Tumor-host interactions: the role of inflammation.
It is well established that interactions between tumor cells and the host tissue stroma play a key role in determining whether and how any given solid malignancy will develop. In most cases, tumor cells hijack stromal cell functions for their own benefit and ultimately dictate the rules of engagement to the host tissue microenvironment. However, the contribution of the different stromal cell components to tumor growth remains to be clarified. Because most solid tumors are accompanied by a local inflammatory response, it has long been thought that inflammation and carcinogenesis are related. If formal proof that cancer can be initiated by inflammation in the absence of exogenous carcinogens is still lacking, there is abundant evidence that the inflammatory response can play a central role in modulating tumor growth and progression. This review will discuss some of the mechanisms whereby inflammation can both enhance and inhibit tumor growth.


Modeling and simulation of fructooligosaccharides synthesis in a batch basket reactor.
Fructooligosaccharides (FOS) production was carried out in a batch basket reactor with immobilized fructosyltransferase from Rhodotorula sp. from 500×10(3) g m(-3) of sucrose in 50 mM sodium acetate buffer at pH 6.0, 48 °C at 85 rpm and with an activity of 22.44×10(3) U m(-3). The experimental data were well adjusted to the mathematical model for FOS production using SIMULINK(®) (MATLAB(®)). The highest regression coefficient (R(2)>90%) and the lowest percentual residual standard deviation (%RSD<4.0) and chi-square (χ(2) <1.0) were obtained for sucrose (GF), kestose (GF2) and total FOS. The mass transfer coefficient (kL) was determined as 5.6×10(-5) m h(-1) and the diffusivity (DS) was 2.11×10(-11) m(2) s(-1). The best predicted FOS yield (after 96 h) was 60.62%, with an equivalent productivity of 3.16×10(3) g m(-3) h(-1). These results reaffirm the good potential of this enzyme for industrial application and, in addition, are in conformation to other studies conducted with the same enzyme from the same and different microbial sources.


Ureteral reimplantation for pediatric vesicoureteral reflux and primary obstructive megaureter: Transvesicoscopic cohen vs. Politano-Leadbetter approaches.
Transvesicoscopic approaches for ureteral reimplantation (UR) are effective surgical techniques with which to resolve vesicoureteral reflux (VUR) or primary obstructive megaureter (POM) in pediatric patients. However, the effectiveness of different UR surgical methods for these two diseases is still unclear. To compare the effects of Cohen's cross-trigonal and Politano-Leadbetter techniques in children in need of UR. A retrospective chart review was performed for consecutive patients who underwent UR at our institution between May 2018 and November 2019, including those treated for vesicoureteral reflux (VUR) or primary obstructive megaureter (POM). Patients who underwent Cohen's technique included in Group C, and those who underwent the Politano-Leadbetter technique were included in Group P. Patient characteristics, perioperative parameters, and short-term postoperative outcomes were compared. Forty-six patients who underwent unilateral UR were included in the analysis. At presentation, those in Group P (N = 22, 12 diagnosed with VUR and 10 with POM) did not differ from those in Group C (N = 24, 12 diagnosed with VUR and 12 with POM) with respect to age, sex, disease type or severity. For VUR patients, reflux was clinically resolved for all patients in both groups; however, only a 75% resolution rate was observed in Group C, with 3 patients experiencing persistent low-grade, clinically insignificant reflux, while a 100% resolution rate was found in Group P (P > 0.05). Among POM patients, the obstruction was resolved for all those in Group P and for 90% of those in Group C; this difference was also not statistically significant (P > 0.05). At the 1-year follow-up, the ureteral diameter (P < 0.05) and anterior-posterior renal pelvic diameter (APRPD) (P < 0.05) of Group P were significantly reduced, and differential renal function (DRF) (P < 0.05) was slightly improved compared with that in Group C in both VUR and POM patients. Politano-Leadbetter and Cohen are both reliable techniques for UR in children with VUR or POM, and the short-term outcomes of these methods in solving reflux and obstruction are comparable. Besides traditional Cohen's technique, Politano-Leadbetter's technique maybe a potential choice for ureteral reimplantation in children.


A review and critique of academic lab safety research.
Over the past ten years, there have been several high-profile accidents in academic laboratories around the world, resulting in significant injuries and fatalities. The aftermath of these incidents is often characterized by calls for reflection and re-examination of the academic discipline's approach to safety research and policy. However, the study of academic lab safety is still underdeveloped and necessary data about changes in safety attitudes and behaviours has not been gathered. This Review article critically examines the state of academic chemical safety research from a multifactorial stance, including research on the occurrence of lab accidents, contributors to lab accidents, the state of safety training research and the cultural barriers to conducting safety research and implementing safer lab practices. The Review concludes by delineating research questions that must be addressed to minimize future serious academic laboratory incidents as well as stressing the need for committed leadership from our research institutions.


Paeoniflorin, the main active constituent of Paeonia lactiflora roots, attenuates bleomycin-induced pulmonary fibrosis in mice by suppressing the synthesis of type I collagen.
In the theory of traditional Chinese medicine, pulmonary fibrosis (PF) belongs to pulmonary arthralgia, which means blood stasis in lung tissue. The roots of Paeonia lactiflora Pall are usually used to relieve the symptoms of this disease by promoting blood circulation and removing blood stasis. Paeoniflorin, the main active ingredient of P. lactiflora, may have anti-PF potential. This study aimed to investigate the effects and underlying mechanisms of paeoniflorin on bleomycin (BLM)-induced PF in mice. The PF model was established in mice by an intratracheal instillation of BLM. Paeoniflorin (25, 50, 100mg/kg) and prednisone (6mg/kg), as a positive control, were orally administered for consecutive 21 days. Histopathological changes were evaluated by hematoxylin and eosin stain and Masson's trichrome stain. The content of hydroxyproline was detected by using kits. The contents of type I collagen, TGF-β1 and IFN-γ were detected by ELISA. The levels of α-SMA, Smad4, Smad7 and the phosphorylations of Smad2/3 were detected by western blot. The mRNA expressions of MMP-1 and TIMP-1 were detected by RT-PCR. In mice treated with BLM, paeoniflorin (50mg/kg) significantly prolonged the survival periods, attenuated infiltration of inflammatory cells, interstitial fibrosis, and deposition of extracellular matrix in lung tissues. It also decreased the contents of hydroxyproline (a marker of collagens), type I collagen and α-SMA (an indicator of myofibroblasts) in lung tissues of mice. Paeoniflorin down-regulated the expressions of TGF-β1, Smad4 and the phosphorylations of Smad2/3, while up-regulated the expression of Smad7 in lung tissues. Moreover, paeoniflorin increased the content of IFN-γ. But, it only slightly affected mRNA expressions of MMP-1 and TIMP-1 in lung tissues of mice. Paeoniflorin attenuates PF by suppressing type I collagen synthesis via inhibiting the activation of TGF-β/Smad pathway and increasing the expression of IFN-γ.


A seven-nuclear receptor-based prognostic signature in breast cancer.
Breast cancer (BRCA) is a malignant cancer that threatened the life of female with unsatisfactory prognosis. The aim of this study was to identify prognostic nuclear receptors (NRs) signature of BRCA. BRCA patient samples were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Consensus clustering analysis, univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) Cox regression analysis were performed to evaluate, select NRs as prognostic factors and build Risk Score model. GSEA analysis was explored to check signaling differences between High- and Low-Risk group. Nomogram model basing on age and Risk Score was established to predict the 1-, 3- and 5-year survival. Model performance was assessed by a time-dependent receiver operating characteristic (ROC) curve and calibration plot. CIBERSORT, ESTIMATE and TIMER algorithm were introduced to evaluate the immune landscape. NR3C1, NR4A3, THRA, RXRG, NR2F6, NR1D2 and RORB were optimized as a prognostic signature for BRCA. This seven-NR-based Risk Score could effectively predict overall survival status. The area under the curve (AUC) of 1-, 3- and 5-year overall survival are 0.702, 0.734 and 0.722 in TCGA training cohort, and 0.630, 0.721 and 0.823 in GEO validation cohort, respectively. Calibration plot demonstrated satisfactory agreement between predictive and observed outcomes. Nomogram model worked well on predicting survival probabilities. Multiple cancer-related pathways were highly enriched in High-Risk group. High- and Low-Risk groups showed significant differed immune cell infiltration. There exists an obvious connection between Risk Score and immune checkpoints LAG3, PD1 and TIM3. The seven-NR-based Risk Score represents a promising signature for estimating overall survival in patients with BRCA, and is correlated with the immune microenvironment.


Development of Next-Generation Immunomodulatory Antibodies for Cancer Therapy through Optimization of the IgG Framework.
In this issue of Cancer Cell, Dahan and colleagues demonstrate that the Fc region has a significant impact on the therapeutic capacity of checkpoint inhibitor antibodies targeting the PD-1/PD-L1 axis in pre-clinical tumor models. This work provides important insights with respect to the further clinical development of checkpoint inhibitors.


Corrigendum: miR-548d-3p Is Up-regulated in Human Visceral Leishmaniasis and Suppresses Parasite Growth in Macrophages.
[This corrects the article DOI: 10.3389/fcimb.2022.826039.].


ROOT parameters of sugarcane and soil compaction indicators under deep strip tillage and conventional tillage.
Soil tillage and agricultural traffic generate changes in soil physical attributes and affect the growth of the roots. This study evaluates the impact of system soil tillage on compaction and sugarcane root growth. The experiment was carried out on a Rhodic Kandiudox with two soil tillages (Deep Strip Tillage and Conventional Tillage) and two positions (beds or traffic lane and no traffic lane), totaling four treatments (DST-beds + no traffic lane, DST-traffic lane, CT-no traffic lane and CT-traffic lane). Soil penetration resistance (SPR), bulk density, dry mass, and root system lengths and volumes were evaluated. DST-beds presented lower values for SPR (1.45 MPa) compared to the other treatments (2.55 MPa). This lower SPR did not reflect significant increases in root growth in relation to the DST-traffic lane, meaning that the roots were not confined to the beds. The dry root mass for CT- traffic lane was 35% less than for DST- traffic lane, and CT-no traffic lane reduced of the root dry mass in the layers 0.0-0.2 and 0.2-0.4 m by 62% and 47%, respectively, compared to the DST-beds. Therefore, CT, although widely used, does not create adequate conditions for root development in the first sugarcane cycle, even in lanes with no traffic.


