Developmental changes of the GABA-immunoreactive fibers in the lamprey spinal cord.
The changes in distribution and number of GABA immunoreactive (GABA-ir) fibers from postembryonic stages to adulthood in the lamprey spinal cord white matter were studied by using immunocytochemical techniques. From prolarvae to adult spawning animals there was an increase of the number of GABA-ir fibers. Three phases can be distinguished: (a) from prolarvae to middle size larvae (around 50 mm in body length) an increase in the number of GABA-ir fibers per section is observed. Furthermore, an adult-like pattern of GABA-ir fibers distribution is established during this phase. (b) Then, the number of GABA-ir fibers remains stable until metamorphosis, the end of the larval period. (c) Finally, in young postmetamorphic and adult animals the number of GABA-ir fibers is higher than in larvae. These observations, joined to the changes previously reported in the GABA-ir neurons, indicate that at least parts of the GABA inhibitory component of the spinal locomotor network is reorganized during the lamprey life cycle and it may indicate different inhibitory requirements in the locomotor network.


Changes in cardiac rhythm in children treated with dopamine.
We reviewed the charts of 31 children receiving dopamine to document possible changes in cardiac rhythm associated with dopamine infusion. Six of these developed a dysrhythmia while on dopamine. All six were receiving dosages greater than 10 microgram/kg/min; in five of the six patients the infusion rate varied from 10-20 microgram/kg/min. Of the remaining 25 patients, 14 had preexisting dysrhythmias of nonventricular origin. Two of these 14 patients converted to sinus rhythm while on dopamine. Eleven patients who were in preexisting sinus rhythm had no rhythm changes on dopamine. Based on the results of this study, we recommend that dopamine should be used cautiously in children in the dosage range between 10-20 microgram/kg/min.


An exploration of the use of visually appealing contexts in a pain management program.
Pleasant pictures can help to reduce stress, promote positive feelings, and even facilitate recovery from diseases. Visual stimulation is an approach of distraction that can effectively reduce pain thresholds and increase pain tolerances. The number of older adults who suffer from pain has increased due to age-related diseases. Technology is increasingly being applied to the management of acute pain. The pain situation among older people was explored in this study, and a visually appealing pain management program was designed with the participants' experiences in mind. This was a descriptive observational study. Participants were recruited from local nursing homes. A total of 165 older adults joined the study. The mean age of the participants was 85.6. More female than male participants experienced pain and the intensity of their pain was significantly greater. The results showed no significant differences in pain interferences between males and females. The participants stated that photographs of family members, homes, and natural scenery made them feel relaxed and happy, and reminded them of past happy times. They preferred to view those visually appealing pictures using digital devices (iPad/iPhone) to seeing hard copy versions. A digital-based pain management program using visually appealing contexts for older adults can be implemented. The patients' experiences were collected and will be considered when developing a future program.


MRI-based peritumoral radiomics analysis for preoperative prediction of lymph node metastasis in early-stage cervical cancer: A multi-center study.
To evaluate intra- and preitumoral radiomics on the contrast-enhanced T1-weighted (CE-T1) and T2-weighted (T2W) MRI for predicting the LNM, and develop a nomogram for potential clinical uses. We enrolled 169 cervical cancer cases who underwent CE-T1 and T2W MR scans from two hospitals between Dec. 2015 and Sep. 2021. Intra- and peritumoral features were extracted separately and selected by the least absolute shrinkage and selection operator (LASSO) regression. Radiomics signatures were built using the selected features from different regions. Clinical parameters were evaluated by statistical analysis. The nomogram was developed combining the multi-regional radiomics signature and the most predictive clinical parameters. Five radiomics features were finally selected from the peritumoral regions with 1 and 3 mm distances in the CE-T1 and T2W MRI, respectively. The nomogram incorporating multi-regional combined radiomics signature, MR-reported LN status and tumor diameter achieved the highest AUCs in the training (nomogram vs. combined radiomics signature vs. clinical model, 0.891 vs. 0.830 vs. 0.812), internal validation (nomogram vs. combined radiomics signature vs. clinical model, 0.863 vs. 0.853 vs. 0.816) and external validation (nomogram vs. combined radiomics signature vs. clinical model, 0.804 vs. 0.701 vs. 0.787) cohort. DCA suggested good clinical usefulness of our developed models. The current work suggested clinical potential for intra- and peritumoral radiomics with multi-modal MRI for preoperative predicting LNM.


Environmentally relevant cadmium concentrations affect development and induce apoptosis of Paracentrotus lividus larvae cultured in vitro.
Sea urchin embryos and larvae represent suitable model systems on where to investigate the effects of heavy metals on development and cell viability. Here, we tested the toxic effects of low (10(-12 )M), medium (10(-9 )M), and high (10(-6 )M) cadmium chloride concentrations, mimicking unpolluted, moderately and highly polluted seawaters, respectively, on Paracentrotus lividus sea urchins offspring. Larvae were continuously treated from fertilization and inspected at time intervals comprised between 10 and 30 days of development. Delays and/or morphological abnormalities were firstly evident in larvae treated for 15 days with high cadmium (10(-6 )M) and for 25 days with medium cadmium (10(-9 )M). Major defects consisted in the reduction and lack of arms and skeleton elongation. No obvious differences with respect to controls were observed in embryos/larvae exposed to low cadmium (10(-12) M), even after 30 days of exposure. Using in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay (TUNEL) assay on larvae whole mounts, we detected apoptosis after 10 days of treatment with 10(-6) and 10(-9) M CdCl(2,) when no morphological abnormalities were recognizable yet. Supernumerary apoptotic cells were found in arm buds, ciliary bands, and apex. In conclusion, echinoderm embryos and larvae represent candidates of choice for the study of stress and defense mechanisms activated by cadmium exposure.


Taurine: effect on myocardial relaxation.
1. The effects of taurine on cardiac inotropic state and relaxation were studied in the isolated rabbit heart using solutions containing three concentrations of calcium: 0.7, 1.8 and 3.0 mmol/l. 2. Increases in Ca2+ caused increases in inotropic indices, but had no effect on rate constant of relaxation. 3. Taurine had a positive inotropic effect at Ca2+ = 0.7 mmol/l, an equivocal effect at Ca2+ = 1.8 mmol/l and a negative inotropic effect at Ca2+ = 3.0 mmol/l. 4. Taurine had no effect on the rate constant of relaxation at any Ca2+ concentration. 5. Taurine modulates the positive inotropic effect of Ca2+ but neither taurine nor Ca2+ affect the rate constant of relaxation.


Modeling of selenite toxicity to wheat root elongation using biotic ligand model: Considering the effects of pH and phosphate anion.
It has not been well understood that the binding affinity and potential toxicity of different chemical forms of selenite (Se(IV)), which are predominant forms of selenium with plant availability. The influences of pH and major anions on Se(IV) toxicity to wheat root elongation were determined in solutions and modeled based on the biotic ligand model (BLM) and free ion activity model (FIAM) concepts. Results showed that EC50[Se(IV)]T values increased from 164 to 273 μM as the pH raised from 4.5 to 8.0, indicating the increase of pH induced weakened Se(IV) toxicity. The EC50{SeO32-} values increased from 0.019 to 71.3 μM while the EC50{H2SeO3} values sharply decreased from 2.08 μM to 0.760 nM with the pH increasing from 4.5 to 8.0. The effect of pH on Se(IV) toxicity could be explained by the changes of Se(IV) species in different pH solutions as H2SeO3, HSeO3- and SeO32- were differently toxic to wheat root elongation. The toxicity of Se(IV) decreased with increasing H2PO4- activity but not for SO42-, NO3- and Cl- activities, indicating that only H2PO4- had a competitive effect with Se(IV) on the binding sites. A site-specific BLM was developed to count in effects of pH and H2PO4-, and stability constants of H2SeO3, HSeO3-, SeO32- and H2PO4- to the binding sites were obtained: log [Formula: see text] = 4.96, log [Formula: see text] = 3.47, log [Formula: see text] = 2.56 and log [Formula: see text] = 2.00. Results implied that BLM performed much better than FIAM in the wheat root elongation prediction when coupling toxic species H2SeO3, HSeO3-, SeO32-, and the competitions of H2PO4- for the binding sites while developing the Se(IV)-BLM.


The transcriptional coactivator Bob1 promotes the development of follicular T helper cells via Bcl6.
Follicular T helper (Tfh) cells are key regulators of the germinal center reaction and long-term humoral immunity. Tfh cell differentiation requires the sustained expression of the transcriptional repressor Bcl6; however, its regulation in CD4(+)T cells is incompletely understood. Here, we report that the transcriptional coactivator Bob1, encoded by thePou2af1gene, promotes Bcl6 expression and Tfh cell development. We found that Bob1 together with the octamer transcription factors Oct1/Oct2 can directly bind to and transactivate theBcl6andBtlapromoters. Mixed bone marrow chimeras revealed that Bob1 is required for the expression of normal levels of Bcl6 andBTLA, thereby controlling the pool size and composition of the Tfh compartment in a T cell-intrinsic manner. Our data indicate that T cell-expressed Bob1 is directly involved in Tfh cell differentiation and required for mounting normal T cell-dependent B-cell responses.


Chlorpyrifos: pharmacokinetics in human volunteers.
The kinetics of chlorpyrifos, an organophosphorothioate insecticide, and its principal metabolite, 3,5,6-trichloro-2-pyridinol (3,5,6-TCP), were investigated in six healthy male volunteers given a single 0.5 mg/kg po and, 2 or more weeks later, a 0.5 or 5.0 mg/kg dermal dose of chlorpyrifos. No signs or symptoms of toxicity or changes in erythrocyte cholinesterase were observed. Plasma cholinesterase was depressed to 15% of predose levels by the 0.5 mg/kg po dose but was essentially unchanged following the 5.0 mg/kg dermal dose. Blood chlorpyrifos concentrations were extremely low (less than 30 ng/ml), and no unchanged chlorpyrifos was found in the urine following either route of administration. Mean blood 3,5,6-TCP concentrations peaked at 0.93 micrograms/ml 6 hr after ingestion of the oral dose and at 0.063 micrograms/ml 24 hr after the 5.0 mg/kg dermal dose. 3,5,6-TCP was cleared from the blood and eliminated in the urine with a half-life of 27 hr following both the po and dermal doses. An average of 70% of the po dose but less than 3% of the dermal dose was excreted in the urine as 3,5,6-TCP; thus only a small fraction of the dermally applied chlorpyrifos was absorbed. Chlorpyrifos and its principal metabolite were rapidly eliminated and therefore have a low potential to accumulate in man on repeated exposures. Based on these data, blood and/or urinary 3,5,6-TCP concentrations could be used to quantify the amount of chlorpyrifos absorbed under actual use conditions.


