions reported after Sinopharm COVID-19 vaccination.
The new coronavirus COVID-19 pandemic has had an unprecedented impact on global health and economic growth. A widely used vaccine is the weakened inactivated severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) virus (Sinopharm). Following major SARS-CoV-2 vaccination campaigns, cutaneous symptoms are on the rise. This study is a prospective observational study evaluating cutaneous reactions and time of recovery after Sinopharm vaccination. The cases involved were over the age of 18. The data were anonymized. On the registry's vaccine section, we tracked vaccination dates, skin reactions, and recovery times. All respondents who reported only a cutaneous reaction to the first vaccination dose received a follow-up contact asking about a second vaccination dose cutaneous reaction. The study included 4560 cases. The mean age of all studied cases was 41.2 ± 6.1 years. There were dermatologic complications in 1190 patients (26.1%). There was induration at the injection site in 495 patients (10.9%), urticaria in 210 patients (4.6%), morbilliform eruption in 375 patients (8.2%), flare of skin site in 105 patients (2.3%), and angioedema in 105 patients (2.3%). The mean recovery days in all studied patients were 2.92 ± 0.94 days with a minimum recovery period of 2 days and a maximum of 7 days. Because Sinopharm's cutaneous reactions are frequently mild and self-limiting, vaccination should not be discouraged based on these findings. If the first vaccine dose creates a cutaneous reaction, there is no need to skip the second dose.


Dietary conjugated linoleic acid isomers change the unsaturation degree of hepatic fatty acids in neutral lipids but not in polar lipids.
The fatty acid composition of phospholipids plays a key role in the structural and functional properties of cellular membrane. In this study, it was hypothesized that conjugated linoleic acid (CLA) isomer supplementation changes the unsaturation degree of the fatty acids of neutral lipids (NLs) but not those of polar lipids (PLs). Thus, the main goal was to determine the pattern of fatty acid incorporation into hepatic PL and NL fractions. Wistar male rats were fed cis(c)9,trans(t)11 and t10,c12 CLA isomers, separately or as a mixture. Whereas the t10,c12 isomer incorporation in the PL fraction was similar when supplemented either individually or as a mixture, the c9,t11 isomer reached the highest values of incorporation when combined with t10,c12. In the PL fraction, the linoleic acid did not change; but the arachidonic acid decreased, especially in the rats given the mixture. Also in this fraction, the t10,c12 isomer, either separately or as a mixture, decreased the amounts of n-6 long-chain (LC) polyunsaturated fatty acids (PUFA) and increased those of the n-3 LC PUFA relative to the control. In the NL fraction, linoleic acid incorporation followed the diet composition, whereas the arachidonic acid was similar among treatments. Facing CLA isomer supplementation, the present study suggests that fatty acid incorporation into phospholipids, through the balance between n-6 and n-3 LC PUFA, is dependent upon maintaining the unsaturation degree of cellular membrane.


Landscape pattern change and its correlation with influencing factors in semiarid areas, northwestern China.
The West Liaohe Plain (WLP) is a typical crop-pastoral ecotone of the semiarid area in Northwestern, China. Land use/cover change (LUCC) of the WLP might endanger this ecosystem, triggering long-lasting environmental concerns. LUCC data for China (1980-2020) and hydrometeorological data were analyzed to reveal factors contributing to change and explore sustainable development opportunities. The results show that characteristics of the main land-use types in the WLP have changed significantly, especially cultivated land area, which increased by 15.2% and 6.79% during the periods 1980-1995 and 2000-2020, respectively. Response relationships were observed due to natural (precipitation, temperature, and runoff) and anthropogenic (economy) factors and LUCC. Between 2000 and 2020, the impact of anthropogenic factors on cultivated land was stronger than on grassland at the class and landscape level, using the landscape indices which were selected, including percent of landscape (PLAND), number of patches (NP), largest patch index (LPI), and Shannon's evenness index (SHEI). Expansion of cultivated land from 1990 to 1995 was not only related to anthropogenic factors but also to hydrological & climatic factors. The results of this study have the potential to influence sustainable land resource development.