Neurophysiological markers of contextual processing: the relationship between P3b and Gamma synchrony and their modulation by arousal, performance and individual differences.
The ability to identify and respond to significant events in the environment is a vital aspect of human cognition and yet is poorly understood as a dynamic neural process. While the response to a contextually-relevant stimulus involves a number of complimentary processes, including selective attention and neural binding, it is also subject to modulation by factors like arousal, age and sex. Adopting an integrative approach, we investigated contextual processing (as indexed by P3b and Gamma phase synchrony) in 120 healthy subjects performing an auditory oddball task while controlling for these other modulating factors. Results suggest a relationship between P3b and Gamma-2 synchrony in posterior regions only, with phasic anterior processing seemingly unrelated to that in posterior regions. However, only the P3b was significantly correlated to central and autonomic arousal. Further, while age and sex were associated with variation in individual measures, they did not strongly affect the relationship between the measures. We concluded that, in simple contextual processing, global and local elements of target stimuli are processed in parallel with little variation being shown between the sexes or resulting from increasing age.


Rhodiola crenulata extract suppresses hepatic gluconeogenesis via activation of the AMPK pathway.
Rhodiola, a popular herb, has been used for treating high altitude sicknesses, depression, fatigue, and diabetes. However, the detailed mechanisms by which Rhodiola crenulata functions in the liver need further clarification. The current study was designed to examine the effects of Rhodiola crenulata root extract (RCE) on hepatic glucose production. Human hepatoma HepG2 cells were treated with RCE for 6 h. Glucose production, the expression level of p-AMPK, and the expression of key gluconeogenic genes were measured. The effects of RCE were also studied in Sprague-Dawley (SD) rats. The efficacy and underlying mechanism of RCE in the liver were examined. RCE significantly suppressed glucose production and gluconeogenic gene expression in HepG2 cells while activating the AMPK signaling pathway. Interestingly, RCE-suppressed hepatic gluconeogenesis was eliminated by an AMPK-specific inhibitor, but not by the PI3K/AKT-specific inhibitor. In addition, oral administration of RCE significantly increased phosphorylated AMPK levels and inhibited gluconeogenic gene expression in the rat liver. Furthermore, RCE treatment also decreased plasma glucose concentration in rats. We present in vitro and in vivo evidence that RCE might exert the glucose-lowering effect partly by inhibiting hepatic gluconeogenesis through activating the AMPK signaling pathway. These findings provide evidence that Rhodiola crenulata may be helpful for the management of type II diabetes.


Assessment of uranium concentration in blood of Iraqi females diagnosed with breast cancer.
Cancer is a widespread significant health problem in Iraq and contributes 11% to total deaths. Throughout the Gulf Wars of 1991 and 2003, about 1200 tons of ammunition were dropped around Iraq. After the wars, cancer incidence in Iraq is about 7,000 to 8,000 cancers cases per year, and the overall incidence of lymphoma, leukemia, breast cancer, and lung cancer has increased twofold and even tripled, as compared to the time before the wars. This increase could result from environmental pollution with radioactive materials including uranium, as cancer can be caused by ionizing radiation. To investigate this hypothesis, uranium concentration in the blood of 64 Iraqi females has been measured by means of CR-39 track etch detectors (42 blood samples collected from females diagnosed with breast cancer and 22 blood samples from females without breast cancer). The results show that the uranium concentrations ranged from 19.1 ± 0.3 to 238.4 ± 0.4 with an average value of 94.9 ± 5.0 ng L-1 in the blood of women with breast cancer and from 5.2 ± 0.2 to 18.7 ± 0.04 with an average value of 10.5 ± 0.1 ng L-1 in the blood of women without breast cancer. In comparison with the literature data, elevated levels of uranium concentration were recorded in both groups, and significantly higher average uranium concentrations were found in the blood of women with breast cancer as compared to those in the blood samples of women without breast cancer. It is concluded that there is a correlation between the incidence of breast cancer in Iraqi women and elevated levels of uranium concentrations in their blood. Whether this is a casual relationship is unclear, because cancer can be caused by various carcinogens, including environmental pollution in the region.


The environmental monitoring of air pollution in the Santa Cruz industrial district of Rio de Janeiro using a plant fertility model.
In 2010, a steel company was established in Santa Cruz, Rio de Janeiro. In 2012, silver rain raised concerns about human and environmental impacts. In 2013, the steel company signed an Adjustment of Conduct Term (ACT). To evaluate air pollution in the vicinity of the steel company based on a plant fertility assay before and after ACT implementation. A pollen abortion assay was implemented using flower buds of Bauhinia forficata in 2013 and Delonix regia in 2015. Sites over 5 km from the steel company, highways, and tunnels were classified as unexposed; sites 5 km from highway/tunnel were classified as exposed to other sources; and sites 5 km from the steel company were classified as exposed. Random plant collection occurred during the dry and rainy seasons (10 buds/site and 300 cells/slide). Aborted grains were analyzed using a 400-fold magnification microscope. Statistical analyses were considered significant at the 5% level. In 2013 were collected flower buds in 27 sites (2 unexposed, 18 highway/tunnel-exposed, and 7 steel company-exposed); and 34 sites in 2015 (14 unexposed, 18highway/tunnel-exposed, and 2 steel company-exposed). In both years, the mean pollen abortion was significantly higher in the dry season for sites exposed to highway/tunnel (p < 0.001) and the steel company (p = 0.005). In 2013, the mean pollen abortion was significantly higher in sites exposed to highway/tunnel compared to unexposed sites (p = 0.004) and in sites exposed to the steel company compared to sites exposed to highway/tunnel (p = 0.034). In 2015, compared to unexposed sites, the mean pollen abortion was significantly higher in sites exposed to highway/tunnel (p = 0.014) and the steel company (p < 0.001). Overall, compared to unexposed sites, the mean pollen abortion was 5.79-fold higher in sites exposed to the steel company and 4.08-fold higher in sites exposed to highway/tunnel. Compared to unexposed plants, greater air pollution effects occurred in plants exposed to the steel company before (2013) and after (2015)ACT implementation.


Perturbations in polar lipids, starvation survival and reproduction following exposure to unsaturated fatty acids or environmental toxicants in Daphnia magna.
Acclimating to toxicant stress is energy expensive. In laboratory toxicology tests dietary conditions are ideal, but not in natural environments where nutrient resources vary in quality and quantity. We compared the effects of additional lipid resources, docosahexaenoic acid (n-3; DHA) or linoleic acid (n-6; LA), or the effects of the toxicants, atrazine or triclosan on post-treatment starvation survival, reproduction, and lipid profiles. Chemical exposure prior to starvation had chemical-specific effects as DHA showed moderately beneficial effects on starvation survival and all of the other chemicals showed adverse effects on either survival or reproduction. Surprisingly, pre-exposure to triclosan inhibits adult maturation and in turn completely blocks reproduction during the starvation phase. The two HR96 activators tested, atrazine and LA adversely reduce post-reproduction survival 70% during starvation and in turn show poor fecundity. DHA and LA show distinctly different lipid profiles as DHA primarily increases the percentage of large (>37 carbon) phosphatidylcholine (PC) species and LA primarily increases the percentage of smaller (<37 carbon) PC species. The toxicants atrazine and triclosan moderately perturb a large number of different phospholipids including several phosphatidylethanolamine species. Some of these polar lipid species may be biomarkers for diets rich in specific fatty acids or toxicant classes. Overall our data demonstrates that toxicants can perturb lipid utilization and storage in daphnids in a chemical specific manner, and different chemicals can produce distinct polar lipid profiles. In summary, biological effects caused by fatty acids and toxicants are associated with changes in the production and use of lipids.


Fatal intrapartum pulmonary embolus during tocolysis.
Intrapartum pulmonary embolus, especially in association with hypercapnea, is an extremely dangerous situation requiring immediate detection and aggressive management. The predisposing factors of obesity and bed rest must be assessed, with strong consideration given to the use of prophylactic heparin.


Prevalence of sudden cardiac death during competitive sports activities in Minnesota high school athletes.
Reliable prevalence data would be useful in assessing the impact of sudden cardiac death in young competitive athletes on the community and designing effective preparticipation screening strategies. The frequency with which these catastrophes occur is largely unknown. We utilized a circumstance unique to Minnesota in which the precise number of participants and deaths due to cardiovascular disease could be ascertained over a substantial period of time based on a long-standing insurance program for catastrophic injury or death, mandatory for all student athletes engaged in interscholastic sports. Over the 12-year period, 1985/1986 to 1996/1997, inclusive, three sudden deaths due to cardiovascular disease occurred in competitive high school athletes (grades 10-12) during competition or practice. At autopsy, 1 each proved to be due to anomalous origin of the left main coronary artery from the right sinus of Valsalva, congenital aortic valve stenosis (with bicuspid valve) and myocarditis. All three athletes were white and male, 16 or 17 years of age; two competed in cross-country/track and one in basketball. During the study period there were 1,453,280 overall sports participations and 651,695 student athlete participants among the 27 high school sports. The calculated risk for sudden death was 1:500,000 participations and 1:217,400 participants per academic year (or 0.46/100,000, annually). Over a 3-year high school career for a student athlete the estimated risk was 1:72,500. The risk of sudden cardiac death in a population of high school student athletes was small, in the range of one in 200,000 per year, and was higher in male athletes. The rare occurrence of sudden cardiac death in competitive sports underlines the limitations implicit in structuring productive and cost-effective broad-based preparticipation screening strategies for high school athletes.


A framework for intracranial aneurysm detection and rupture analysis on DSA.
Intracranial aneurysm is a severe cerebrovascular disease that can result in subarachnoid hemorrhage (SAH), leading to high incidence and mortality rates. Computer-aided detection of aneurysms can assist doctors in enhancing diagnostic accuracy. The analysis of aneurysm imaging holds considerable predictive value for aneurysm rupture. This paper presents a method for the detection of aneurysms and analysis of ruptures using digital subtraction angiography (DSA). A total of 263 aneurysms were analyzed, with 125 being ruptured and 138 being unruptured. Firstly, a filter based on the eigenvalues of the Hessian matrix was proposed for aneurysm detection. The filter's detection parameters can be automatically obtained through Bayesian optimization. Aneurysms were detected based on their structure and the response of the filter. Secondly, considering the variations in blood flow and morphology among aneurysms in DSA, intensity, texture, and blood perfusion features were extracted from the ruptured aneurysms and unruptured aneurysms. Subsequently, a sparse representation (SR) method was utilized to classify unruptured and ruptured aneurysms. The experimental results for aneurysm detection showed that the F1-score was 94.1%. In the classification of ruptured and unruptured aneurysms, the accuracy, sensitivity, specificity, and area under curve (AUC) were 96.1%, 94.4%, 97.5%, and 0.982, respectively. This paper presents a scheme combining an aneurysm detection filter and machine learning, offering a reliable solution for the diagnosis and prediction of aneurysm rupture.