A Personalized Risk Model for Azacitidine Outcome in Myelodysplastic Syndrome and Other Myeloid Neoplasms Identified by Machine Learning Model Utilizing Real-World Data.
Azacitidine is an approved therapy for higher-risk myelodysplastic syndrome (MDS). However, only 30-40% patients respond to azacitidine, and the responses may take up to six cycles to become evident. Delayed responses and the myelosuppressive effects of azacitidine make it challenging to predict which patients will benefit. This is further compounded by a lack of uniform prognostic tools to identify patients at risk of early treatment failure. Hence, we performed a retrospective analysis of 273 consecutive azacytidine-treated patients. The median overall survival was 16.25 months with only 9% alive at 5 years. By using pre-treatment variables incorporated into a random forest machine learning model, we successfully identified those patients unlikely to benefit from azacytidine upfront (7.99 vs. 22.8 months, p < 0.0001). This model also identified those who required significantly more hospitalizations and transfusion support. Notably, it accurately predicted survival outcomes, outperforming the existing prognostic scoring system. By integrating somatic mutations, we further refined the model and identified three distinct risk groups with significant differences in survival (5.6 vs. 10.5 vs. 43.5 months, p < 0.0001). These real-world findings emphasize the urgent need for personalized prediction tools tailored to hypomethylating agents, reducing unnecessary complications and resource utilization in MDS treatment.


Influence of phenanthrene on cadmium toxicity to soil enzymes and microbial growth.
Many contaminated sites contain a variety of toxicants. Risk assessment and the development of soil quality criteria therefore require information on the interaction among toxicants. Interactions between heavy metals are relatively well studied, but little is known about those between heavy metals and polycyclic aromatic hydrocarbons (PAHs). 0.1 mg/kg dry soil phenanthrene alone or phenanthrene plus 10 mg/kg cadmium (Cd) were added to soil to determine the influence of phenanthrene on Cd toxicity to soil enzymes (invertase, urease, dehydrogenase and phosphatase) and microorganisms (fungi, bacteria and actinomycete) in paddy soil. 0.1 mg/kg phenanthrene did not reduce the number of microorganisms. However, the addition of phenanthrene to soil with Cd enhanced the Cd toxicity to soil enzymes and microorganisms. This deleterious effect was seen to mainly affect the growth of fungi and the activity of invertase, urease and dehydrogenase. The order of combined inhibition of Cd and phenanthrene was fungi>bacteria>actinomycete. The presence of phenanthrene might enhance the toxicity of Cd to soil microorganisms. Phenanthrene can easily be used by the soil actinomycetes as a source of carbon and energy and the finding may be supportive to the development of bioremediation techniques.


Guinea pig apolipoprotein D RNA diversity, and developmental and gestational modulation of mRNA levels.
We have isolated and characterized two molecular types of guinea pig (GP) apolipoprotein D (apoD) cDNA. The sequences of cDNA clones GP APO D-20 and -38 are 100 % homologous in their putative exons 2-5, as determined by analogy within human apoD gene, but they differ totally in their putative exon 1. RNase protection assays showed the presence of both apoD RNA types 20 and 38 in cauda epididymis. Northern blot analysis revealed four polyadenylated apoD bands at 3.2, 2.7, 1.7, and 1.0 kb. Types 20 and 38 specific probes hybridized with the major 1-kb mRNA and two of the three other minor RNA transcripts, respectively. Southern blot analysis revealed that the guinea pig genome probably contains one apoD gene. Our data also demonstrated that the cauda epididymis and fallopian tubes had an apoD mRNA concentration 100-fold higher than the liver, suggesting that the apoD gene expression could be associated with the presence of steroids. The levels of the 1-kb mRNA increased in the fallopian tubes and ovaries during gestation and were lower in fetal reproductive tissues and liver than in mature animals. No positive correlation was found between apoD and 3 beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase (3 beta-HSD) mRNA levels in these tissues, thus suggesting that high amounts of apoD mRNA are not necessarily associated with in situ progesterone synthesis. Taken together, our results indicate that both the guinea pig epididymis and fallopian tubes are excellent models to study the local role of apoD in steroid target tissues.


Impact of First Line Antiangiogenic Therapy Duration on Nivolumab Outcome in Metastatic Renal Cell Carcinoma Patients Treated in the GETUG-AFU 26 NIVOREN.
In metastatic renal clear cell carcinoma (ccRCC), vascular endothelial growth factor receptor (VEGFR) and immune checkpoint are 2 main therapeutic targets. We investigated the impact of duration exposure to antiangiogenic on immunotherapy clinical outcomes in metastatic ccRCC. Patients from NIVOREN trial who received nivolumab after only 1 prior antiangiogenic therapy were included. Response rate, clinical benefit, progression free survival (PFS) and overall survival (OS) were prospectively analyzed depending on the duration of the first line (< 6 months, ≥6 months) and exploratory in patients with long first line exposure (≥18 months). The circulating levels of 8 plasma proteins and cytokines at baseline were collected and compared according to first line antiangiogenic duration. Among 354 patients, 127 (36%) and 227 (64%) patients had received first line antiangiogenic for < 6months and ≥ 6months respectively. Respective duration of first line therapy was not associated with objective response to nivolumab (20.5% vs. 23.9%, P = .50), or PFS (HR 0.92; P = .421). Median OS was respectively 16.6 and 31.3 months in the <6 and ≥6 months subgroups respectively. Adjusted on international metastatic renal cell carcinoma database consortium risk, age and metastatic site, OS was longer in patients with longer treatment duration in the first line setting (HR 0.73; P = .017). Duration of first line VEGFR TKI was independent from circulating levels of 8 proteins and cytokines at nivolumab baseline. Nivolumab activity in second line is independent from first-line duration of VEGFR TKI. However, first line VEGFR TKI duration ≥ 6 months is associated with longer OS.


Transoperative glycemia in pets: validating old ones, and presenting lip mucosa as new sampling site.
The aim of our study was to investigate the viability and validity of blood sampling from the upper lip mucosa in healthy dogs and cats for monitoring transoperative glycemia and compare the results with those obtained from samples taken from previously described blood sampling sites for determination of glycemia using a glucose meter. Blood glucose (BG) levels were determined in samples taken from the upper lip mucosa of 24 dogs and 31 cats undergoing neutering or spaying surgeries. These values were compared to those of samples obtained from other sites previously described for capillary blood glucose monitoring (marginal ear vein, carpal pad in dogs, metacarpal pad in cats) using a glucose meter. Additionally, BG from peripheral venous blood was determined using a glucose meter, and the gold standard enzymatic colorimetric assay. The clinical reliability of BG values taken from lip mucosa and from all the other BG values measured by the glucose meter was evaluated using the error grid analysis modified by Parkes et al (2000). The upper lip mucosa was an easily accessible site for the obtainment of appropriate blood samples, and glucose levels read in these samples correlated positively with glycemic values read in blood samples from all other sites in dogs and cats. All BG made using glucose meters taken from all sites were within the clinically acceptable range when compared with enzymatic colorimetric assay (gold standard), and were analytically accurate according to the error grid (zones A and B). All blood sampling sites described in this work can be used to assess transoperative glycemia. The upper lip mucosa is a viable blood sampling site for precise monitoring of transoperative glycemia in healthy dogs and cats and shows promise for alternative blood glucose monitoring.


Positive correlation between snoring and dyslipidemia in adults: results from NHANES.
A few studies have shown that snoring, in certain populations, is associated with dyslipidemia. However, there are currently no large-scale national studies available that explore this association. Thus, for further clarification, studies using a large sample of the general population need to be conducted. This study aimed to explore this association using the National Health and Nutrition Examination Survey (NHANES) database. A cross-sectional survey was conducted using data from the NHANES database; 2005 to 2008 and 2015 to 2018 datasets were used (weighted to be representative of United States adults aged ≥ 20 years). Information on snoring status, lipid levels, and confounding factors were included. Logistic regression of the generalized linear model was used to analyze the relationship between snoring and dyslipidemia, and hierarchical analysis, interaction analysis, and sensitivity analysis were used to explore the stability of the results. Data from 28,687 participants were analyzed, and 67% of the participants had some degree of snoring. The fully adjusted multivariate logistic regression results demonstrated that snoring frequency was significantly positively associated with dyslipidemia (P < 0.001 for linear trend). Adjusted odds ratios (aORs) of dyslipidemia among those who snored rarely, occasionally, and frequently were 1.1 (95% confidence interval [CI], 1.02-1.18), 1.23 (95% CI, 1.10-1.38), and 1.43 (95% CI, 1.29-1.58), respectively, compared with that among those who never snored. In addition, age and snoring frequency showed a correlation (P = 0.02). Sensitivity analysis demonstrated that frequent snoring was significantly associated with lipid levels (all P ≤ 0.01 for linear trend), including increased low-density lipoprotein cholesterol (LDL-C) (β = 0.09 mmol/L; 95% CI, 0.02-0.16), triglyceride (TG) (β = 0.18 mmol/L; 95% CI, 0.10-0.26), total cholesterol (TC) (β = 0.11 mmol/L; 95% CI, 0.05-0.16), and decreased high-density lipoprotein cholesterol (HDL-C) (β=-0.04 mmol/L; 95% CI, -0.06--0.03). A statistically significant positive association was identified between sleep snoring and dyslipidemia. It was suggested that sleep snoring interventions may reduce the risk of dyslipidemia.


Impact of type of thrombolytic agent on in-hospital outcomes in ST-segment elevation myocardial infarction patients in the Middle East.
Little is known about the impact of thrombolytic agents on in-hospital outcomes in the Middle East. The objective of this study was to evaluate the impact of thrombolytic agents on in-hospital outcomes in ST-segment elevation myocardial infarction (STEMI) patients in six Middle Eastern countries. Gulf Registry of Acute Coronary Events was a prospective, multinational, multicentre, observational survey of consecutive acute coronary syndrome patients admitted to 65 hospitals in 2006 and 2007. Out of 1,765 STEMI patients admitted to hospitals within 12 h of symptoms onset, 25, 43, and 30% were treated with streptokinase, reteplase, and tenecteplase, respectively. Median age of the study cohort was 50 (45-59) years and majority were males (89%). The overall median symptom onset-to-presentation and median door-to-needle times were 130 min (65-240) and 45 min (30-75), respectively. Streptokinase patients had worse GRACE risk scores compared to patients who received fibrin specific thrombolytics. Academic hospitals and cardiologists as admitting physicians were associated with the use of fibrin specific thrombolytics. After significant covariate adjustment, both reteplase [odds ratio (OR), 0.38; 95% CI: 0.18-0.79; P = 0.009] and tenecteplase (OR, 0.30; 95% CI: 0.12-0.77; P = 0.012) were associated with lower all-cause in-hospital mortality compared with streptokinase. No significant differences in other in-hospital outcomes were noted between the thrombolytic agents. In conclusion, in light of the study's limitations, fibrin specific agents, reteplase and tenecteplase, were associated with lower all-cause in-hospital mortality compared to the non-specific fibrin agent, streptokinase. However, the type of thrombolytic agent used did not influence other in-hospital outcomes.