Adsorption mechanism-based screening of cyclodextrin polymers for adsorption and separation of pesticides from water.
A rational screening of cyclodextrin-based polymer (CDP), in terms of the relationship between adsorption potential and adsorbent-adsorbate, was investigated to adsorb and separate pesticides from water. Seven spherical porous CDPs were prepared with onefold or composite cyclodextrin(s) as complex and epichlorohydrin as cross-linking reagent. The adsorption kinetics and isotherms of the polymers toward a mixture of ten distinct pesticides clearly demonstrate that the adsorbents with a homogeneous open network structure can absorb pesticides via multiple adsorption interactions such as CD inclusion, loading into swelling water and physical adsorption on network. The multivariate regression analysis distinguishes the quantitative contributions of polymer properties to its adsorption potential, among which CD content, swelling capacity and pore size appear to be major influencing factors. Consequently, a facile mixture of three CDPs (i.e., β-CDP, RM-CDP and HP-CDP) was screened to obtain above prerequisite properties. The multiplex polymer could superiorly separate the pesticides at environmentally relevant levels from water.


Limitations of current practices in detection of bacterially contaminated blood products associated with suspected septic transfusion reactions.
In the setting of suspected septic transfusion reactions, bacterial culture of both the transfused patient and the residual blood component is recommended. Primary bacterial contamination can occur at the time of component collection. Clinically insignificant "secondary contamination" can occur during post-transfusion component discard, retrieval for culture, or manipulation of the bag at the time of culture sampling. This retrospective, multi-center study analyzes positive residual component culture results and companion patient blood cultures from 15 hospitals, 1 blood center, and all cultured transfusion reactions within the province of Quebec, Canada, over a 5-year period. Imputability was assigned as "definite" (concordant growth), "possible" (discordant growth or lack of growth in patient culture), or "unable to assess" (patient not cultured). There were 373 positive component cultures from 360 unique transfusion reactions, with 276 (76.7%) companion patient blood cultures performed, of which 10 (2.8%) yielded the pathogen detected in the positive component. Of these 10 definite pathogens, 7 (2 Staphylococcus aureus, 3 other staphylococci, and 1 Streptococcus pyogenes and 1 Bacillus sp.) were associated with platelet and 3 (Aeromonas veronii, Staphylococcus epidermidis, and Enterococcus faecalis) with RBC transfusions. RBC and plasma components comprised 70% of positive component cultures. The process of performing residual component culture is vulnerable to secondary contamination. The significance of microorganisms recovered from component culture cannot be interpreted in isolation. In the context of low prevalence of primary contamination of blood components, the positive predictive value of a positive component culture result is very low.


Rapid identification, isolation, and evaluation on anti-neuroinflammatory activity of limonoids derivatives from the root bark of Dictamnus dasycarpus.
A total of 49 limonoids derivatives were rapidly identified by UNIFI software and three new limonoids derivatives, named dasycarinone (1, DAS), isodictamdiol C (2) and dasycarinone A (3), along with nineteen known compounds, were isolated from the root bark of Dictamnus dasycarpus, named as "Baixianpi" in Chinese. Their structures were elucidated on the basis of spectroscopic data (UV, IR, HR-ESI-MS, NMR, CD spectra and OR). All the compounds were tested for anti-inflammatory activities by suppressing the nitric oxide (NO) production in lipopolysaccharide (LPS) induced BV-2 cells. DAS exhibited a strong anti-inflammatory activity with IC50 value of 1.8 μM. Nuclear Factor kappa B (NF-κB) luciferase assay and enzyme-linked immune sorbent assay indicated that DAS can suppress the release of inflammatory cytokines such as Tumor Necrosis Factor α (TNF-α), interleukin 6 (IL-6) via inactivating NF-κB signaling pathways. Moreover, we found that anti-inflammatory activities of obacunone-class are better than those of limonin-class by analyzing structure-activity relationship. Our results suggested that obacunone derivatives play an important role on anti-inflammation of Baixianpi. As a representative among them, DAS showed a strong anti-inflammatory activity via suppressing NF-κB signaling pathways.