Effectiveness and complications of anthracycline and taxane in the therapy of breast cancer: a meta-analysis.
To compare the efficacy and safety between anthracycline & taxane and anthracycline in the treatment of breast cancer. Computer-assisted literature search was performed with PubMed, MEDLINE, EMBASE and Cochrane Controlled Trials Register (CCTR) to identify pertinent literatures. Software RevMan 5.0 was used for statistical analysis. The measurement of interest outcomes included severe neurotoxicity, death without breast cancer recurrences, leukemia, venous thrombus and severe cardiotoxicity. A total of 10 randomized controlled trial studies (RCTs) containing 18,198 cases were selected in this meta-analysis. Of which, 9,902 cases were treated with anthracycline & taxane and 8,296 cases treated with anthracycline alone as control. Anthracycline & taxane showed lower risks of incident leukemia (RR = 0.40; 95% CI: 0.18, 0.90), venous thrombus (RR = 0.49; 95% CI: 0.29, 0.84) and severe cardiotoxicity (RR = 0.41, 95%CI: 0.26, 0.66), but higher risks of incident severe neurotoxicity (RR = 5.97; 95% CI: 1.72, 20.65) and non-recurrent death (RR = 1.79; 95% CI: 1.06, 3.04), compared to anthracycline alone. Clinically important differences exist for general safety in favour of the anthracycline & taxane rather than anthracycline alone. However, as a result of tumor recurrent rate, anthracycline might be superior to anthracycline & taxane. A longer duration of follow-up and a larger number of cases are required to better assess the efficacy and safety profile of the treatment of breast cancer.


Cooperative binding of DctD to the dctA upstream activation sequence of Rhizobium meliloti is enhanced in a constitutively active truncated mutant.
DctD, a sigma54-dependent, two-component regulator, binds to promoter distal (A) and promoter proximal (B) sites in an activation sequence located upstream of the dctA promoter. We report gel filtration and quantitative DNase I footprint experiments supporting a model in which DctD2 binds to these sites cooperatively. The global analysis of upstream activation sequences containing sites A and B, A and B one-half helical turn out of phase, and only B yielded values for the intrinsic and cooperative binding free energies of DeltaG0A = -9.5 +/- 0.3, DeltaG0B = -11.2 +/- 0.2, and DeltaG0AB = -2.5 +/- 0.5. A separate analysis of data from upstream activation sequences containing site A and a point mutant of site B, and site A and mutant site B one-half helical turn out of phase confirmed the estimate of cooperativity, yielding free energy values of DeltaG0A = -9.4 +/- 0.2, DeltaG0B(G-->C) = -10.0 +/- 0.2, and DeltaG0AB(G-->C) = -2.2 +/- 0.4. We previously showed that removing the two-component receiver domain from DctD, making DctDDelta(1-142), yields a constitutively active truncated protein. Global analysis of binding data for DctDDelta(1-142) showed that this constitutively active mutant has intrinsic binding energies equal to that of the inactive DctD protein, but that it displays significantly higher cooperativity (DeltaG0A = -9.4 +/- 0.6, DeltaG0B = -11.1 +/- 0.3, and DeltaG0AB = -3.8 +/- 0.6.).


Sphingomyelin synthase 2 over-expression induces expression of aortic inflammatory biomarkers and decreases circulating EPCs in ApoE KO mice.
This study sought to assess the effect of sphingomyelin synthase 2 (SMS2) over-expression on plaque component and endothelial dysfunction in atherosclerosis. We generated recombinant adenovirus vectors containing human SMS2 cDNA (AdV-SMS2) or control gene GFP cDNA (AdV-GFP). Both AdVs were injected (i.v.) into ApoE KO mice to establish SMS2 over-expressing and control mice models, respectively. The mice were fed a high fat diet for 30 days. We then examined their plasma lipid levels, expression levels of aortic inflammatory biomarkers critical for the plaque's stability, and numbers of peripheral endothelial progenitor cells (EPC). Compared with the control mice, SMS2 over-expression had significantly (1) increased aortic matrix metalloproteinase-2 (MMP-2), monocyte chemoattractant protein-1 (MCP-1), tissue factor (TF) and cyclooxygenase-2 (COX-2) mRNA levels (1.9-fold, 2.2-fold, 2.6-fold and 3.2-fold, respectively, P<0.01) and protein levels (2.2-fold, 1.9-fold, 1.9-fold and 2.1-fold, respectively, P<0.01); (2) increased MMP-2, COX-2 in situ expression in aortic root (2.6-fold and 2.3-fold, respectively, P<0.01); (3) decreased aortic COX-1 mRNA levels (65%, P<0.01) and protein levels (64%, P<0.01); and (4) decreased CD34/KDR-positive cells (33%, P<0.01), circulating angiogenic cells (CACs) (50%, P<0.05), and colony forming units (CFUs) (40%, P<0.05) in circulation. SMS2 over-expression was probably associated with increased expression of aortic inflammatory biomarkers, as well as decreased numbers of CD34/KDR-positive cells, CACs and CFUs in circulation. Therefore, SMS2 over-expression might correlate with endothelial dysfunction and aggravate atherosclerotic plaque instability in ApoE KO mice.


Comparison between percutaneous transthoracic co-axial needle CT-guided biopsy and transbronchial lung biopsy for the diagnosis of persistent pulmonary consolidation.
Diagnosing persistent pulmonary consolidation still faces challenges. The purpose of this study is to compare the diagnostic yield and the complication rate between percutaneous transthoracic CT-guided coaxial needle biopsy (PTCNB) and transbronchial lung biopsy (TBLB) of persistent pulmonary consolidation. From January 1, 2016, to December 31, 2020, we have retrospectively enrolled a total of 155 consecutive patients (95 males, 60 females) with persistent pulmonary consolidation who underwent both TBLB and PTCNB. According to the standard reference, the diagnostic yield, accuracy, sensitivity and specificity of PTCNB and TBLB were assessed and compared. According to the standard reference, the final biopsy diagnoses of 11 cases were confirmed true malignant based on the surgical resections, the remaining were confirmed by clinical and imaging follow-up for at least 12 months. The overall diagnostic accuracy, sensitivity and specificity of PTCNB for malignant diagnosis were 91.61%, 72.34% and 100%, whereas of TBLB were 87.74%, 59.57% and 100%. The diagnostic yield of PTCNB and TBLB were 50.32% and 25.16%, respectively. For the TBLB-based negative cases, PTCNB provided a definite diagnostic yield of 37.93%. There were 45 (29.03%), 22 (14.19%) and 13 (8.39%) patients who experienced pneumothorax, intrapulmonary hemorrhage and hemoptysis, respectively, in PTCNB, while there were only 5 (3.22%) cases of mild intraprocedural bleeding occurring in TBLB. CT-guided co-axial needle biopsy is an effective and safe modality, associated with higher diagnostic yield and better diagnostic accuracy compared to transbronchial lung biopsy for malignancy presenting as persistent consolidation, especially as the complementary method for TBLB-based negative lung lesions. Both PTCNB and TBLB showed high diagnostic accuracy for malignancy. PTCNB had a higher diagnostic yield than TBLB for persistent pulmonary consolidation. PTCNB could provide a complementary diagnosis for TBLB-based negative lung consolidation.


Aztreonam in the treatment of urinary tract infection.
The possible advantages of the monobactam antibiotic aztreonam in the treatment of hospital-acquired urinary tract infection were assessed in a study comparing aztreonam (0.5 to 1 g twice daily or three times daily) to cefamandole (1 g three times daily) in 159 patients. Initial pathogens were eradicated in 91.7 percent of the patients of the aztreonam group who were treated three times daily, in 82.7 percent of the group treated twice daily, and in 78.3 percent of the patients receiving cefamandole. Reinfection and superinfection were most commonly caused by enterococci in the aztreonam groups and by Pseudomonas aeruginosa in the cefamandole group. In a second study, 35 patients infected with organisms resistant to other antibiotics were treated with aztreonam 1 to 6 g per day for eight days. The overall cure rates were 93 percent for Pseudomonas infections, 87.5 percent for Escherichia coli infections, and 100 percent for other pathogens.


Advances in mechanisms and engineering of electroactive biofilms.
Electroactive biofilms (EABs) are electroactive microorganisms (EAMs) encased in conductive polymers that are secreted by EAMs and formed by the accumulation and cross-linking of extracellular polysaccharides, proteins, nucleic acids, lipids, and other components. EABs are present in the form of multicellular aggregates and play a crucial role in bioelectrochemical systems (BESs) for diverse applications, including biosensors, microbial fuel cells for renewable bioelectricity production and remediation of wastewaters, and microbial electrosynthesis of valuable chemicals. However, naturally occurred EABs are severely limited owing to their low electrical conductivity that seriously restrict the electron transfer efficiency and practical applications. In the recent decade, synthetic biology strategies have been adopted to elucidate the regulatory mechanisms of EABs, and to enhance the formation and electrical conductivity of EABs. Based on the formation of EABs and extracellular electron transfer (EET) mechanisms, the synthetic biology-based engineering strategies of EABs are summarized and reviewed as follows: (i) Engineering the structural components of EABs, including strengthening the synthesis and secretion of structural elements such as polysaccharides, eDNA, and structural proteins, to improve the formation of biofilms; (ii) Enhancing the electron transfer efficiency of EAMs, including optimizing the distribution of c-type cytochromes and conducting nanowire assembly to promote contact-based EET, and enhancing electron shuttles' biosynthesis and secretion to promote shuttle-mediated EET; (iii) Incorporating intracellular signaling molecules in EAMs, including quorum sensing systems, secondary messenger systems, and global regulatory systems, to increase the electron transfer flux in EABs. This review lays a foundation for the design and construction of EABs for diverse BESs applications.


Racism and Stress-Related Growth Among Asian Internationals: Ethnic Identity, Resilience, and Coping During COVID-19.
Experiences of anti-Asian discrimination following COVID-19 has deleterious effects on the mental health of Asian internationals residing in the United States. In this study, hierarchical regression models and Hayes' PROCESS models were used to examine the main effect and moderating effect of ethnic identity, coping strategy, and resilience on stress-related growth among Asian international students and workers (N = 237) in the United States who experienced racism during the pandemic. The findings indicated coping strategies and resilience were significantly associated with stress-related growth. Ethnic identity and coping strategies additionally moderated the link between the experience of racism and stress-related growth.