The individuality paradigm: Automated longitudinal activity tracking of large cohorts of genetically identical mice in an enriched environment.
Personalized medicine intensifies interest in experimental paradigms that delineate sources of phenotypic variation. The paradigm of environmental enrichment allows for comparisons among differently housed laboratory rodents to unravel environmental effects on brain plasticity and related phenotypes. We have developed a new longitudinal variant of this paradigm, which allows to investigate the emergence of individuality, the divergence of individual behavioral trajectories under a constant genetic background and in a shared environment. We here describe this novel method, the "Individuality Paradigm," which allows to investigate mechanisms that drive individuality. Various aspects of individual activity are tracked over time to identify the contribution of the non-shared environment, that is the extent to which the experience of an environment differs between individual members of a population. We describe the design of this paradigm in detail, lay out its scientific potential beyond the published studies and discuss how it differs from other approaches to study individuality. The custom-built cage system, commercially marketed as "ColonyRack", allows mice to roam freely between 70 cages through connector tubes equipped with ring antennas that detect each animal's ID from an RFID transponder implanted in the animal's neck. The system has a total floor area of 2.74 m2 and its spatial resolution corresponds to the size of the individual cages. Spatiotemporally resolved antenna contacts yield longitudinal measures of individual behavior, including the powerful measure of roaming entropy (RE). The Individuality Paradigm provides a rodent model of the making of individuality and the impact of the 'non-shared' environment on life-course development.


What Is the Comparative Efficacy of Surgical, Endoscopic, Transanal Resection, and Radiotherapy Modalities in the Treatment of Rectal Cancer?
Rectal cancer is a significant healthcare burden, and effective treatment is crucial. This research aims to compare the effectiveness of surgical and endoscopic resection, transanal resection, and radiotherapy. A literature analysis was conducted in order to identify relevant studies, by comparing the different surgical approaches and variables affecting treatment decisions. The findings were analyzed and synthesized to provide a comprehensive overview. Surgical treatment, particularly TME (total mesorectal excision), proved consistent efficacy in achieving complete tumor resection and improving long-term survival. Endoscopic treatment and transanal resection techniques were promising for early-stage tumors but were associated with higher local recurrence rates. Radiotherapy, especially in combination with chemotherapy, played a crucial role in locally advanced cases, improving local control and reducing recurrence risk. Patient data, tumor characteristics, and healthcare system factors were identified as important factors in treatment modality selection. Surgical treatment, specifically TME, remains the recommended standard approach for rectal cancer, providing excellent oncological outcomes. Endoscopic treatment and transanal resection techniques can be considered for selected early-stage cases, while radiotherapy is beneficial for locally advanced tumors. Treatment decisions should be personalized based on patient and tumor characteristics, considering the available resources and expertise within the healthcare system.


Female-specific wing degeneration is triggered by ecdysteroid in cultures of wing discs from the bagworm moth, Eumeta variegata (Insecta: Lepidoptera, Psychidae).
Female adults of the bagworm moth, Eumeta variegata, are completely wingless; by contrast, the male adults have functional wings. Sex-specific differences in the development of wing discs appear to arise during the 8th (penultimate) larval instar. We have previously found that the wing discs of female E. variegata terminate development and disappear during the prepupal period, whereas the wing discs of males continue to develop fully into adult wings. We have investigated the effects of ecdysteroid (20-hydroxyecdysone, 20E) when cultured with larval wing discs, which are normally attached to the larval integument of both male and female larvae. Male wing discs cultured with 20E undergo a remarkable transformation: the discs undergo apolysis and then differentiation. Female wing discs cultured with 20E also undergo apolysis; however, the disc cells enter apoptosis. We have observed condensed chromatin, fragmented nuclei, and secondary lysosomes in the epithelial cells of these female discs. This report establishes that the reduction of female wing discs arises through apoptotic events triggered by ecdysteroid in vitro.


In situ remediation-released zero-valent iron nanoparticles impair soil ecosystems health: A C. elegans biomarker-based risk assessment.
There is considerable concern over the potential ecotoxicity to soil ecosystems posed by zero-valent iron nanoparticles (Fe(0) NPs) released from in situ environmental remediation. However, a lack of quantitative risk assessment has hampered the development of appropriate testing methods used in environmental applications. Here we present a novel, empirical approach to assess Fe(0) NPs-associated soil ecosystems health risk using the nematode Caenorhabditis elegans as a model organism. A Hill-based dose-response model describing the concentration-fertility inhibition relationships was constructed. A Weibull model was used to estimate thresholds as a guideline to protect C. elegans from infertility when exposed to waterborne or foodborne Fe(0) NPs. Finally, the risk metrics, exceedance risk (ER) and risk quotient (RQ) of Fe(0) NPs in various depths and distances from remediation sites can then be predicted. We showed that under 50% risk probability (ER=0.5), upper soil layer had the highest infertility risk (95% confidence interval: 13.18-57.40%). The margins of safety and acceptable criteria for soil ecosystems health for using Fe(0) NPs in field scale applications were also recommended. Results showed that RQs are larger than 1 in all soil layers when setting a stricter threshold of ∼1.02mgL(-1) of Fe(0) NPs. This C. elegans biomarker-based risk model affords new insights into the links between widespread use of Fe(0) NPs and environmental risk assessment and offers potential environmental implications of metal-based NPs for in situ remediation.


Immunotoxicity of tannery effluent to the freshwater fish Cyprinous carpio.
This study was undertaken to determine the effect of chronic exposure to sub-lethal concentrations of tannery effluent (TE) on the humoral antibody response and the cell-mediated immune response of the fish Cyprinous carpio. The LC(50) value of the TE for C. carpio was determined by bioassay to be 3.8%. Sub-lethal concentrations of TE (0.6% and 0.3%) significantly suppressed the humoral and cell-mediated immune responses. Exposure of C. carpio to the TE had a significant effect on mean acceptance time (MAT) for transplanted scales. MAT was found to be 5-8 days for autografts and 4-7 days for allografts. The somatic indices of the kidney and spleen were reduced compared with controls.


Decision-making with and without information technology in acute care hospitals: survey in the United States.
These survey results are from a national survey of acute care hospitals. A random sample of 813 hospitals was selected with 115 responding and 33 incorrect addresses resulting in a 15% response rate. The purpose of the study was to measure the extent of information systems integration in the financial, medical, and administrative systems of the hospitals. Decision making with and without information technology is explored based upon the survey data. The results indicate why and how meetings are held. Necessary changes in the decision-making environment are identified for decision making utilizing information technology to be successful. These results will provide a benchmark for hospitals to determine their technology transfer position and to set goals for computer assisted decision-making.


Comparison of outcomes and costs of extracorporeal blood purification therapies in critically ill COVID-19 patients.
Plasmapheresis and hemoperfusion are used against cytokine release syndrome in COVID-19. This study aims to compare their outcomes, costs, and side-effects. Survival, costs and side-effects were compared in intensive care unit (ICU) patients receiving plasmapheresis (n = 49), hemoperfusion (n = 20), or none (n = 107), followed until death or discharge. Plasmapheresis survival time was higher than hemoperfusion or controls (HR = 0.764, p = 0.397 and HR = 0.483, p = 0.002, respectively), although the latter diminished after controlling for age and disease severity (p = 0.979). There was no significant difference in ICU costs for plasmapheresis and hemoperfusion (p = 0.738) while both costed more than controls (both p < 0.001). Hypocalcemia and thrombocytopenia incidence did not differ between two groups (p = 0.124 and p = 0.389, respectively) while being higher than controls in plasmapheresis (both p < 0.001) and hemoperfusion (p < 0.001 and p = 0.056, respectively). Plasmapheresis and hemoperfusion do not differ significantly in patient survival, ICU costs and side-effects with a higher incidence of hypocalcemia and thrombocytopenia compared witcontrols.


4D Printing of a Liquid Crystal Elastomer with a Controllable Orientation Gradient.
Liquid crystal elastomers (LCEs), a class of soft materials capable of a large and reversible change in the shape under the trigger of external stimuli, can be fabricated into diverse architectures with complicated deformation modes through four-dimensional (4D) printing. However, the printable LCE ink is only in the form of monomeric precursors and the deformation mode is limited to contraction/extension deformation. Herein, we report a novel approach to break through these limitations. We achieved 4D printing of a single-component liquid crystal polymer ink in its isotropy state through direct ink writing (DIW) technology. The drawing force imposed by the movement of nozzle in the extruded printing process was able to align the mesogen units along the specific printing path. An orientation gradient perpendicular to the printing direction was obtained due to the existence of a temperature gradient between the two sides of printed samples and could be further fixed by post-photo-cross-linking treatment through the dimerizable groups in the LCE, realizing a new actuation mode in the field of extrusion-based printing of LCE actuators. The printed film was able to change reversibly from a strip to a tightly hollow cylinder and could reversibly lift up an object with roughly 600 times its own weight. The orientation gradient can be patterned through liquid-assistant printing or programmed structure design to integrate both bending and contraction actuation modes on the same printed sample, leading to complex deformation and two-dimensional (2D) planar porous structure to three-dimensional (3D) porous cylinder transition. This study opens up a new prospect to directly print a wide variety of LCE actuators with versatile actuation modes.


Acute improvement in histological outcome by MK-801 following focal cerebral ischemia and reperfusion in the cat independent of blood flow changes.
The present study reports on the acute effects of MK-801 on the histopathological outcome and blood flow changes during focal cerebral ischemia and reperfusion. In addition, acute changes in the EEG and blood pressure are also reported. In 16 halothane-anesthetized cats, the left middle cerebral artery (MCA) was occluded for 2 h followed by 4 h of reperfusion. Thirty minutes after the onset of ischemia, eight animals were treated with 1 mg/kg of MK-801, while eight animals received saline. Blood flow from the peripheral MCA territory was measured with H2 clearance. There was a comparable reduction in blood flow (down to 20% of control) in the ischemic gyri of the two groups followed by a partial recovery after recirculation. There was a similar decrease in the EEG amplitude over the ischemic central MCA territory in the treated and the untreated group. Treatment with MK-801 induced a burst suppression in the EEG and a transient drop (11.4 +/- 6.5 mm Hg) in the mean arterial pressure. The volume of early ischemic damage decreased by one-third in the MK-801-treated group compared to the untreated one, both in the total hemisphere (from 29 +/- 10 to 20 +/- 5%) and in the hemispheric cortex (range 36 +/- 8 to 24 +/- 13%). A major fraction of this improvement was localized to the middle and posterior parietal (mainly perifocal) regions of the MCA territory. These results show that in our model, MK-801 improves histopathological outcome despite the lack of apparent effect on the cortical blood flow, and an adverse effect on the systemic blood pressure. This is the first report that describes data on a reproducible model of reperfusion after temporary occlusion of the MCA in a cat, extending the findings of the Glasgow group, who observed similar neuroprotection in models of permanent MCA occlusion.