Visual Dysfunction in Multiple Sclerosis and its Animal Model, Experimental Autoimmune Encephalomyelitis: a Review.
Visual disabilities in central nervous system autoimmune diseases such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are important symptoms. Past studies have focused on neuro-inflammatory changes and demyelination in the white matter of the brain and spinal cord. In MS, neuro-inflammatory lesions have been diagnosed in the visual pathway; the lesions may perturb visual function. Similarly, neuropathological changes in the retina and optic nerves have been found in animals with chronic EAE. Although the retina and optic nerves are immunologically privileged sites via the blood-retina barrier and blood-brain barrier, respectively, inflammation can occur via other routes, such as the uvea (e.g., iris and choroid) and cerebrospinal fluid in the meninges. This review primarily addresses the direct involvement of the blood-retina barrier and the blood-brain barrier in the development of retinitis and optic neuritis in EAE models. Additional routes, including pro-inflammatory mediator-filled choroidal and subarachnoid spaces, are also discussed with respect to their roles in EAE-induced visual disability and as analogues of MS in humans.


In Vivo Expression of NUP93 and Its Alteration by NUP93 Mutations Causing Focal Segmental Glomerulosclerosis.
Mutations in genes encoding nucleoporins (NUPs; components of nuclear pore complexes [NPCs]), such as NUP93, have been reported to cause steroid-resistant nephrotic syndrome (SRNS) or focal segmental glomerulosclerosis (FSGS), which often progresses to end-stage renal disease (ESRD) in childhood. The expression of NUP93 in renal or extrarenal tissues, and the mechanism by which NUP93 mutations cause this renal phenotype, remain unclear. The expression of NUP93 in normal control kidney and in a patient with FSGS carrying NUP93 mutations was examined by immunofluorescence analysis. The expression of NUP93 in blood cells was analyzed by Western blot analysis. Immunofluorescence analysis detected NUP93 expression in nuclei of all glomerular and tubulointerstitial cells in human kidneys. Whole-exome sequencing identified a compound heterozygous NUP93 mutation comprising a novel missense mutation p.Arg525Trp, and a previously reported mutation, p.Tyr629Cys, in a patient with FSGS that developed ESRD at the age of 6 years. In the patient's kidney, the intensity of NUP93 immunofluorescence was significantly decreased in the nuclei of both glomerular and extraglomerular cells. The expression of CD2-associated protein (CD2AP) and nephrin in the patient's podocytes was relatively intact. The amount of NUP93 protein was not significantly altered in the peripheral blood mononuclear cells of the patient. NUP93 is expressed in the nuclei of all the cell types of the human kidney. Altered NUP93 expression in glomerular cells as well as extraglomerular cells by NUP93 mutations may underlie the pathogenic mechanism of SRNS or FSGS.


Single and dual cyclodextrins systems for the enantiomeric and diastereoisomeric separations of structurally related dihydropyridone analogues.
CD capillary electrophoresis methods were developed for complete enantiomeric and diastereoisomeric separations of a series of ten dihydropyridone analogues, of which eight were neutral, one was anionic, and one was cationic. Ten different systems comprising one or two CDs were found to successfully separate the isomers thanks to a screening approach. Among the tested CDs, highly sulfated-γ-CD (HS-γ-CD), either in a single or in a dual system, in a phosphate buffer using capillaries dynamically coated with polyethylene oxide, and SBE-β-CD, either in a single or in a dual system, in a borate buffer using uncoated capillaries, were the most selective selectors. The effects of different parameters such as the nature and concentration of the CDs, nature and concentration of the buffer, and voltage were examined. The precision and LODs and limits of quantification were evaluated for the optimized methods.


Myxoid leiomyosarcoma of the gizzard in a broiler chicken.
A leiomyosarcoma was found in the gizzard of a 57-day-old female broiler chicken weighing 1.8 kg. Grossly, the tumor mass, 13.0 x 8.5 x 10.0 cm, enveloped the gizzard and had a gelatinous appearance due to the rich production of mucin. Miliary metastatic tumors were noted in the liver. Histopathologically, there was marked production of mucus throughout the tumor tissue, and densely or loosely arranged long spindle-shaped leiomyosarcoma cells proliferated. The tumor cells had a low rate of mitosis, showed slight cellular atypia, and, immunohistochemically, were positive for actin, alpha-smooth muscle actin, and desmin. Electron microscopically, various amounts of microfibrils with focal densities, dense patches, and basal plates were observed.