Immune derangement in patients with malignant melanoma.
The interaction between immune system and growing tumor can be expressed differently at different stages of the disease. This presentation covers three facets of these reactions in melanoma patients. A. The Primary Tumor. Time-lapse cinematography, with an analysis of lymphocyte movement demonstrated positive and negative chemotaxis against tumor tissues which correlated with their histological presence or absence within the primary tumor. B. The Regional Lymph Nodes. Histological examination of regional lymph nodes showed an increase in germinal center activity and B cell number, with a decrease in sinus histiocytosis and monocyte count as the tumor progressively invaded the node. This correlated with the elution studies, wherein the antimembrane antibody decreased and the anti-cytoplasmic antibody increased during the same period of progression. C. Humoral Immunity and Metastasis. Clinical metastasis heralded the decrease of anti-membrane antibodies with a rise in anti-immunoglobulins, especially anti-idiotypic antibodies and immune complexes containing tumor-directed antibody and either antigen or anti-immunoglobulin. This triad of anti-immunoglobulin, immune complexes and anergy as seen in other diseases with persistent antigenic stimulation, results in abnormal regulation and derangement.


Removal of protruding screws in a painful total hip arthroplasty: A case report.
Persistent pain after total hip arthroplasty can be challenging for the orthopedic surgeon. We present a case of a 56-year-old female with an uncommon cause of persistent pain after total hip replacement, due to protruding screws with the subsequent impingement of surrounding soft tissues. The patient presented persistent groin pain after total hip revision surgery. After ruling out infection and loosening, an infiltration of iliopsoas muscle was performed, with only temporary improvement. The magnetic resonance depicted the conflict of the screws with the surrounding soft tissues, in close relation to the iliopsoas muscle, the external obturator muscle and the sciatic nerve. Revision surgery was performed, removing the screws, and implanting a new liner with complete remission of symptoms. Our case presents an atypical cause of pain due to surrounding tissue lesions by offending screws with complete resolution after only screw removal. In the clinical study of persistent pain following a total hip replacement, screws length, and protrusion should be considered and ruled out as a possible and treatable etiology. Removal of the screws after cup integration can be a conservative and effective strategy to treat the pain.


Combined sunitinib and radiation therapy for preoperative treatment of soft tissue sarcoma: results of a phase I trial of the German interdisciplinary sarcoma group (GISG-03).
Experimental data demonstrated that concurrent anti-angiogenic treatment with sunitinib may improve the efficacy of radiation therapy (RT). Here we report the results of a phase I trial performed within the German Interdisciplinary Sarcoma Group (GISG-03) of combined sunitinib and RT for neoadjuvant treatment of locally advanced soft tissue sarcoma (STS). The primary endpoint of the study was to explore the recommended dose of sunitinib combined with RT for subsequent trials. Treatment response, postoperative complications after tumor resection and toxicity according to CTCAE 4.0 were secondary endpoints. The study used a 3 + 3 design. Patients received either 25 mg (dose level 1) or 37.5 mg (dose level 2) sunitinib two weeks prior to and throughout RT (28 × 1.8 Gy). Surgery was scheduled 5-8 weeks after completion of neoadjuvant treatment. NCT01498835. Six patients were enrolled in dose level 1 and three patients in dose level 2. Median tumor size was 11 cm. Tumors were located in the retroperitoneum (4/9), lower leg (3/9) or trunk (2/9). At dose level 1, 1/6 patients developed dose limiting lymphopenia. At dose level 2, no patient developed dose limiting toxicity. Most frequent toxicities were hematological (8/9) and oral (5/9). Dose adjustments of sunitinib were necessary in 5/9 patients. All patients received full dose RT and underwent tumor resection (8/9 R0 and 1/9 R1). Local toxicity of RT did not exceed Grade 2. 2/9 patients had postoperative complications requiring re-intervention. Treatment response according to RECIST was as follows: partial response 1/9, stable disease 7/9, and progressive disease 1/9. Pathological examination revealed ≥ 95 % tumor necrosis in 3/9 resected specimens. Combined sunitinib and RT was tolerable as neoadjuvant treatment for locally advanced STS patients regardless of tumor localization. The recommended sunitinib dose for subsequent trials is 37.5 mg.


Distribution and characterization of motilin receptors in the cat.
We demonstrate binding of [125I][Nle13-po]motilin to homogenates of cat gastric and small intestinal, but not to colonic smooth muscle tissue. The density was (Bmax in fmol/mg protein): 0 (fundus); 12 +/- 2 (corpus); 22 +/- 3 (antrum); 55 +/- 12 (duodenum); 44 +/- 10 (jejunum); 17 +/- 1 (ileum); 0 (colon). A significant (p < 0.05) difference was found between the dissociation constant for motilin in the stomach (pKd = 8.84 +/- 0.06) and in the small intestine (pKd = 8.58 +/- 0.08). The motilides erythromycin-A (EM-A), EM-523, and EM-A N-oxide displaced labeled [Nle13-po]motilin bound to cat duodenal receptor with potencies (pKd) of 5.47 +/- 0.23, 7.60 +/- 0.24, and < 4.3, respectively. Studies with [Leu13-po]motilin fragments showed that the N-terminus of motilin interacts with the receptor. In the tissue bath, duodenal strips mounted in the longitudinal direction responded to motilin, EM-523, and EM-A (pEC50: 8.29 +/- 0.08; 7.12 +/- 0.12; 5.99 +/- 0.15). The compounds had a comparable intrinsic activity (83 +/- 3%; 80 +/- 5%; 82 +/- 5% of the response to ACh), which was unaffected by atropine, TTX, hexamethonium, and zacopride but reduced by verapamil and calcium-free medium. Cat stomach and small intestine possess smooth muscle motilin receptors, which have comparable properties as those found in man and in rabbit.


Antithyroid antibody-linked symptoms in borderline personality disorder.
Circulating thyroid autoantibodies are more prevalent in patients with mood disorders than in the general population, but longitudinal clinical data that establish a relationship between thyroid antibody status and the course of any psychiatric syndrome have been lacking. In addition, scant attention has been paid to thyroid hormones and autoimmunity in borderline personality disorder (BPD). We report a case of a patient with classic BPD whose fluctuating mood and, especially, psychotic symptoms-rated using a double-blind method-were directly linked to antithyroglobulin antibody titers serially determined over an inpatient period of 275 d. Significantly lower psychosis and depression ratings were seen during a 4-wk period of relatively low antithyroid antibody titers, during blinded treatment with carbamazepine, than were observed during two high autoantibody epochs. The significant positive correlations between nurse- and patient-rated depression and thyroid autoantibodies over the entire period of inpatient study were similar to those also observed between urinary free cortisol levels and depression; the positive correlation between antithyroglubulin antibody titers and psychotic symptoms was stronger (r = +0.544; p < 0.002). Although this patient had biochemical indices of primary hypothyroidism, she showed only marginal improvement to triiodothyronine (T3) and no apparent clinical response to sustained levorotatory thyroxine (T4) administration; neither were antithyroid antibody titers significantly associated with changes in T3, free T4, or thyroid-stimulating hormone concentrations. She clinically deteriorated during a 50-d fluoxetine trial. The present data demonstrate a clinically significant, longitudinal correlation between fluctuating antithyroid antibody titers and symptoms of borderline psychopathology in our patient. It will be of interest to determine the prevalence, pathophysiologic mechanisms, and treatment implications of this putative autoimmune- BPD link.


Synergic effect of global thermal anomalies and local dredging activities on coral reefs of the Maldives.
We investigated possible synergic effects on coral reefs of the local land reclamation activities in the Himmafushi Island (North Malè atoll, Maldives) and the global bleaching event that affected the Maldives in 2016. A BACI (Before-After Control-Impact) sampling design was adopted to contrast effects of dredging activities before and after the occurrence of both dredging and bleaching. The Reef Check protocol, a standardised and worldwide survey method, was applied to collect data through underwater visual surveys on corals, macro-zoobenthos, and fish communities. The bleaching in 2016 hit all the reefs investigated, but only in the reefs around Himmafushi (i.e., the impact sites) the live hard coral reduced significantly its cover and the sand deposited on reefs showed a fourfold increase. Substrate indicators (i.e., coral community and abiotic components) turned out to be more effective than macro-zoobenthos and fish in this short-term environmental impact study.


Distribution of capsaicin-sensitive nerve fibres containing immunoreactive substance P in cutaneous and visceral tissues of the rat.
Treatment of newborn rats with capsaicin causes a selective and permanent degeneration of unmyelinated sensory fibres, some of which contain immunoreactive substance P (ISP). Following treatment of newborn rats with capsaicin (50 mg/kg), the ISP content was decreased by 66-75% in various skin areas and in the oral and nasal mucosae as measured at the age of 3-4 months. There was no significant depletion of ISP in the mucosa of the tongue. The ISP content of trachea, lungs, myocardium, hepatic duct, ureter and urinary bladder, was decreased by 60-84%. The ISP concentrations in stellate and mesenteric ganglia were reduced by 54 and 81%, respectively. These results indicate a widespread innervation of cutaneous and visceral tissues by sensory nerve fibers containing ISP.


Simple protein purification through affinity adsorption on regenerated amorphous cellulose followed by intein self-cleavage.
A simple, low-cost, and scalable protein purification method was developed by using a biodegradable regenerated amorphous cellulose (RAC) with a binding capacity of up to 365 mg protein per gram of RAC. The recombinant protein with a cellulose-binding module (CBM) tag can be specifically adsorbed by RAC. In order to avoid using costly protease and simplify purification process, a self-cleavage intein was introduced between CBM and target protein. The cleaved target protein can be liberated from the surface of RAC by intein self-cleavage occurring through a pH change from 8.0 to 6.5. Four recombinant proteins (green fluorescence protein, phosphoglucomutase, cellobiose phosphorylase, and glucan phosphorylase) have been purified successfully.


Resveratrol and its nanocrystals: A promising approach for cancer therapy?
There has been a significant research interest in nanocrystals as a promising technology for improving the therapeutic efficacy of poorly water-soluble drugs, such as resveratrol. Little is known about the interaction of nanocrystals with biological tissue. The aim of this study was to investigate the potential use of resveratrol (RSV) and its nanocrystals (NANO-RSV) as antitumor agents in Ehrlich ascites tumour (EAT)-bearing mice and the interaction of nanocrystals with biological tissue through biochemical and histological changes of kidney, liver and EAT cells. After intraperitoneal injection of 2.5 × 106 cells into the abdominal cavity of mice, treatment of animals was started next day by injecting RSV or NANO-RSV at a dose of either 25 or 50 mg/kg every other day for 14 days. The results show that the administration of resveratrol and its nanocrystals lead to significant reductions in the proliferation of tumour cells in the abdominal cavity, and a reduction of the number of blood vessels in the peritoneum, with low systemic toxicity. In histopathological examinations, greater hepatocellular necrosis and apoptosis, hepatic fibrosis around the central vein and degeneration with minor fatty change were observed with RSV than with NANO-RSV. Inflammation with proximal tubular necrosis and renal glomerulus swelling were also observed, together with slight elevation of several biochemical parameters in both the RSV and NANO-RSV groups. In order to increase the beneficial effects and reduce risks associated with resveratrol nanocrystals, additional factors such as dose, genetic factors, health status, and the nature of the target cells should also be considered.