The time-dependent hormetic effects of 1-alkyl-3-methylimidazolium chloride and their mixtures on Vibrio qinghaiensis sp. -Q67.
The hormetic effects of ionic liquids (ILs) were paid more ecological attentions. However, the time-dependent hormetic effects of ILs and their mixtures remained to be studied. In this paper, the time-dependent toxicities of five single ILs, 1-ethyl-, 1-butyl-, 1-hexyl-, 1-octyl-, and 1-dodecyl-3-methylimidazolium chlorides (named as [C2mim]Cl, [C4mim]Cl, [C6mim]Cl, [C8mim]Cl, and [C12mim]Cl, respectively), and their five-component mixtures to Vibrio qinghaiensis sp.-Q67 were determined at five exposure time points. For single ILs, [C2mim]Cl displayed significant hormetic effects at 2, 4, 8, and 12h; and [C4mim]Cl exhibited significant hormetic effects at 4, 8 and 12h; while [C6mim]Cl, [C8mim]Cl and [C12mim]Cl have not significant hormetic effects. At the same time point, the longer the side chain is, the larger the inhibition at high concentration is, and the less the stimulation at low concentration is. Meanwhile, the maximum stimulation effects were found between 4 and 8h. All six IL mixtures designed by uniform design ray showed significant hormetic effects at 8 and 12h. By means of the variable selection and modeling method based on the prediction (VSMP), it was found that the higher the concentration of [C2mim]Cl is, the stronger the mixture hormetic effect is and the higher the concentration of [C12mim]Cl is, the weaker the hormetic effect is.


Predictors of colorectal cancer knowledge and screening among church-attending African Americans and Whites in the Deep South.
This study examined colorectal cancer (CRC) knowledge and the relationship between knowledge, risk factors and screening behaviors among African Americans and Whites in the Deep South. One hundred and twenty three African Americans and Whites age-eligible for CRC screening were interviewed by telephone survey as part of a church-based CRC educational intervention. CRC knowledge was lower among those with less education, unemployed, Medicaid, Medicare, and less family income. Generally, participants who had more CRC knowledge were more likely to have engaged in screening behaviors. Participants who had a family history of CRC were more likely to have had a fecal occult blood test (OR = 2.55, 0.99-6.60) or barium enema (OR = 3.84, 1.44-10.24) than those without. Whites were more likely to have had a flexible sigmoidoscopy (OR = 4.17, 1.09-16.67), colonoscopy (OR = 7.14, 1.72-25) or barium enema (OR = 6.25, 1.67-25) than African Americans. Church-based CRC screening intervention programs should target African Americans, those with no family history of CRC, and those with less education.


The SleepStrip: an apnoea screener for the early detection of sleep apnoea syndrome.
Sleep apnoea svndrome (SAS) is a largely undiagnosed and prevalent disorder. It is associated with cardiovascular morbidity as well as excessive daytime sleepiness and poor quality of life. In the present study the SleepStrip, a novel screening device is introduced, which is low cost and easy to use and is aimed for widespread use. The results of three independent validation studies, which compared the SleepStrip score (Sscore) against "gold standard" polysomnographically-determined apnoea/ hypopnoea index (AHI), are reported both separately and combined. Four hundred and two patients suspected of SAS underwent full polysomnography recordings concomitantly with the use of the SleepStrip. For all samples combined, the correlation between AHI and Sscore was r=0.73, sensitivity and specificity values ranged from 80-86% and 57-86% respectively, and the area under the curve derived from receiver-operating characteristic curves ranged from 0.81-0.92 at varying AHI thresholds. Though not intended as a substitute for polysomnography, the SleepStrip may provide initial screening information, which may be useful in both clinical and experimental settings.


Minimally invasive surgery in pediatric cancer patients.
The specific use of minimally invasive surgery (MIS) in pediatric cancer patients is limited. We evaluated the 5-year experience at a single institution with MIS in children with malignancies. A retrospective review was undertaken of all MIS performed between November 1995 and October 2000. A total of 101 pediatric oncology patients underwent 113 MIS procedures-64 laparoscopic (57%) and 49 thoracoscopic (43%)-during this period. Laparoscopy was performed for diagnostic purposes in 27 cases (42%) and was successful in 25 (93%) cases. Laparoscopic tumor resection was performed in seven cases (11%). Thirty additional laparoscopic procedures (47%) were attempted for complications of the malignancy or its treatment. Four of these cases were converted to open laparotomies. Indications for thoracoscopy included the evaluation of a mediastinal mass (n = 7) or biopsy or resection of pulmonary lesions (metastatic, n = 31; infectious, n = 9). Fourteen cases (29%) had to be converted to open thoracotomy procedures, generally because of the inability to localize a lesion. The other 35 procedures were successful. The overall complication rate was 5%. No trocar site recurrences or infections were observed. We conclude that MIS in pediatric cancer patients is a safe and effective diagnostic modality. The role of MIS for primary tumor resection remains to be defined.


Curative laparoscopic surgery for early gastric cancer: five years experience.
Sixty-one patients who were diagnosed with mucosal gastric cancer have been successfully treated with two laparoscopic techniques at our institute from March 1992 to March 1997. One is laparoscopic wedge resection of the stomach using a lesion-lifting method for lesions of the anterior wall, the lesser curvature, and the greater curvature of the stomach. The other is laparoscopic intragastric mucosal resection for lesions of the posterior wall of the stomach and near the cardia or the pylorus. Indications are as follows: (1) preoperatively diagnosed mucosal cancer; (2) <25 mm diameter elevated lesions; and (3) <15 mm diameter depressed lesions without ulcer formation. Patients were discharged in 4 to 8 days uneventfully. There was no major complication or mortality. The resected specimens had sufficient surgical margins horizontally (16 +/- 5 and 8 +/- 4 mm, respectively) and vertically. In one patient histologic examination revealed slight tumor infiltration into the submucosal layer with lymphatic invasion. He underwent gastrectomy with lymph node dissection 1 month after surgery. Otherwise, histologic examination revealed curative surgery. All patients in the series have survived during the 4- to 65-month follow-up period. There have been two recurrences in the series, both of which were found near the staple line 2 years after the initial surgery and were still mucosal lesions. They were successfully treated by open gastrectomy and laser irradiation. A separate early gastric cancer was found 2 years after the initial surgery in one patient, who then underwent curative open gastrectomy. In conclusion, if the patients are selected properly, these laparoscopic procedures are curative, minimally invasive treatment for early gastric cancer.


Antibiotic therapy augments the efficacy of gemcitabine-containing regimens for advanced cancer: a retrospective study.
The addition of antibiotics reportedly augments the efficacy of gemcitabine (GEM) in tumor-bearing mice. However, whether this phenomenon is also observed in cancer patients remains unclear. In the present study, we aimed to assess whether antibiotics for treatment or prevention of infection augments treatment efficacies of GEM-containing regimens in patients with any type of cancer. Medical records of patients diagnosed with cancer histopathologically and treated with GEM-containing regimens (n=169) were retrospectively reviewed. Patients were assigned into two groups: antibiotics-untreated group (patients who were treated with GEM-containing regimens but without antibiotics) and antibiotics-treated group (patients who were treated with GEM-containing regimens plus antibiotics). Response rates, progression-free survival (PFS) time, and overall survival (OS) time were analyzed for each group. The response rates of the antibiotics-untreated and antibiotics-treated groups with GEM-containing regimens were 15.1% and 27.6%, respectively. The median PFS times of the antibiotics-untreated and antibiotics-treated groups were 2.5 (95% CI: 1.86-3.73) and 4.9 (95% CI: 3.47-6.0) months, respectively. The median OS times of the antibiotics-untreated and antibiotics-treated groups were 7.53 (95% CI: 5.63-9.57) months and 13.83 (95% CI: 10.83-16.43) months, respectively. The addition of antibiotics augments the treatment efficacies of GEM-containing regimens, and it may be a potential therapeutic option to improve treatment efficacies of GEM-containing regimens in patients with advanced cancer.


The Effectiveness of Neurofeedback Training in Algorithmic Thinking Skills Enhancement.
Although research on learning difficulties are overall in an advanced stage, studies related to algorithmic thinking difficulties are limited, since interest in this field has been recently raised. In this paper, an interactive evaluation screener enhanced with neurofeedback elements, referring to algorithmic tasks solving evaluation, is proposed. The effect of HCI, color, narration and neurofeedback elements effect was evaluated in the case of algorithmic tasks assessment. Results suggest the enhanced performance in the case of neurofeedback trained group in terms of total correct and optimal algorithmic tasks solution. Furthermore, findings suggest that skills, concerning the way that an algorithm is conceived, designed, applied and evaluated are essentially improved.


[Radioimmunological estimation of digoxin in urine (author's transl)].
When separating free and antibody bound digoxin, dextrancoated charcoal suspensions in protein-free urine dilutions develop an improve sieve effect which improves with aging of the suspensions. On addition of albumin to the dilution medium (buffer), the adsorptive capacities become stabilized. In urine dilutions less than of 1:50, false positive digoxin concentrations were measured. Determinations of 0-5 ng digoxin/ml in the diluted urine (1:100) and in the buffer solution show identical results. The recovery of added digoxin (1 ng and 2 ng/ml) is 100%; the lower detection limit is 3.6 mug/l urine. Between-assay variation for means of duplicates shows in the main measuring range (1.5-2.8 ng digoxin/ml) a variation coefficient less than of 4.5%; for a commercial test this value is distinctly higher. Dihydrodigoxin is measured at 3% only. Application of this method for measuring cumulative glycoside elimination of 5 healthy persons (0.5 mg digoxin daily intravenously during 2 weeks) results in a minimal interindividual variation of 5.1%. In a test preparation with a bioavailability of 94.6% the variation is 5.2%.


[What preoperative information do the parents of children undergoing surgery want?].
Parents feel fear and anxiety before surgery is performed on their child, and those feelings could obstruct their preparation for the surgery. Preoperative information could relieve those feelings. To determine the preoperative information needs of parents of children undergoing elective surgery. A study was conducted on the parents of children who underwent elective surgery. Demographic data of parents were recorded. Preoperative information received or would like to have received was assessed in terms of contents, methods, opportunity, place and informant. Descriptive statistics were used. Thirteen hundred parents were surveyed. More than 80% of them want preoperative information about anaesthesia, surgery, preoperative fasting, drugs and anaesthetic complications, monitoring, intravenous line management, pain treatment, postoperative feeding, anxiety control, hospitalisation room, recovery room, and entertainment in recovery room. Most want to be informed verbally, one to two weeks in advance and not on the same day of surgery. The informant should be the surgeon and in his office. In addition, they want information through leaflets, videos and simulation workshops, or guided tours. Parents need complete preoperative information about anesthesia, surgery and postoperative care, received verbally and in advance.


Dual visible light photoredox and gold-catalyzed arylative ring expansion.
A combination of visible light photocatalysis and gold catalysis is applied to a ring expansion-oxidative arylation reaction. The reaction provides an entry into functionalized cyclic ketones from the coupling reaction of alkenyl and allenyl cycloalkanols with aryl diazonium salts. A mechanism involving generation of an electrophilic gold(III)-aryl intermediate is proposed on the basis of mechanistic studies, including time-resolved FT-IR spectroscopy.