The influence of nicotine pretreatment on mesoaccumbens dopamine overflow and locomotor responses to D-amphetamine.
Pretreatment with psychostimulant drugs causes sensitisation of their effects on locomotor activity and dopamine (DA) overflow in the nucleus accumbens (NAcc) and there is evidence for similarities in the mechanisms involved. This study used in vivo microdialysis in conscious freely moving rats to investigate the extent to which pretreatment with nicotine causes sensitisation to D-amphetamine. Pretreatment with nicotine (0.4 mg/kg s.c. daily for 5 days) caused sensitisation of the locomotor responses to D-amphetamine (0.1-0.5 mg/kg s.c.) but not cocaine (15 mg/kg i.p.). Nicotine pretreatment did not influence the increase in DA overflow into dialysis probes, located in the core of the NAcc, evoked by systemic injections of D-amphetamine or cocaine (15 mg/kg i.p.) but decreased the overflow evoked by the administration of D-amphetamine (1 x 10(-6) M) through the dialysis probe. The results provide further evidence for a dissociation between the expression of sensitised locomotor responses to psychostimulant drugs and sensitisation of their stimulatory effects on DA overflow in the core of the NAcc. The results suggest that the sensitisation of the effects of nicotine on DA overflow in this subdivision of the NAcc may be pharmacologically specific to nicotinic drugs.


Impact of pain and remission in the functioning of patients with depression in Mainland China, Taiwan, and Hong Kong.
The present study analyzes functioning during the course of treatment of a major depressive disorder in Mainland China, Taiwan, and Hong Kong. Data in this post hoc analysis were taken from a 24-week prospective, observational study in 12 countries worldwide. Of these, 422 patients were included from Mainland China (N = 205; 48.6%), Taiwan (N = 199; 47.2%), and Hong Kong (N = 18; 4.2%). Functioning was measured with the Sheehan Disability Scale, pain with the Somatic Symptom Inventory, and depression severity with the Quick Inventory of Depressive Symptomatology Self Report 16. Patients were classified as having no pain, persistent pain, or remitted pain. A mixed model with repeated measures was fitted to analyze the relationship between pain and functioning, adjusting for severity and other factors. At baseline, 40% of the patients had painful physical symptoms. At 24 weeks, 6% of the patients had persistent pain. Sixty percent of the patients achieved remission. Patients with pain had a higher severity of depression score and lower functioning (P < .05) at baseline. At 24 weeks, patients with persistent pain had lower functioning (P < .05). The regression model found that clinical remission was associated with higher functioning at endpoint and that patients with persistent pain had lower functioning at endpoint when compared with the no-pain group. Patients presenting with pain had lower functioning at baseline. At 24 weeks, pain persistence was associated with significantly lower functioning as measured by the Sheehan Disability Scale. Clinical remission was associated with better functional outcomes. The course of pain was related to achieving remission.


The influence of coincidental vascular pathology on symptomatology and course of Alzheimer's disease.
The aim of this review is to determine the influence of coincidental cerebrovascular pathology on the symptomatology and course of Alzheimer's disease (AD). The link between stroke and AD is probably higher than expected by chance for the following reasons: (i) both pathologies share genetic risk factors such as the epsilon 4 allele of the apolipoprotein E gene; (ii) AD patients have changes in the brain vessels that may lead to either ischemic or hemorrhagic stroke or white matter changes or both; (iii) there is evidence of an increased risk of stroke in AD patients; (iv) there is evidence of a frequent association of AD and stroke at autopsy. Because of the summation of the various types of lesions, stroke lesions may lead to an increase progression of cognitive decline in AD patients. Recognition of a vascular component in a dementia syndrome is therefore useful for the management of AD patients. Whether an optimal management of risk factors for stroke may delay the clinical expression of dementia in patients with preclinical Alzheimer pathology should be evaluated.


Cost-effectiveness of HIV screening of pregnant women in hospitals of the Paris area. The Paris-Tours study group of antenatal transmission of HIV, Group '9 maternites'.
In the context of an epidemiologic multicentric study about perinatal transmission of HIV, screening was systematically proposed to all pregnant women attending nine maternities clinics of the Paris region (n = 7600, between August 1987 and July 1988) at their first prenatal visit. Among them, 2145 had already been tested and 45 were known to be HIV positive. So, 5660 tests were performed during the first 6 months (period 1), and 17 pregnant women were discovered to be positive. The total cost of screening has been estimated between FF. 720,000 and 775,000, resulting in a mean cost per pregnant woman found to be HIV positive of about FF. 42,000 to 45,000. A similar calculation over the following 5 months (period 2) gave a mean cost of between FF. 165,000 and 178,000. Since the women, before being screened, had to answer a short questionnaire about risk factors; cost and effectiveness of a selective screening strategy could be simulated. The preference of systematic screening to selective screening enabled the discovery of two HIV positive cases in each period, the marginal cost, i.e., cost per extra pregnant woman found to be HIV positive was thus FF. 303,320 to 327,540 for period 1, and FF. 572,240 to 619,000 for period 2. Although these figures seem high, an estimation of the cost-effectiveness does not allow us to conclude whether it is in society's interest to devote the funds necessary to move away from selective screening towards systematic screening.(ABSTRACT TRUNCATED AT 250 WORDS)


Radiation exposure to the hands from mini C-arm fluoroscopy.
To quantify the level of radiation exposure to the hands of hand surgeons using intraoperative mini C-arm fluoroscopy and to compare the actual level of exposure with predicted levels and acceptable limits. Five hand surgeons were given ring dosimeters to measure radiation exposure to their hands during surgery of the finger, hand, and wrist. A total of 81 rings were analyzed. After the clinical study a phantom was used to measure scatter at close range from the mini C-arm. Surgeons' hands were exposed to an average +/- SD of 20 +/- 12.3 mrem/case. For comparison a chest x-ray results in approximately 20 mrem exposure to the patient. Radiation exposure for the group of hand surgeons ranged from 5 to 80 mrem. Surgeons used an average of 51 +/- 36.9 seconds of fluoroscopy time per case. Exposure time for the group ranged from 6 to 170 seconds. The radiation scatter rate decreases precipitously outside the beam or beyond the radius of the intensifier. An average exposure to the hands of 20 mrem/case suggests that surgeons' hands must be entering the beam and getting direct exposure. Hand surgeons work close to the beam and as a result their hands potentially are exposed to a nontrivial amount of radiation. We recommend that surgeons who use the mini C-arm use precautions to minimize radiation exposure, particularly to their hands.


Functional properties and substrate characterization of human CYP26A1, CYP26B1, and CYP26C1 expressed by recombinant baculovirus in insect cells.
The cytochrome P450 CYP26 family of retinoic acid (RA) metabolizing enzymes, comprising CYP26A1, CYP26B1, and CYP26C1 is critical for establishing patterns of RA distribution during embryonic development and retinoid homeostasis in the adult. All three members of this family can metabolize all trans-RA. CYP26C1 has also been shown to efficiently metabolize the 9-cis isomer of RA. We have co-expressed each of the CYP26 enzymes along with the NADPH-cytochrome P450 oxidoreductase using a baculovirus/Sf9 insect cell expression system to determine the enzymatic activities of these enzymes in cell free preparations and have established an in vitro binding assay to permit comparison of binding affinities of the three CYP26 enzymes. We demonstrated that the expressed enzymes can efficiently coordinate heme, as verified by spectral-difference analysis. All CYP26s efficiently metabolized all-trans-RA to polar aqueous-soluble metabolites, and in competition experiments exhibited IC(50) values of 16, 27, and 15nM for CYP26A1, B1, and C1 respectively for all-trans-RA. Furthermore, this metabolism was blocked with the CYP inhibitor ketoconazole. CYP26C1 metabolism of all trans-RA could also be effectively competed with 9-cis RA, with IC(50) of 62nM, and was sensitive to ketoconazole inhibition. CYP26 enzymes are functionally expressed in microsomal fractions of insect cells and stably bind radiolabeled RA isomers with affinities respecting their substrate specificities. We demonstrated that compared to CYP26A and CYP26B, only CYP26C1 was able to bind with high affinity to 9-cis-RA. These assays will be useful for the screening of synthetic substrates and inhibitors of CYP26 enzymes and may be applicable to other cytochrome P450s and their respective substrates.


Some considerations on caloric test results.
The caloric test procedure as suggested by Fitzgerald & Hallpike is still widely used. With a carefully standardized procedure it is well suited to identify the affected side in patients with unilateral vestibular impairments. By repeated testing it is also possible to follow the course of a vestibular affection.


Primary empty sella syndrome and bipolar affective illness: case report.
This report concerns an elderly woman with primary empty sella syndrome and bipolar affective illness. She had no endocrine, visual, or neurologic dysfunction and had received electroconvulsive therapy with no long-term adverse effects. Remission of the affective illness has been maintained for five years with lithium carbonate therapy.


Effects of electroacupuncture on pediatric chronic urinary retention: a case-series study.
This study aims to preliminarily evaluate the effect and safety of electroacupuncture (EA) in treating pediatric chronic urinary retention (CUR) following lumbosacral surgeries, with treatment duration evaluated. This prospective case-series study was performed from August 5, 2017, to July 31, 2022. Pediatric patients diagnosed with CUR following lumbosacral surgeries were included and treated by EA for 2-16 weeks. Responders were defined as participants achieving a reduction of 50% or more in post void residuals (PVR) from baseline. Time-to-event analysis was applied to explore the association between EA treatment duration and response rate. Adverse event was recorded. Totally 14 participants (mean [SD] age, 12 [4] years) completed EA treatment. Response rate was 71% (10/14) at the 12th week. 50% (7/14) of participants removed catheters at the 12th week, and none of them experienced re-catheterization in the 24-week follow-up. No serious adverse event was reported. Time-to-event analysis estimated that over 50% patients could respond to EA of more than 8 weeks. Subgroup analysis showed that participants with baseline PVR ≥300 ml and CUR duration ≥12 months experienced longer EA duration to reach the response rate of 50%, compared with those whose PVR <300 ml and CUR duration <12 months (median value: 12 weeks vs. 8 weeks, 12 weeks vs. 4 weeks, respectively). EA could reduce PVR for pediatric patients suffering from CUR following lumbosacral surgeries, with long-term efficacy and safety. EA treatment of more than 8 weeks was reasonable. Further study of a larger sample and controlling is needed. www.chictr.org.cn, identifier, ChiCTR1800020222.


Self-attenuation of extreme events in Navier-Stokes turbulence.
Turbulent fluid flows are ubiquitous in nature and technology, and are mathematically described by the incompressible Navier-Stokes equations. A hallmark of turbulence is spontaneous generation of intense whirls, resulting from amplification of the fluid rotation-rate (vorticity) by its deformation-rate (strain). This interaction, encoded in the non-linearity of Navier-Stokes equations, is non-local, i.e., depends on the entire state of the flow, constituting a serious hindrance in turbulence theory and even establishing regularity of the equations. Here, we unveil a novel aspect of this interaction, by separating strain into local and non-local contributions utilizing the Biot-Savart integral of vorticity in a sphere of radius R. Analyzing highly-resolved numerical turbulent solutions to Navier-Stokes equations, we find that when vorticity becomes very large, the local strain over small R surprisingly counteracts further amplification. This uncovered self-attenuation mechanism is further shown to be connected to local Beltramization of the flow, and could provide a direction in establishing the regularity of Navier-Stokes equations.


Neuromedin B: a novel bombesin-like peptide identified in porcine spinal cord.
In our survey for unknown neuropeptides in porcine spinal cord, we have purified a novel decapeptide that exhibits a potent stimulant effect on the smooth muscle preparation of rat uterus. By microsequencing and synthesis, the peptide has been identified as Gly-Asn-Leu-Trp-Ala-Thr-Gly-His-Phe-Met-NH2. The peptide is found to have a surprising sequence homology to amphibian bombesins, and to display a potent contractile activity of rat uterus in the characteristic manner of the known bombesins. These facts strongly suggest that the peptide may be involved in the neural communication system of mammals as a neuromediator or hormone. Thus, we propose the name "neuromedin B" for the peptide.


Aortic intussusception complicating diagnostic angiography: recognition and management.
During the diagnostic evaluation of a 31-year-old male with Marfan syndrome, an acute type B aortic dissection, and rising creatinine, the retrograde loop of our selective catheter inadvertently engaged the entry tear of the dissection in the mid-descending aorta. Traction on the catheter led to a full circumferential dehiscence of the remaining lumen, causing an intimointimal intussusception down to the level of the celiac artery with complete collapse of the true lumen and visceral and renal artery obstruction. Balloon fenestration and supramesenteric stenting of the true lumen decompressed the intussuscepted intimal flap and restored normal perfusion pressures.


A rapid purification of L-glutamic acid decarboxylase from the brain of the locust Schistocerca gregaria.
L-Glutamic acid decarboxylase (GAD; EC 22.214.171.124) was purified to apparent homogeneity from the brain of the locust Schistocerca gregaria using a combination of chromatofocusing (Mono P) and gel filtration (Superose 12) media. The homogeneity of the enzyme preparation was established by native polyacrylamide gel electrophoresis (PAGE) with silver staining. The molecular weight of the purified enzyme was estimated from native gradient gel electrophoresis and gel filtration chromatography to be 97,000 +/- 4,000 and 93,000 +/- 5,000, respectively. When analysed by sodium dodecyl sulphate-PAGE, the enzyme was found to be composed of two distinct subunits of Mr 51,000 +/- 1,000 and 44,000 +/- 1,500. Tryptic peptide maps of iodinated preparations of these two subunits showed considerable homology, suggesting that the native enzyme is a dimer of closely related subunits. The purified enzyme had a pH optimum of 7.0-7.4 in 100 mM potassium phosphate buffer and an apparent Km for glutamate of 5.0 mM. The enzyme was strongly inhibited by the carbonyl-trapping reagent aminooxyacetic acid with an I50 value of 0.2 microM.


Conventional microsurgical technique and endovascular method for the treatment of cerebral aneurysms: a comparative view.
Endovascular embolization using Guglielmi Detachable Coils (GDCs) for complicated intracranial aneurysms has become widely accepted as an alternative to direct surgery. There is now a choice of therapeutic options for the management of cerebral aneurysms. The decision for treatment of an individual patient should be based on objective selection of the safest and most effective treatment. In addition, less invasive and cost effective treatment should be chosen. It is self-evident that the primary consideration in the selection process must be the immediate and long-term welfare of the individual patient, rather than the physician's preference for any specific treatment modality. GDC embolization is a less invasive and safe treatment with low incidence of periprocedural morbidity, and has been successful in preventing acute subsequent bleeding, whereas follow-up results are less satisfactory in cases involving incompletely obliterated lesions. High incidence of recanalization was promoted in cases with neck remnant and/or body filling. In contrast, the most important advantage of direct surgery is long-term durability, while conditions of patients and aneurysmal geometry limit the indication of direct surgery. In addition, direct surgery could be applied to complicated aneurysms with wide-neck or branching from the neck in combination with vascular reconstruction technique, such as EC-IC bypass. With these limitations in mind, patients need to be very carefully chosen for GDC embolization or direct surgery.


Reactive oxygen species, vascular Noxs, and hypertension: focus on translational and clinical research.
Reactive oxygen species (ROS) are signaling molecules that are important in physiological processes, including host defense, aging, and cellular homeostasis. Increased ROS bioavailability and altered redox signaling (oxidative stress) have been implicated in the onset and/or progression of chronic diseases, including hypertension. Although oxidative stress may not be the only cause of hypertension, it amplifies blood pressure elevation in the presence of other pro-hypertensive factors, such as salt loading, activation of the renin-angiotensin-aldosterone system, and sympathetic hyperactivity, at least in experimental models. A major source for ROS in the cardiovascular-renal system is a family of nicotinamide adenine dinucleotide phosphate oxidases (Noxs), including the prototypic Nox2-based Nox, and Nox family members: Nox1, Nox4, and Nox5. Although extensive experimental data support a role for increased ROS levels and altered redox signaling in the pathogenesis of hypertension, the role in clinical hypertension is unclear, as a direct causative role of ROS in blood pressure elevation has yet to be demonstrated in humans. Nevertheless, what is becoming increasingly evident is that abnormal ROS regulation and aberrant signaling through redox-sensitive pathways are important in the pathophysiological processes which is associated with vascular injury and target-organ damage in hypertension. There is a paucity of clinical information related to the mechanisms of oxidative stress and blood pressure elevation, and a few assays accurately measure ROS directly in patients. Such further ROS research is needed in humans and in the development of adequately validated analytical methods to accurately assess oxidative stress in the clinic.


Induction of hormone-sensitive lipase/cholesteryl esterase gene expression by C/EBPα independently of the PKA pathway in the adrenocortical Y-1 cells.
The effect of C/EBPα on the expression of LIPE gene encoding hormone-sensitive lipase/cholesteryl esterase (HSL) was investigated in Y-1 CCL79 cells. It was found that transfection of these cells with the vector overexpressing C/EBPα increased both the level of LIPE transcript, measured by RT-qPCR, and the luminesce emitted by luciferase reporter gene fused to the -2150 fragment of LIPE promoter. Activation of adenylyl cyclase by forskolin resulted in 2.5-fold increase in the intensity of luminescence and over 3-fold increase in luminescence was observed when the cells were cotransfected with the vector overexpressing C/EBP. The incubation of C/EBP-cotransfected cells with forskolin caused over 6-fold increase in the intensity of luminescence, suggesting that the effects of C/EBPα and forskolin are additive. The analysis of sequence of the proximal LIPE promoter showed multiple binding sites for various transcription factors including C/EBPα site, which is located between nucleotides -46 bp and -59 bp. When the Y-1 cells were transfected with the recombinant vector containing -60 bp fragment of LIPE promoter fused to the luciferase reporter gene and were cotransfected with the vector overexpressing C/EBPα, the luminescence increases about 9-fold indicating that C/EBPα stimulates the expression of LIPE by reacting with its response element. The results indicate that C/EBPα stimulates the expression of LIPE independently of the PKA pathway by binding to a response element situated within the -60 bp fragment of LIPE promoter. This suggests that C/EBPα might be involved in the regulation of LIPE expression and thus cholesterol supply for steroid hormone synthesis.


Different prognostic effect of postoperative chemoradiation therapy on diploid and nondiploid high-risk rectal cancers.
DNA ploidy has been shown to play a role in the response to cytotoxic therapy in a variety of malignancies, including breast cancer and melanoma. However, the importance of DNA ploidy in rectal cancer is unknown. The aim of the present study was to determine whether ploidy status might be associated with response to postoperative chemoradiation in TNM Stages II to III rectal cancer. This retrospective study analyzed data from 229 patients with TNM Stages II to III rectal cancer who underwent resection between 1979 and 1984. The ploidy status and treatment modalities in relation to outcome were assessed. The recurrence-free ten-year survival rate was 52.2 percent for patients with diploidy and 50.5 percent for patients with nondiploidy (P = 0.99). The ten-year survival rates for patients with diploidy and patients with nondiploidy were 55 and 19 percent (P = 0.016) in the chemoradiation group, and 51 and 60 percent (P = 0.15) in the nonchemoradiation group, respectively. In the chemoradiation group, DNA nondiploidy was associated with an increased recurrence rate (83.3 vs. 50.0 percent; P = 0.001). The interaction between DNA nondiploidy and chemoradiation remained important in predicting outcome in the Cox regression model. Factors independently correlated with a worse outcome included Stage IIIb (relative risk, 2.9; 95 percent confidence interval, 1.7-5; P = 0.0001), perineural invasion (relative risk, 2.5; 95 percent confidence interval, 1.6-4, P = 0.0001), distal tumor (relative risk, 1.7; 95 percent confidence interval, 1.1-2.7, P = 0.014), and nondiploidy with chemoradiation (relative risk, 2.9; 95 percent confidence interval, 1.2-7.2, P = 0.0213). These findings suggest that DNA nondiploidy is inversely correlated with long-term outcome among patients with high-risk rectal cancer receiving chemoradiation.