Neuromuscular reinnervation efficacy using a YFP model.
The gold standard reconstruction for facial reanimation is the functional muscle transfer. The reinnervation of a muscle is never complete, and clinical results are variable with 20% not achieving a satisfactory outcome. We hypothesise that this may be due to a mismatch between the characteristics of the donor nerve and transferred muscle. 81 YFP-16 and 14 YFP-H mice were studied in three intervention groups over three time periods. Two parameters were investigated: the number and surface area of reinnervated neuromuscular junctions and regenerating axons. An assessment was made of motor unit proportions. All cases of nerve repair and nerve graft, the neuromuscular junctions (NMJ) were completely reinnervated by regenerating axons. The number and calibre of the regenerating axons were significantly different from controls for both intervention groups. The motor units were smaller in both intervention groups. Reinnervation occurs after nerve repair or graft; however, the arbour was reinnervated by large numbers of much smaller axons. These axons showed some evidence of remodelling in the repair group, but not in the graft group. Neither group achieved the parameters of the control group. There were persistent qualitative changes to the morphology of both axons and junctions. Imaging documented both synkinesis and alterations that resemble those seen in ageing. Overall, the efficacy of reinnervation is very high with all NMJ reoccupied by regenerating axons. The way small axons are remodelled is different in the nerve repairs compared with the nerve grafts.


Predictors of rear seat belt use among U.S. adults, 2012.
Seat belt use reduces the risk of injuries and fatalities among motor vehicle occupants in a crash, but belt use in rear seating positions is consistently lower than front seating positions. Knowledge is limited concerning factors associated with seat belt use among adult rear seat passengers. Data from the 2012 ConsumerStyles survey were used to calculate weighted percentages of self-reported rear seat belt use by demographic characteristics and type of rear seat belt use enforcement. Multivariable regression was used to calculate prevalence ratios for rear seat belt use, adjusting for person-, household- and geographic-level demographic variables as well as for type of seat belt law in place in the state. Rear seat belt use varied by age, race, geographic region, metropolitan status, and type of enforcement. Multivariable regression showed that respondents living in states with primary (Adjusted Prevalence Ratio (APR): 1.23) and secondary (APR: 1.11) rear seat belt use enforcement laws were significantly more likely to report always wearing a seat belt in the rear seat compared with those living in a state with no rear seat belt use enforcement law. Several factors were associated with self-reported seat belt use in rear seating positions. Evidence suggests that primary enforcement covering all seating positions is an effective intervention that can be employed to increase seat belt use and in turn prevent motor vehicle injuries to rear-seated occupants.


Postexercise decrease in arterial blood pressure, total peripheral resistance and in circulatory responses to brief hyperoxia in subjects with mild essential hypertension.
The objective of our study was: (1) to compare the influence of moderate exercise on circulatory after-response in mildly hypertensive (n = 8) and normotensive male subjects (n = 9); (2) to examine the circulatory response to 3-min hyperoxic inactivation of arterial chemoreceptors at rest and during postexercise period in both groups. Hypertensive men (HTS) with a systolic blood pressure (SBP) 148 +/- 5 mm Hg, diastolic blood pressure (DBP) 92.4 +/- 4 mm Hg; and normotensive men (NTS), with a SBP 126 +/- 3 mm Hg, DBP 75.6 +/- 1.3 mm Hg, were submitted to 20-min of moderate exercise on a cycloergometer (up to the level of 55% of each subject's resting heart rate reserve). Finger arterial BP was recorded continuously with Finapres, impedance reography was used for recording stroke volume, cardiac output and arm blood flow. In HTS a significant decrease in SBP by 14.5 +/- 3.4 mm Hg, DBP by 8.9 +/- 1.9 mm Hg, total peripheral resistance (TPR) by 0.45 +/- 0.05 TPR u. (33.7 +/- 2.7%), and in arm vascular resistance (AVR) by 11.0 +/- 2.7 PRU u. (35.6 +/- 7%), was observed over a 60-min postexercise period. NTS exhibited insignificant changes in SBP, DBP, AVR except a significant decrease in TPR limited only to 20-min postexercise period. Hyperoxia decreased SBP, DBP and TPR in HTS. This effect was significantly attenuated during the postexercise period. Long-lasting antihypertensive effect of a single dynamic exercise in HTS suggests that moderate exercise may be applied as an effective physiological procedure to reduce elevated arterial BP in mild hypertension. We suggest also that the attenuation of the sympathoexcitatory arterial chemoreceptor reflex may contribute to a postexercise decrease in arterial BP and in TPR in mildly hypertensive subjects.


Reduction of Coronary Motion Artifacts in Prospectively Electrocardiography-Gated Coronary Computed Tomography Angiography Using Monochromatic Imaging at Various Energy Levels in Combination With a Motion Correction Algorithm on Single-Source Fast Tube Voltage Switching Dual-Energy Computed Tomography: A Phantom Experiment.
The aim of this study was to assess the effect of monochromatic imaging at various energy levels in combination with a motion correction algorithm (MCA) in single-source dual-energy coronary computed tomography angiography (CCTA) with fast switching of tube voltage on the reduction of coronary motion artifacts (CMA) in a phantom setting. Using this dual-energy computed tomography technique with a phantom comprising models of coronary vessels filled with contrast medium and pulsating at constant heart rates of 60 to 100 beats per minute, we reconstructed monochromatic images of CCTA obtained at 50 to 90 keV with and without use of MCA. Cardiac motion was modeled by simulating the in vivo time-volume curve of the left ventricle. Two independent readers graded CMA in 9 coronary segments using a 5-point scale (1, poor; 3 to 5, interpretable; 5, excellent). At each heart rate, we compared the average score of CMA between images obtained at 50 to 90 keV with and without use of MCA using Wilcoxon signed rank test, and we compared the score among images obtained at 50 to 90 keV with use of MCA using Kruskal-Wallis and post hoc tests. We also compared the percentages of image interpretability and improvement in image interpretability among images obtained at 50 to 90 keV with use of MCA. With the use of MCA, the average score of CMA was significantly higher for images obtained at each energy level from 50 to 70 keV (P < 0.05) and was comparable at 80 and 90 keV, and it was comparable among those obtained at 50 to 70 keV. With its use, the percentages of image interpretability were similarly high at 50 to 70 keV at 60 to 80 beats per minute (78%-100%), and they were higher at 50 to 60 keV (72%-83%) than at 70 keV at 90 to 100 beats per minute (50%-56%). The percentages of improved image interpretability with MCA were similarly high at 50 to 70 keV at 60 to 80 beats per minute (56%-100%), and they were higher at 50 to 60 keV (62%-77%) than at 70 keV at 90 to 100 beats per minute (36%-43%). The percentages of image interpretability and improved image interpretability with MCA were insufficient at 80 and 90 keV. Coronary motion artifacts were significantly reduced in images of monochromatic CCTA obtained at 50 to 70 keV in combination with MCA compared with those obtained without MCA, and the percentages of image interpretability and improved image interpretability with use of MCA were relatively high at 50 to 70 keV, and particularly at 50 to 60 keV, even at 90 to 100 beats per minute.


One-pot synthesis of xanthones and thioxanthones by the tandem coupling-cyclization of arynes and salicylates.
[reaction: see text] The reaction of silylaryl triflates, CsF, and salicylates affords a general and efficient way to prepare biologically interesting xanthones and thioxanthones. This chemistry presumably proceeds by a tandem intermolecular nucleophilic coupling and subsequent intramolecular electrophilic cyclization.


The effect of nalbuphine on gastrointestinal transit in mice.
Nalbuphine given subcutaneously (s.c.) inhibited gastrointestinal transit in a dose-dependent manner. Prior s.c. administration of naloxone hydrochloride suppressed the inhibitory effect of nalbuphine on gastrointestinal transit. Naloxone methobromide (naloxone MB), a quaternary compound, was also effective in antagonising this effect of nalbuphine but was less effective than naloxone hydrochloride. Furthermore, prior s.c. administration of Mr 2266 also antagonised the gastrointestinal transit inhibitory action of nalbuphine. When given centrally, either intracerebroventricularly (i.c.v.) or intracisternally (i.c.), naloxone hydrochloride was ineffective in antagonising s.c. nalbuphine. Similar findings were observed with centrally administered Mr 2266. In addition, i.c. nalbuphine had a minimal effect on gastrointestinal transit while i.c.v. nalbuphine only caused slight inhibition of gastrointestinal transit. It was concluded that nalbuphine inhibits gastrointestinal transit mainly through peripheral opiate receptors.


Measurement of cartilage sub-component distributions through the surface by Raman spectroscopy-based multivariate analysis.
Articular cartilage posesses unique material properties due to a complex depth-dependent composition of sub-components. Raman spectroscopy has proven valuable in quantifying this composition through cartilage cross-sections. However, cross-sectioning requires tissue destruction and is not practical in situ. In this work, Raman spectroscopy-based multivariate curve resolution (MCR) was employed in porcine cartilage samples (n = 12) to measure collagen, glycosaminoglycan, and water distributions through the surface for the first time; these were compared against cross-section standards. Through the surface Raman measurements proved reliable in predicting composition distribution up to a depth of approximately 0.5 mm. A fructose-based optical clearing agent (OCA) was also used in an attempt to further improve depth of resolution of this measurement method. However, it did not; mainly due to a high-spectral overlap with the Raman spectra of main cartilage sub-components. This measurement technique potentially could be used in situ, to better understand the etiology of joint diseases such as osteoarthritis (OA).


Chronic Ventricular Septal Defect and Retained Bullet After Gunshot: Best Not to Reopen Old Wounds.
Penetrating cardiac trauma from gunshots is usually fatal. We describe the case of a 62-year-old male presenting with ST-segment elevation myocardial infarction. A retained bullet embedded into the left ventricle was identified incidentally along with a ventricular septal defect from a gunshot wound decades prior. The ventricular septal defect and retained bullet were managed conservatively. (Level of Difficulty: Intermediate.).


In vivo confocal microscopy efficacy assessment of daylight photodynamic therapy in actinic keratosis patients.
Reflectance confocal microscopy (RCM) is a noninvasive diagnostic technique with an acceptable sensitivity and specificity for actinic keratosis (AK). We evaluated efficacy of daylight photodynamic therapy (DL-PDT) in patients with AK using a new RCM atypia scoring system. All patients with AK lesions (Grade I-II) were included in our study (2012-15). Baseline clinical, dermoscopy and RCM evaluations were followed by DL-PDT. In the first follow-up, clinical examination, dermoscopy and RCM imaging of the treated area were carried out. Atypia scoring and cell size measurements were used to compare before and after RCM images. From 40 lesions (20 patients with mean age of 75·5 years), complete resolution and partial response of the actinic damage was detected in 80% and 17·5% of lesions, respectively. No cellular atypia was seen in the follow-up RCM images of 57·5% of lesions (n = 23), while in 40% of lesions (n = 16) minimal changes to the honeycomb pattern of the epidermis were seen in the follow-up RCM images (atypia score 1). Only one lesion showed minimal or no clinical response, and a persistent moderate amount of atypia in RCM. Furthermore, atypia score and mean cell size decreased significantly in the follow-up DL-PDT RCM images (P < 0·001, P = 0·001, respectively). RCM features of actinic damage at cellular level have been shown to correlate well with the results of a clinical assessment of AK lesions. This study confirms that in vivo RCM technology might be an additional technique to monitor the efficacy of DL-PDT for AK.