Joint kinematic and kinetic responses to added mass on the lower extremities during running.
We analyzed the biomechanical response (joint angles, moments, and powers) to running with added leg mass. These data may help guide the design of wearable locomotor assistive devices (i.e., exoskeletons), which are becoming more prevalent. 15 participants (7 females, 8 males) completed treadmill running trials (3m•s-1) normally and with lead mass (300-1350 g) attached to the thigh, shank, or foot, bilaterally. We quantified the lower limb biomechanics combining motion capture and ground reaction force data using standard inverse dynamics analysis. Only moderate kinematic changes occurred in response to the distal added limb mass. Maximum hip flexion and maximum knee flexion angles during swing phase increased by approximately 9% and 6% respectively for each 1 kg added to each foot. However, adding even small masses made dramatic changes to the joint moments and powers, mostly during the swing phase. For example, adding 1 kg to each foot increased maximum joint moments by as much as 40% (knee extension in late swing) and maximum joint power by as much as 50% (hip generation in late swing). Leg joint kinematics were largely conserved in response to adding mass to the legs. Adding mass to the leg distally increased joint power mainly at the knee and hip joints during the swing phase, whereas adding mass proximally mainly affected the ankle joint mechanics during the stance phase. These changes have implications for shoe designs, people who run with added mass on their legs for sport/strength training and for the design of wearable devices.


The unitary modification rules for neural networks with excitatory and inhibitory synaptic plasticity.
The unitary Hebbian modification rules for homo-, hetero- and associative LTP and LTD of excitatory and inhibitory synaptic transmission in the neocortex and hippocampus is proposed. To provide the realization of Hebbian rule it is postulated that only synapses activated by the transmitter are modifiable. The necessary condition for the induction of heterosynaptic LTD is the convergence of homo- and heterosynaptic afferents on both the target cell and 'common' inhibitory interneuron; and modification of common inhibitory pathway efficacy. It is revealed by computational model of postsynaptic processes that in a stationary state post-tetanic synaptic efficacy does not depend on the initial efficacy but is completely defined by the amount of transmitter released during tetanization. Excitatory (inhibitory) synaptic efficacy monotonically increases (decreases) with the intracellular Ca2+ rise that is proportional to stimulation frequency enlargement. Hebbian rule, the coincidence of pre- and postsynaptic cell activity, is only necessary conditions for synaptic plasticity. Modification, such as simultaneous LTP of excitation and LTD of inhibition (LTD of excitation and LTP of inhibition) could be obtained only due to variations in pre- and/or postsynaptic activity and subsequent positive (negative) shift in the ratio between protein kinases and phosphatases in reference to prior ratio.


Wogonoside displays anti-inflammatory effects through modulating inflammatory mediator expression using RAW264.7 cells.
The root of Scutellaria baicalensis Georgi, also called Huangqin in China, is an herbal-based nutraceutical which is usually used in Chinese medicated diet (CMD). As an abundant ingredient in Huangqin, wogonoside is a flavonoid glycoside. The present work investigated the anti-inflammatory activities of wogonoside in lipopolysaccharides (LPS)-induced RAW264.7 cells. RAW264.7 cells were used. The inhibition of wogonoside against nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in LPS-induced RAW264.7 cells were measured. Additionally, the effects of wogonoside on mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX2), TNF-α and IL-6 were also investigated. Wogonoside not only dose-dependently decreased the production of inflammatory mediators including NO and PGE2 but also inhibited the release of pro-inflammatory cytokines including TNF-α and IL-6 in LPS-induced RAW264.7 cells. Furthermore, wogonoside possessed significantly in vitro inhibitory effects on the gene expression of iNOS, COX2, TNF-α and IL-6. These results suggest that wogonoside may be used as a functional food component for prevention and treatment of inflammation.


Anxiety disorders in intimate partners and the quality of their relationship.
The aim of this study was to explain whether anxiety disorders presenting in one or both partners of a relationship can influence the latter and to what extent. This study included 85 couples, where: 1) the male partner suffered from an anxiety disorder and female partner was free from this type of disorder (F((-))M((+)), n=20); 2) the female partner suffered from an anxiety disorder and the male partner was free from this type of disorder (F((+))M((-)); n=40); and 3) both partners were affected with anxiety disorders (F((+))M((+)), n=25). The quality of the relationship was assessed by both partners using three different scales: 1) Dyadic Adjustment Scale (DAS), 2) Family Attitude Scale (FAS), and 3) Marriage Success Scale (SPM). In case of the SPM scale, women from F((-))M((+)) group evaluated their marriages significantly compared to other groups. In case of males, the self-evaluated quality of marriage was the lowest in the case of individuals from F((+))M((+)) group. In case of the DAS scale, women and men being free from anxiety disorders assessed the quality of their relationships significantly higher than other participants. The analyzed groups did not differ significantly in terms of mean values scored in the FAS scale. The lack of a multifactorial analysis taking into account the effects of a variety of anxiety disorders. The presence of anxiety disorders in at least one partner negatively affects the quality of partner relationship. The couples where the female partners are affected are particularly fragile.


The effectiveness of television advertising campaigns on generating calls to a national Quitline by Māori.
To examine the effectiveness of four mass media campaigns on calls to a national Quitline by Māori (the indigenous people of New Zealand). Monthly Quitline call data and calls within one hour of a television commercial (TVC) being shown were analysed for the 2002-2003 period. Data on target audience rating points (TARPs) and expenditure on TVCs were also used (n = 2319 TVC placements). Māori were found to register with the Quitline at higher rates during the most intense six campaign months (15% more registrations compared to less intense months). The most effective campaign generated 115 calls per 100 TARPs by Māori callers within one hour of TVC airing (the "Every cigarette" campaign). A more Māori orientated campaign with both health and cultural themes generated 91 calls per 100 TARPs from Māori callers. For these two campaigns combined, the advertising cost per new registration with the Quitline by a Māori caller was NZD 30-48. Two second hand smoke campaigns that did not show the Quitline number were much less effective at 25 and 45 calls per 100 TARPs. These television advertising campaigns were effective and cost effective in generating calls to a national Quitline by Māori. Health authorities should continue to explore the use of both "threat appeal" style media campaigns and culturally appropriate campaigns to support Quitline use by indigenous peoples.


Cryptogenic ischemic stroke and silent atrial fibrillation: What is the relationship?
Atrial fibrillation (AF) is responsible for up to one-third of ischemic strokes and associated with silent cerebral infarctions and transient ischemic attacks. Any method that predicts the stroke or unmasks the silent PAF would contribute to the treatment of ischemic stroke. Intraatrial conduction time (ICT) has been shown to be associated with intermittent AF. In this study, we evaluated the value of ICT detected by transthoracic echocardiography in normal population and in patients with cryptogenic stroke (CS) as a risk factor for stroke. The patients with CS and with normal left ventricular function without valvular disease are included in group 1. Patients with atypical symptoms admitted to cardiology clinics without any risk factor for cardiac disease and found to be normal constituted group 2. Age, gender, weight, height, echocardiographic parameters and ICT were compared between groups. 63 and 64 subjects were included in group 1 and 2, respectively. Two groups were similar according to age and gender. Among the parameters studied, left atrial diameter and height of the patients were significantly higher in group 1 (40 ± 2 vs 37 ± 4 mm, p < 0.001 and 167 ± 9 vs 163 ± 9 cm p = 0.027, respectively). ICT was significantly higher in group 1 (131 ± 15 vs 118 ± 13 ms, respectively, p < 0.000). According to ROC analysis, a cut point of 124 ms for ICT with a sensitivity of 74 % and specificity of 73 % in patients with CS (p < 0.001). This study show us, the measurements the ICT determined by means of echocardiography is longer in patients with CS. This simple and noninvasive technique can be applied widely and lead the clinicians to adopt the use of diagnostic and the treatment procedures.


Rapid sequence spinal anaesthesia: a technique reborn during the COVID-19 pandemic.
With the wish to reduce aerosol generation and the shorter time to anaesthetic readiness, this article discusses why rapid sequence spinal anaesthesia could be used in preference to general anaesthesia, for the benefit of both patients and staff during the COVID-19 pandemic.


Attention deficit disorder: current perspectives.
This review focuses on selected issues in the rapidly proliferating scientific literature on attention deficit disorder (ADD). It encompasses a brief overview of ADD, including a review of the historical trends, causation, and a description of the clinical characteristics. Critical issues fundamental to understanding of ADD are addressed next. Evidence is presented to suggest that there are several groups of children with ADD who are currently under-identified and therefore, underserved (girls with ADD; ADD without hyperactivity). The concept is introduced of uncomplicated ADD and ADD-Plus (ADD-P), a term used to designate ADD associated with other complicating features such as conduct disorder. Specific methodologic issues and their relationship to the under-identification of these groups of children follows. This discussion encompasses the reasons for diagnostic imprecision and inconsistency, emphasizing the problem of selective referral patterns and how it results in an inaccurate portrait of ADD. We then present new approaches to the definition and diagnosis of ADD based on empiric studies designed to circumvent some of these problems. We conclude with a summary of the implications of these findings, and recommendations for public policy in ADD, particularly the need to recognize that ADD may occur even in the most intellectually gifted individuals and even in students in select colleges. Often these children with the highest potential are penalized most, not because of conceptual limitations or because they do not understand, but because educators often fail to recognize the symptom complex. Many of these children are succeeding through intelligence and great effort, but many more could succeed with proper identification.


In vitro Inhibition Profiles and Molecular Docking Analysis of Benzohydrazide Derivatives on Red Blood Cell Carbonic Anhydrases Isozymes.
Carbonic anhydrases (CAs, EC 18.104.22.168) are metalloenzymes that contain zinc ions on the active side and convert carbon dioxide to bicarbonate in metabolism. Human CA-I and CA-II, which are the most abundant CA isozymes in erythrocytes, have been therapeutic targets in the treatment of glaucoma, hypertension, ulcer, osteoporosis, and, neurological disorders. Benzohydrazides are biologically active compounds, and their various pharmacological effects have been reported. In light of this, the objective of this study was to investigate the in vitro effects of benzohydrazide derivatives on the activities of hCA-I and hCA-II, determine the compounds as selective inhibitors for these isoenzymes, and estimate the inhibition mechanism through molecular docking studies. In this work, we synthesized the 10 different derivatives of benzohydrazide containing various functional group of different positions. As a result, all benzohydrazide derivatives inhibited both isozymes in vitro and 2-amino 3- nitro benzohydrazide (10) was found to be the most efficient inhibitor of both hCA isozymes with the IC50 values of 0.030 and 0.047 μM, respectively. In the molecular docking studies, 3-amino 2- methyl benzohydrazide (3) had the lowest estimated free binding energies against hCA isozymes as -6.43 and -6.13 kcal/mol. In this study, hCA-I & II isozymes were isolate from human erythrocytes. CA isozymes are one of these target enzymes. WBC hope that the benzohydrazide derivatives, can guide remedies targeting carbonic anhydrase.