Co-administration of Luteolin mitigated toxicity in rats' lungs associated with doxorubicin treatment.
Doxorubicin (DOX), is a drug against lung malignancies with undesirable side effect including oxidative, inflammatory and apoptotic effects. Luteolin (LUT), present in fruits and vegetables is pharmacologically active against oxido-inflammatory and apoptotic responses. The present study examined the effect of LUT on DOX-induced lungs and blood dysfunction in Wistars rat (sex: male; 10 weeks old, 160 ± 5 g). Randomly grouped (n = 10) rats were treated as follows: control, LUT alone (100 mg/kg; per os), DOX (2 mg/kg; i. p), and co-treated rats with LUT (50 or 100 mg/kg) and DOX for two consecutive weeks. DOX alone adversely altered the final body and relative organ weights, red and white blood cell and platelet counts. DOX significantly (p > 0.05) reduced lungs antioxidant capacity, and anti-inflammatory cytokines; increased biomarkers of oxidative stress, caspase-3 activity, and pro-inflammatory cytokine. Morphological damages accompanied these biochemical alterations in the lung of experimental rats. Co-treatment with LUT, dose-dependently reversed DOX-mediated changes in rats' survival, toxic responses, and diminished oxidative stress in rat's lungs. Furthermore, co-treatment with LUT resulted in the reduction of pro-inflammatory cytokines and apoptotic biomarkers, increased red and white blood cell, platelet counts and abated pathological injuries in rat lungs treated with DOX alone. In essence, our findings indicate that LUT dose-dependently mitigated DOX-induced toxicities in the lungs and haematopoietic systems. Supplementation of patients on DOX-chemotherapy with phytochemicals exhibiting antioxidant activities, specifically LUT, could circumvent the onset of unintended toxic responses in the lungs and haematopoietic system exposed to DOX.


Educational differentials on the transition to first birth in South Korea.
Drawing on two competing frameworks, the leader-follower model and the permanent-difference model, this study examines the educational gradient in the transition to first birth across birth cohorts in South Korea. The leader-follower model suggests that low fertility behaviour would spread from more educated women to their less educated counterparts, whereas the permanent-difference model posits that the gaps in fertility between education groups would remain distinct over time. Using nationally representative panel data of 7914 women (130,078 person-years) born between 1960 and 1984, results from discrete-time survival analysis show an initial convergence of gaps in fertility between education groups, but the gaps are now re-emerging and widening. Substantial gaps in fertility are found in younger birth cohorts born between 1975 and 1984. The convergence-divergence pattern observed over time highlights the importance of recognising how women's changing educational profile affects fertility in an ultra-low fertility setting.


Functions of the VEGF receptor-1 (FLT-1) in the vasculature.
Vascular endothelial growth factor (VEGF) is a major inducer of angiogenesis and vasculogenesis. Two distinct receptors for VEGF, the tyrosine kinase receptors VEGFR-1 (Flt-1) and VEGFR-2 (Flk-1/KDR), have been identified. Transfection studies could demonstrate biological activities for the Flk-1/KDR-, but not for the Flt-1-receptor, which led to the hypothesis that Flt-1 is a decoy receptor for VEGF. However, Flt-1 is biologically active in non-endothelial cells, namely monocytes, which exclusively express this receptor. In addition, the Flt-1 ligand placenta growth factor (PlGF), which is unable to bind and activate Flk-1/KDR, elicits activities in both monocytes and endothelial cells. The implications of Flt-1 mediated monocyte transmigration through endothelial monolayers and induction of the procoagulant tissue factor on monocytes for the field of vascular medicine are discussed.


The role of glucose-6-phosphate dehydrogenase in the evolution of longevity in Drosophila melanogaster.
Different polymorphic elements of the enzyme glucose-6-phosphate dehydrogenase (G6PD) are favoured under selection for long versus short life span. Replicate independently selected populations of short-lived individuals exhibit a more rapidly migrating and less actively staining allozyme, while long-lived populations have a slower migrating and more active allozyme. These correspond to the common ZwA and ZwB variants of the G6PD locus Zw. In vitro measurements show G6PD activity varies with allozymes and life span. Long-lived males have 64 per cent greater activity in G6PD, while females of long-lived strains are 108 per cent higher than those of short-lived strains. Previous studies of these strains have repeatedly demonstrated additivity of life span in F1 crosses. Activity of G6PD in reciprocal F1 populations is additive and intermediate between parents.


Gene delivery available in molluscan cells by strong promoter discovered from bivalve-infectious virus.
Understanding gene functions in marine invertebrates has been limited, largely due to the lack of suitable assay systems. Such a system requires investigative methods that are reproducible and can be quantitatively evaluated, such as a cell line, and a strong promoter that can drive high expression of a transgene. In this study, we established primary cell culture from a marine bivalve mollusc, Mizuhopecten yessoensis. Using scallop primary cells, we optimized electroporation conditions for transfection and carried out a luciferase-based promoter activity assay to identify strong promoter sequences that can drive expression of a gene of interest. We evaluated potential promoter sequences from genes of endogenous and exogenous origin and discovered a strong viral promoter derived from a bivalve-infectious virus, ostreid herpesvirus-1 (OsHV-1). This promoter, we termed OsHV-1 promoter, showed 24.7-fold and 16.1-fold higher activity than the cytomegalovirus immediate early (CMV IE) promoter and the endogenous EF1α promoter, the two most commonly used promoters in bivalves so far. Our GFP assays showed that the OsHV-1 promoter is active not only in scallop cells but also in HEK293 cells and zebrafish embryos. The OsHV-1 promoter practically enables functional analysis of marine molluscan genes, which can contribute to unveiling gene-regulatory networks underlying astonishing regeneration, adaptation, reproduction, and aging in marine invertebrates.


Community transmission of rotavirus infection in a vaccinated population in Blantyre, Malawi: a prospective household cohort study.
Rotavirus vaccine effectiveness is reduced among children in low-income countries. Indirect (transmission-mediated) effects of rotavirus vaccine might contribute to the total population effect of vaccination. We aimed to examine risk factors for transmission of rotavirus to household contacts in Blantyre, Malawi, and estimated the effectiveness of rotavirus vaccine in preventing transmission of infection to household contacts. In this prospective household cohort study, we recruited children born after Sept 17, 2012, and aged at least 6 weeks (vaccine-eligible children) with acute rotavirus gastroenteritis and their household contacts, in four government health facilities in Blantyre, Malawi. Clinical data, a bulk stool sample, and 1-2 mL of serum were collected from case children at presentation. Clinical data and stool samples were also prospectively collected from household contacts over 14 days from presentation. A single stool sample was collected from control households containing asymptomatic children who were frequency age-matched to case children. Samples were tested for rotavirus using semi-quantitative real-time PCR and for anti-rotavirus IgA using a semi-quantitative sandwich ELISA. Risk factors for household transmission of rotavirus infection and clinical disease, including disease severity and faecal shedding density, were identified using mixed effects logistic regression. Vaccine effectiveness against transmission was estimated as 1 minus the ratio of secondary attack rates in vaccinated and counterfactual unvaccinated populations, using vaccine effectiveness estimates from the associated diarrhoeal surveillance platform to estimate the counterfactual secondary attack rate without vaccination. Between Feb 16, 2015, and Nov 11, 2016, we recruited 196 case households (705 members) and 55 control households (153 members). Household secondary attack rate for rotavirus infection was high (434 [65%] of 665 individuals) and secondary attack rate for clinical disease was much lower (37 [5%] of 698). Asymptomatic infection in control households was common (40 [28%] of 144). Increasing disease severity in an index child (as measured by Vesikari score) was associated with increased risk of transmission of infection (odds ratio 1·17 [95% CI 1·06-1·30) and disease (1·28 [1·08-1·52]) to household contacts. Estimated vaccine effectiveness against transmission was 39% (95% CI 16-57). Rotavirus vaccine has the potential to substantially reduce household rotavirus transmission. This finding should be considered in clinical and health economic assessments of vaccine effectiveness. Wellcome Trust, US National Institutes of Health, and US National Institute of Allergy and Infectious Diseases.


Impacts of oxidants and antioxidants on the emergence and progression of Alzheimer's disease.
The brain shows a high sensitivity to oxidative stress (OS). Thus, the maintenance and homeostasis of the brain, in particular neural cells, regarding the reduction-oxidation (redox) situation is crucial for the regular function of the central nervous systems (CNS). The imbalance between the reactive oxygen species (ROS) and the cellular mechanism(s) might lead to the emergence of OS, resulting in possible cell death and tissue damages, and initiating neurodegenerative disorders (NDDs). Characterized by the cytoplasmic growth of neurofibrillary tangles and extracellular β-amyloid plaques, Alzheimer's disease (AD) is a complex NDD that causes dementia in adult life with severe manifestations. Nuclear factor erythroid 2-related factor 2 (NRF2) is a key transcription factor that regulates the functional expression of OS-related genes and the functionality of endogenous antioxidants in response to ROS. In the case of oxidative damage, NRF2 is transferred to the nucleus and attached to the antioxidant response element (ARE), which can subsequently enhance the functional expression of the cell-protecting genes. In this review, we impart on the key mechanisms engaged in the generation of active and reactive species of endogenous and exogenous oxidants and discuss the antioxidants as the defense system of neural cells regarding the NRF2-ARE signaling path in the CNS.


Improving stability and nitrogen removal performance of pilot-scale autotrophic process for mature landfill leachate treatment utilizing in-situ organics.
This study established a stable and efficient pilot-scale denitrification (DN) and partial nitritation (PN) combined with autotrophic nitrogen removal process for mature landfill leachate treatment. A total inorganic nitrogen removal efficiency (TINRE) of 95.3% was achieved without any external carbon source input, including 17.1%, 1.0% and 77.2% of nitrogen removal contributed by the DN, PN and autotrophic processes, respectively. ANAMMOX genus, Ca_Anammoxoglobus (19.4%) was dominant in autotrophic reactor. Moreover, denitrifying bacteria could utilize in-situ organics, including poorly degradable organics, to enhance the nitrogen removal performance of autotrophic process, contributing 3.4% of TINRE. This study provides new insights for the economical, low-carbon, and efficient treatment of mature landfill leachate.


Natural occurrence of mycotoxins in staple cereals from Ethiopia.
The occurrence of mycotoxins in barley, sorghum, teff (Eragrostis tef) and wheat from Ethiopia has been studied. Samples were analyzed for aflatoxin B(1) (AFB1), ochratoxin A (OTA), deoxynivalenol (DON), nivalenol (NIV) and zearalenone (ZEN) using high performance liquid chromatography (HPLC) and for fumonisins (FUM) using enzyme linked immunosorbent assay (ELISA). AFB1 and OTA were detected in samples of all the four crops. AFB1 was detected in 8.8% of the 352 samples analyzed at concentrations ranging from trace to 26 microg kg(-1). OTA occurred in 24.3% of 321 samples at a mean concentration of 54.1 microg kg(-1) and a maximum of 2106 microg kg(-1). DON occurred in barley, sorghum and wheat at 40-2340 microg kg(-1) with an overall incidence of 48.8% among the 84 mainly 'suspect' samples analyzed; NIV was co-analyzed with DON and was detected at 40 microg kg(-1) in a wheat sample and at 50, 380, and 490 microg kg(-1) in three sorghum samples. FUM and ZEN occurred only in sorghum samples with low frequencies at concentrations reaching 2117 and 32 microg kg(-1), respectively. The analytical results indicate higher mycotoxin contamination in sorghum, which could be related to the widespread storage of sorghum grain in underground pits leading to elevated seed moisture contents. This is the first report on the occurrence of OTA in teff.


Trial of Atorvastatin on Serum Interleukin-6, Total Antioxidant Capacity, C-Reactive Protein, and Alpha-1 Antitrypsin in Patients with Chronic Obstructive Pulmonary Disease.
The present study was designed to investigate the effects of atorvastatin on serum high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), total antioxidant capacity (TAC), and alpha-1 antitrypsin (AAT) in patients with chronic obstructive pulmonary disease (COPD). A clinical trial study conducted on 42 cases of COPD (Vali-Asr Hospital, Birjand, East of Iran, years 2014-16). Patients were randomly assigned to 21 controls and 21 cases who treated with atorvastatin (40 mg/day for 6 months). Inhaled corticosteroid and long-acting β-agonist were administrated in both groups. The trial was registered at the Iranian Registry of Clinical Trials (registration number: IRCT2016042527594N1). TAC was measured by ferric reducing/antioxidant power assay. An enzyme-linked immunosorbent assay was used to determine IL-6, AAT, and hs-CRP. Spearman's rho test and Wilcoxon, Mann-Whitney, paired, and independent t-tests were used for data analysis in SPSS 23. P < 0.05 was considered significant. A number of patients completed the study were 16 in atorvastatin and 18 in control group. Mean increments (μmol/L) of TAC (mean ± standard deviation [SD]) were 12.81 ± 605.25 (P = 0.68) in atorvastatin and 160.26 ± 280.54 (P = 0.14) in control group. Mean decrements of IL-6, CRP, and AAT (mean ± SD) were 1.41 ± 5.51 (P = 0.71), 0.98 ± 5.68 (P = 0.72), and 10.94 ± 46.83 (P = 0.21) in atorvastatin and 0.91 ± 11.70 (P = 0.75), 3.23 ± 7.00 (P = 0.19), and 18.77 ± 55.90 (P = 0.21) in control group. Atorvastatin did not succeed in maintaining TAC and CRP reduction. However, less reduction in AAT and more reduction in IL-6 in the atorvastatin group would be likely a beneficial effect in COPD.


Safety and efficacy of nivolumab, an anti-PD1 immunotherapy, in patients with advanced basal cell carcinoma, after failure or intolerance to sonic Hedgehog inhibitors: UNICANCER AcSé NIVOLUMAB trial.
Basal cell carcinoma (BCC) is the most common human malignancy. In most cases, BCC has slow progression and can be definitively cured by surgery or radiotherapy. However, in rare cases, it can become locally advanced or, even more rarely, metastatic. The alternative recommended treatments are Sonic Hedgehog pathway inhibitors; however, the response is often short-lived. This was a phase 2 basket study (NCT03012581) evaluating the efficacy and safety of nivolumab in a cohort of 32 advanced BCC patients, enrolled after failure of Sonic Hedgehog inhibitors, including 29 laBCC (91%) and 3 mBCC (9%). Compared to previously published studies, our population consisted of severe patients with a poor prognosis because they had already received multiple lines of treatment: all patients received previous Sonic Hedgehog inhibitors, 53% of patients already had chemotherapy and 75% radiotherapy. At 12 weeks, we reported 3.1% of complete responses, 18.8% of partial responses, and 43.8% of stable diseases. The best response rate to nivolumab reached 12.5% of complete responses (four patients), 18.8% of partial responses (three patients), and 43.8% of stable diseases (14 patients). Adverse events (AE) were mostly grade 2 or 3, slightly different to the adverse events observed in the treatment of metastatic melanoma (higher rate of diabetes, no thyroid dysfunction). Nivolumab is a relevant therapeutic option for patients with advanced relapsing/refractory BCC.


Improving mental health in Multiple Sclerosis with an interpersonal emotion regulation intervention: A prospective, randomized controlled trial.
Over a third of people with Multiple Sclerosis (PwMS) struggle with poor mental health, which exacerbates physical symptoms and complicates clinical treatment. To address this, we tested the efficacy of an interpersonal emotion regulation intervention: this intervention seeks to improve mental health by teaching participants to use emotion regulation strategies which leverage social support (e.g., reaching out to others for comfort when experiencing a stressful event). Nineteen PwMS completed this prospective, blinded randomized controlled trial (intervention n = 10; control n = 9). Intervention participants met with an interventionist over six weeks to discuss their emotional challenges and develop goals to use interpersonal emotion regulation strategies. Participants in the control condition met with the interventionist on the same schedule but their emotion regulation strategies were only measured and not manipulated. Pre-registered primary outcomes were self-reported depression, stress, and quality of life (QoL). The pre-registered secondary outcome was self-reported social support. Intervention participants' depression scores improved from time 1 to time 2 (mean difference=3.60, 95% CI [0.44-6.76]), yet remained unchanged for the control group (mean difference=-1.67, 95% CI [-5.00-1.67], overall interaction, F(1,17)=5.84, p=.027, ηp2=.256). The remaining primary (stress and QoL) and secondary (social support) outcomes did not show a significant effect of the intervention (stress: p=.601, ηp2=.016; QoL: p=.179, ηp2=.104; social support: p=.140, ηp2=.124). Interpersonal emotion regulation is beneficial in improving depression in PwMS. Consequently, these strategies can be implemented in conjunction with existing mental health treatments in a holistic approach to improving well-being.


Improved permeability and antifouling performance of polyethersulfone ultrafiltration membranes tailored by hydroxyapatite/boron nitride nanocomposites.
To extend the use of polyethersulfone (PES) ultrafiltration membranes in water process engineering, the membrane's wettability and anti-fouling properties should be further improved. In this context, hydroxyapatite/boron nitride (HAp/BN) nanocomposites have been prepared and intercalated into PES membranes using a non-solvent-induced phase separation process. High-quality 2D transparent boron nitride nanosheets (BN NSs) were prepared using an environmentally friendly and green-template assisted synthesis method in which 1D hexagonal hydroxyapatite nanosheets (HAp NRs) were uniformly distributed and hydrothermally immobilized at 180 °C. SEM, XRD, and Raman spectroscopy techniques were used to characterize the HAp/BN nanocomposites. PES membranes intercalated with various nanocomposite amounts (0-4 wt %) were also characterized by permeability, porosity, and contact angle measurements. Additional pathways for water molecule transport were promoted by the high surface area of the BN NSs, resulting in high permeability. Membrane wettability and antifouling properties were also improved by the inclusion of negative charge groups (OH- and PO43-) on HAp. Hybrid membranes containing 4 wt% HAp/BN showed the best overall performance with ∼97% increase in water flux, 90% rejection of bovine serum albumin (BSA), high water flux recovery ratio, low irreversible fouling, and high reversible fouling pattern. The intercalation of HAp/BN with the PES matrix therefore opens up a new direction to enhance the PES UF membranes' hydrophilicity, water flux, and antifouling capacity.


Atorvastatin enhances angiogenesis to reduce subdural hematoma in a rat model.
Statins are active in reducing plasma lipids, suppressing inflammation and promoting angiogenesis. Because angiogenesis is critical for the absorbance of subdural hematoma (SDH), we hypothesize that atorvastatin promotes angiogenesis to enhance hematoma absorption. SDH was induced in adult Wistar rats and treated with 3mg/kg, 8mg/kg of atorvastatin, or vehicle saline daily for 7days. The treated rats were examined for the level of CD34+/CD133+ endothelial progenitor cells (EPCs) in the circulation by flow cytometry, hematoma volumes by magnetic resonance imaging (MRI), and changes in cognitive functions. We also examined angiogenesis in the hematoma wall by transmission electronic microscopy and immunohistochemistry for the expression of vascular endothelial growth factor (VEGF), matrix metalloprotease 9 (MMP 9) and angiopoietin. SDH volume was significantly reduced and neurological deficits improved in rats receiving the low dose atorvastatin compared to those receiving either the high dose of atorvastatin or saline. Consistent with these outcome measures, the low dose atorvastatin increased the expression of angiopoient-1 and VEGF and reduced MMP9 expression in the connective tissue of the SDH wall, resulting in an increased vascular density and enhanced vascular maturation. The low-dose atorvastatin is effective in reducing SDH and improving neurological deficits in a rat model, primarily by promoting angiogenesis and vascular maturation.


BM-MSCs-derived microvesicles promote allogeneic kidney graft survival through enhancing micro-146a expression of dendritic cells.
Microvesicles (MVs) are plasmalemmal vesicles that are released from various cells and regarded as a mediator of intermolecular communication. In present study, we aimed to evaluate the therapeutic efficacy of the bone marrow mesenchymal stem cells (BM-MSCs)-derived MVs in the mice kidney transplant model and explored the underlying mechanism. BM-MSCs were isolated from C57BL/6 mice and identified using flow cytometry. In vivo allogenic kidney transplantation model of mice was performed between C57BL/6 mice (recipient) and BALB/c mice (donor). Recipient-type BM-MSC (0.1ml) or equal volume of medium as a control was injected i.v. 24h after kidney transplantation. Serum was collected for creatinine concentration detection at 14 d after transplantation. Dendritic cells (DCs) phenotype and miR-146a expression level in plant was identified. Immature DCs (iDCs) and mature DCs (mDCs) were derived from monocytes. MVs were separated from BM-MSCs. BM-MSCs positive for CD29 (95.8%) and CD44 (94.7%) were cultured and confirmed to prolong the allogenic kidney graft survival in mice. Importantly, the expression of miR-146a increased significantly in DCs of BM-MSCs-treated allogenic kidney. Moreover, both BM-MSCs and MVs derived from BM-MSCs enhanced miR-146a expression in iDCs and mDCs in vitro. Furthermore, MVs substantially reduced IL-12 mRNA expression and IL-12 production of mDCs whereas this action was reversed by miR-146a silencing. MiR-146a silencing also abrogated the MVs-induced decrease in serum creatinine, reduction of immature DCs phenotype in transplant and increase in miR-146a expression level. In summary, our data suggested that the BM-MSCs-derived MVs improved allogenic kidney transplantation survival through inhibiting DCs maturity by miR-146a.


Anti-inflammatory effect of Vaccinium oldhamii stems through inhibition of NF-κB and MAPK/ATF2 signaling activation in LPS-stimulated RAW264.7 cells.
Vaccinium oldhamii (V. oldhamii) has been reported to exert a variety of the pharmacological properties such as anti-oxidant activity, anti-cancer activity, and inhibitory activity of α-amylase and acetylcholinesterase. However, the anti-inflammatory activity of V. oldhamii has not been studied. In this study, we aimed to investigate anti-inflammatory activity of the stem extracts from V. oldhamii, and to elucidate the potential mechanisms in LPS-stimulated RAW264.7 cells. Cell viability was evaluated by MTT assay. The determination of NO and PGE2 production was performed using Griess reagent and Prostaglandin E2 ELISA Kit, respectively. The change of mRNA or protein level was evaluated by RT-PCR and Western blot. Among VOS, VOL and VOF, the inhibitory effect of NO and PGE2 production induced by LPS was highest in VOS treatment. Thus, VOS was selected for the further study. VOS dose-dependently blocked LPS-induced NO and PGE2 production by inhibiting iNOS and COX-2 expression, respectively. VOS inhibited the expression of pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α. In addition, VOS suppressed TRAP activity and attenuated the expression of the osteoclast-specific genes such as NFATc1, c-FOS, TRAP, MMP-9, cathepsin K, CA2, OSCAR and ATPv06d2. VOS inhibited LPS-induced NF-κB signaling activation through blocking IκB-α degradation and p65 nuclear accumulation. VOS inhibited MAPK signaling activation by attenuating the phosphorylation of ERK1/2, p38 and JNK. Furthermore, VOS inhibited ATF2 phosphorylation and blocked ATF2 nuclear accumulation. These results indicate that VOS may exert anti-inflammatory activity by inhibiting NF-κB and MAPK/ATF2 signaling. From these findings, VOS has potential to be a candidate for the development of chemopreventive or therapeutic agents for the inflammatory diseases.


Synergetic Tuning of the Electrical and Thermal Transport Properties via Pb/Ag Dual Doping in BiCuSeO.
The influence of Pb/Ag dual doping on the thermoelectric performance of BiCuSeO was investigated. It reveals that the electrical conductivity can be obviously improved owing to the increased carrier concentration mostly caused by the divalent Pb2+ doping at trivalent Bi3+. The electrical conductivity improves from 7.29 S/cm for BiCuSeO to 397.40 S/cm for Pb0.06Bi0.94Cu0.94Ag0.06SeO and Pb0.06Bi0.94CuSeO at 327 K. Combined with the moderate Seebeck coefficient (>120 μV/K) due to the large effective mass, a large power factor with 834 μW/mK2 is achieved. Meanwhile, the lattice thermal conductivity is visibly decreased, mainly benefiting from the substitution of Ag+ at the Cu+ site since the phonon scattering can be enhanced by mass fluctuation and strain fluctuation between the two elements. Thus, the total thermal conductivity is suppressed effectively compared with the Ag-free sample Pb0.06Bi0.94CuSeO. Finally, a maximum ZT value with nearly 1.0 has been obtained for Pb0.06Bi0.94Cu0.94Ag0.06SeO at 873 K, which is ∼64% and ∼47% larger than those of the pristine sample BiCuSeO and Ag-free sample Pb0.06Bi0.94CuSeO. Additionally, the ZT is also larger than the maximum value for the reported Pb-free samples BiCu0.94Ag0.06SeO and Bi0.92Ag0.08CuSeO, suggesting Pb and Ag are effective codopants of BiCuSeO to synergetically tune its electrical and thermal transport properties.


Prognostic value of De Ritis ratio in patients with acute myocardial infarction.
The association between aspartate aminotransferase to alanine aminotransferase ratio (De Ritis ratio) and prognosis of patients with acute myocardial infarction (AMI) remains poorly investigated. This study included 3000 patients with AMI undergoing percutaneous coronary intervention. Patients were categorized in groups according to tertiles of the De Ritis ratio: tertile 1 (De Ritis ratio < 1.11; 905 patients), tertile 2 (De Ritis ratio 1.11 to 1.95; 1003 patients) and tertile 3 (De Ritis ratio > 1.95; 1002 patients). The primary endpoint was 3-year all-cause mortality. At 3 years, all-cause deaths occurred in 487 patients: 119 deaths (13.2%) in patients of 1st tertile, 164 deaths (17.8%) in patients of 2nd tertile and 204 deaths (21.9%) in patients of 3rd tertile of the De Ritis ratio (adjusted hazard ratio [HR] = 1.16, 95% confidence interval [CI] 1.02 to 1.31], P = 0.023 per unit increment in the logarithmic scale of the De Ritis ratio); cardiac deaths occurred in 328 patients: 76 deaths (8.2%) in patients of 1st tertile, 110 deaths (12.0%) in patients of 2nd tertile and 142 deaths (15.4%) in patients of 3rd tertile of the De Ritis ratio (adjusted HR = 1.20 [1.04-1.40], P = 0.014 per unit increment in the logarithmic scale of De Ritis ratio). The C-statistic of the multivariable model(s) with baseline data without and with De Ritis ratio was 0.822 [0.805-0.839] and 0.823 [0.805-0.840], (P = 0.419) for all-cause mortality and 0.831[0.811-0.852] and 0.832 [0.811-0.853], P = 0.621) for cardiac mortality. In patients with AMI, elevated De Ritis ratio was associated with increased risk of 3-year mortality.


Potential Application of Orofacial MSCs in Tissue Engineering Nerve Guidance for Peripheral Nerve Injury Repair.
Injury to the peripheral nerve causes potential loss of sensory and motor functions, and peripheral nerve repair (PNR) remains a challenging endeavor. The current clinical methods of nerve repair, such as direct suture, autografts, and acellular nerve grafts (ANGs), exhibit their respective disadvantages like nerve tension, donor site morbidity, size mismatch, and immunogenicity. Even though commercially available nerve guidance conduits (NGCs) have demonstrated some clinical successes, the overall clinical outcome is still suboptimal, especially for nerve injuries with a large gap (≥ 3 cm) due to the lack of biologics. In the last two decades, the combination of advanced tissue engineering technologies, stem cell biology, and biomaterial science has significantly advanced the generation of a new generation of NGCs incorporated with biological factors or supportive cells, including mesenchymal stem cells (MSCs), which hold great promise to enhance peripheral nerve repair/regeneration (PNR). Orofacial MSCs are emerging as a unique source of MSCs for PNR due to their neural crest-origin and easy accessibility. In this narrative review, we have provided an update on the pathophysiology of peripheral nerve injury and the properties and biological functions of orofacial MSCs. Then we have highlighted the application of orofacial MSCs in tissue engineering nerve guidance for PNR in various preclinical models and the potential challenges and future directions in this field.


Gender and Racial Diversity Among Colon and Rectal Surgery Trainees and Leaders.
Despite recent changes in women and underrepresented minorities in medicine, there still exists large gender and racial gaps in surgical training and leadership. We hypothesize that gender and racial representation have improved among general and colorectal surgical trainees and leadership over the past 20 years. This cross-sectional study examines gender and racial representation of general and colorectal surgery residents, colorectal faculty members, and the American Society of Colon and Rectal Surgeons Executive Council. We extracted data from the Journal of the American Medical Association Graduate Medical Education yearly reports for information on surgical residents. We used the American Society of Colon and Rectal Surgeons website and publicly available practice websites to obtain information regarding colon and rectal surgery residents, faculty members, and the American Society of Colon and Rectal Surgeons Executive Council. We primarily focused on the gender and underrepresented minority breakdowns of general surgery residents, colorectal surgery residents, and the American Society of Colon and Rectal Surgeons Executive Council. We found that between 2001 and 2021, the number of women and people identifying as underrepresented minorities increased within general surgery programs. In addition, there has been a similar increase in underrepresented minorities and women entering colorectal surgery residency programs. Finally, there has been a steady, significant increase in women representation in the American Society of Colon and Rectal Surgeons Executive Council, with a slower increase in underrepresented minorities on the council. The study is limited by using previously collected data and relying on publicly available profiles for gender and race information. General and colon and rectal surgery have significantly increased gender and racial diversity at the training and leadership levels. ANTECEDENTES: A pesar de los cambios recientes en las mujeres y las minorías subrepresentadas en la medicina, todavía existen grandes brechas de género y raza en la capacitación y el liderazgo quirúrgico.OBJETIVO: Presumimos que la representación racial y de género ha mejorado entre los pasantes y el liderazgo en cirugía general y colorrectal en los últimos 20 años.DISEÑO: Este es un estudio transversal que examina la representación racial y de género de los residentes de cirugía general y colorrectal, miembros de la facultad colorrectal y el Consejo Ejecutivo de la Sociedad Estadounidense de Cirujanos de Colon y Recto.CONFIGURACIÓN: Extrajimos datos de los informes anuales de Educación Médica para Graduados del Journal of the American Medical Association para obtener información sobre los residentes quirúrgicos. Utilizamos el sitio web de la Sociedad Estadounidense de Cirujanos de Colon y Recto, así como los sitios web de práctica disponibles públicamente para obtener información sobre los residentes de cirugía de colon y recto, miembros de la facultad y el Consejo Ejecutivo de la Sociedad Estadounidense de Cirujanos de Colon y Recto.MEDIDAS PRINCIPALES DE RESULTADO: Nos enfocamos principalmente en los desgloses de género y minorías subrepresentadas de residentes de cirugía general, residentes de cirugía colorrectal y el Consejo Ejecutivo de la Sociedad Estadounidense de Cirujanos de Colon y Recto.RESULTADOS: Encontramos que entre 2001 y 2021, la cantidad de mujeres y personas que se identificaron como minorías subrepresentadas aumentó dentro de los programas de cirugía general. Además, ha habido un aumento similar en minorías subrepresentadas y mujeres que ingresan a programas de residencia en cirugía colorrectal. Finalmente, ha habido un aumento constante y significativo en la representación de mujeres en el Consejo Ejecutivo de la Sociedad Estadounidense de Cirujanos de Colon y Recto con un aumento más lento en las minorías subrepresentadas en el consejo.LIMITACIONES: El estudio está limitado por el uso de datos recopilados previamente y por confiar en perfiles disponibles públicamente para la información de género y raza.CONCLUSIONES: La cirugía general y de colon y recto han hecho algunos avances significativos en el aumento de la diversidad racial y de género en los niveles de formación y liderazgo. (Traducción-Yesenia.Rojas-Khalil ).