Argon laser photocoagulation of subretinal neovascular membrane associated with osteoma of the choroid.
A 19-year-old white woman with osteoma of the choroid developed a subretinal neovascular membrane with hemorrhage. This was treated with Argon laser photocoagulation and she has shown no evidence of recurrence 13 months after treatment.


Affinity chromatography with 25-hydroxycholecalciferol ester in the isolation of the binding protein for vitamin D and its metabolites from human serum.
The 3 beta-hemisuccinate ester of 25-hydroxycholecalciferol was prepared by incubating the sterol with succinic acid anhydride in the presence of 4-dimethylaminopyridine at 4 degrees. The ester was isolated by silica gel column chromatography, and its hydrolysis in ethanolic sodium hydroxide yielded 25-hydroxycholecalciferol. The ester was covalently linked to aminoagarose in the presence of isobutylchloroformate, yielding 16 to 60 micrograms of sterol per packed ml of gel. Normal human serum was applied to the 3 beta-hemisuccinate-25-OH-D3 aminoagarose gel and elutions with buffer of increasing molarity were carried out. Total protein and DBP content of the 6M guanidine elution fractions revealed a 12 to 134-fold purification of human serum DBP by this technique. Best purifications were achieved by incubating serum with the gel at pH 8.3 and rinsing the gel with 0.3 M KCl prior to its elution with the guanidine. Our results indicate that affinity chromatography with this ligand, or possibly other vitamin D sterol esters, is a practical and useful technique in the analysis and preparative isolation of vitamin D sterol-binding proteins.


Determinants of the effect of estrogen on the progression of subclinical atherosclerosis: Estrogen in the Prevention of Atherosclerosis Trial.
To determine the extent to which the estrogen-induced changes in lipids and markers of carbohydrate metabolism explain the beneficial effect of estrogen therapy on the progression of carotid artery intima-media thickness (IMT) in postmenopausal women. A randomized, double-blind, placebo-controlled, single-center trial enrolling 222 postmenopausal women 45 years and older without cardiovascular disease and with low-density lipoprotein (LDL) cholesterol levels of 3.37 mmol/L or greater (> or = 130 mg/dL). Intervention was unopposed micronized 17beta-estradiol versus placebo. Measurements were made using high-resolution B-mode ultrasonography to measure carotid artery IMT at baseline and every 6 months on-trial. Progression of carotid IMT was inversely related to on-trial high-density lipoprotein (HDL) cholesterol (P = 0.04) and was directly related to on-trial LDL-cholesterol (P = 0.005). Compared with placebo, women randomized to estradiol showed a higher mean on-trial HDL-cholesterol level and a lower mean on-trial LDL-cholesterol level. In contrast, fasting glucose, insulin, and hemoglobin A1C were lowered and insulin sensitivity increased with estradiol therapy, but the changes were not related to carotid IMT progression. On-trial HDL-cholesterol and LDL-cholesterol were significant independent determinants of carotid IMT progression, jointly explaining 30% of the treatment effect of unopposed estrogen on the progression of carotid IMT. Unopposed 17beta-estradiol reduced carotid IMT progression in postmenopausal women in part by increasing HDL-cholesterol and decreasing LDL-cholesterol. Although women randomized to estradiol showed improvement in all the markers of carbohydrate metabolism, these factors did not play a significant role in carotid IMT progression.


Biochemical analysis of selenoprotein expression in brain cell lines and in distinct brain regions.
Selenium is present in various biologically important selenoproteins. The preferential incorporation of selenium into the brain indicates its significance for this organ, but so far knowledge concerning the cerebral selenoproteome is scarce. We therefore investigated the expression of selenoproteins in various regions of the rat brain, various subcellular fractions and several brain cell lines by (75)Se-labelling, gel electrophoretic separation and autoradiography, with the (75)Se tracer as the selenoprotein marker. Quantitative evaluation of the labelled proteins in selenium-deficient rats revealed information regarding preferentially supplied selenoproteins and their distribution; 21 selenoproteins could be distinguished, among them a novel or modified 15-kDa selenoprotein enriched in the cerebellum cytosol. The selenoproteins differed in the degree of their expression among the brain regions and within a region among the subcellular fractions. Some cell-type-specific selenium-containing proteins were found in the cell lines. Differences in the distribution patterns between mono-cultured and co-cultured endothelial cells and astrocytes showed that mediators produced by other cells could affect the selenoprotein expression of a specific cell-type. This effect might play a role in the uptake and distribution of selenium in the brain but could also be of significance in the selenium metabolism of other tissues.


Constructions of chronic pain in doctor-patient relationships: bridging the communication chasm.
This study examined interactions between doctors and their chronic pain patients in the context of investigations for medically unexplained pain. Doctor-patient interactions were explored through the analysis of the accounts of the communication process in the chronic pain consultation of 20 chronic pain patients with their pain specialists and the accounts of 22 pain specialists with their chronic pain patients. An implicit dialogue between doctors and their patients was identified that appeared to undermine the quality of their interactions, challenged each other's credibility and caused distress to both parties. The implicit dialogue of the chronic pain patient was based on the biogenic theory while the implicit dialogue of doctors was underpinned by psychogenic theory. Potentially healing interactions between doctors and their patients that do not rely on the biogenic model of the visible body or the psychogenic model of invisible pain are needed to assist the communication between chronic pain patients and their doctors. A systemic theoretical analysis of this process is offered.


The impact of hysterectomy on oncological outcomes in postmenopausal patients with borderline ovarian tumors: A multicenter retrospective study.
Data about the oncological outcomes in women with borderline ovarian tumor (BOT) undergoing uterine-sparing surgery without ovarian preservation are poor. We aimed to assess the oncological outcomes in women with BOT undergoing uterine-sparing surgery without ovarian preservation. A multi-center observational retrospective cohort study was performed including all consecutive postmenopausal patients who underwent surgical treatment for BOT at three tertiary level referral centers for gynecologic oncology from January 2005 to December 2016. Patients were divided into two groups for comparisons: patients undergoing hysterectomy (hysterectomy group) and patients undergoing uterine-sparing surgery (no hysterectomy group). Study outcomes were disease-free survival (DFS), overall survival (OS), disease-specific survival (DSS) and surgical complications rate. Ninety-eight patients were included: 44 in the hysterectomy group and 54 in the no hysterectomy group. The 5- and 10-year DFS rates were 97.7% (95% CI: 84.9-99.7) and 92.3% (95% CI: 69.7-98.2), in the hysterectomy group, and 86.8% (95% CI: 74.3-93.5) and 86.8% (95% CI: 74.3-93.5), in the no hysterectomy group, respectively, without significant differences (p=0.16). Hazard ratio for DFS was 0.26 (95% CI: 0.06-1.68) for the hysterectomy group. The 5- and 10-year OS rates were 100.0% (95% CI: -) and 100.0% (95% CI: -), in the hysterectomy group, and 98.2% (95% CI: 87.6-99.7) and 94.4% (95% CI: 77.7-98.7), in the no hysterectomy group, respectively, without significant differences (p=0.23). No significant difference in complication rate was reported among the groups (p=0.48). As hysterectomy appears to not impact survival outcomes of women with BOT, it might be avoided in the surgical staging.


Effects of validamycin A on the morphology, growth and sporulation of Rhizoctonia cerealis, Fusarium culmorum and other fungi.
All Basidiomycotina screened were sensitive to validamycin A, whereas most Ascomycotina and all Mucorales and Oomycetes were insensitive. Studies with Rhizoctonia cerealis and Fusarium culmorum showed that, in semi-solid culture, the antibiotic caused a decrease in colony radial growth rate and that this was associated with a decrease in mean hyphal extension rate and an increase in hyphal branching. However, the antibiotic did not alter the morphology of R. cerealis grown in liquid culture (shaken or stationary). Validamycin A caused a reduction in the number and viability of conidia produced by F. culmorum.


Current trends in the management of radical retropubic prostatectomy: is short-stay RRP feasible in the United Kingdom?
Our aim was to review UK practice in the management of radical retropubic prostatectomy and identify opportunities to reduce LOS to American levels. A survey was conducted of BAUS members regarding LOS and postoperative management. Out of 551 surveys 126 were returned. Mean LOS in the UK is 5.2 days. Opiate analgesia, PCA and postoperative epidural may delay discharge. Diet and mobilization are commenced at 1.7 and 2.1 days, respectively. Care pathways can safely reduce LOS to 2 days. Protocols to reduce LOS in the UK should be assessed and their impact on cost and quality-of-life evaluated.


The role of aldosterone antagonists in the management of resistant hypertension.
Resistant hypertension is an increasingly common problem faced by primary care physicians and specialists and will undoubtedly become even more common as the adult population ages and gains weight. In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), at least 8% of subjects were resistant to treatment based on the need for three or more antihypertensive agents. Characteristics of patients with resistant hypertension include being older, black, obese, and diabetic, and having chronic kidney disease as well as untreated sleep apnea. Hyperaldosteronism is common in patients with resistant hypertension, with a prevalence of approximately 20%. This, however, is likely an underestimation of the role aldosterone excess plays in causing drug resistance. In subjects with resistant hypertension, suppressed renin levels are common, exceeding 75% in our studies, suggesting aldosterone excess effects beyond cases of true primary hyperaldosteronism. Recent studies indicate that aldosterone antagonists provide significant blood pressure reduction when added to antihypertensive regimens of patients with resistant hypertension. Interestingly, the blood pressure reduction with use of spironolactone is not limited to patients with hyperaldosteronism, consistent with the concept of aldosterone excess as a continuum from low-renin hypertension with normal aldosterone levels to true primary hyperaldosteronism.


[Mitochondrial DNA variation in diploid and triploid forms of silver crucian carp Carassius auratus gibelio].
Variation of two mtDNA fragments amplified in polymerase chain reaction was compared by the RFLP method in a population of the sympatric bisexual (diploid) and gynogenetic (triploid) forms of silver crucian carp. The mtDNA haplotypes of all individuals differed in at least 2.5% of nucleotide substitutions and fall into two phylogroups. All gynogenetic individuals have haplotypes of a single phylogroup, whereas haplotypes of diploid fish belonged to both mtDNA phylogroups. This testifies to a possibility of transformation of gynogenetic individuals into a bisexual form, whereas the reverse process is either extremely rare or impossible.


Induction of protective immunity to Listeria monocytogenes by immunization with plasmid DNA expressing a helper T-cell epitope that replaces the class II-associated invariant chain peptide of the invariant chain.
Listeria epitope-specific helper T (Th) cells were able to be primed and induced in vivo by immunization with a plasmid carrying an invariant chain (Ii) gene whose class II-associated invariant chain peptide (CLIP) region was replaced by a Listeria Th epitope. Immunization of C3H/He mice with an Ii-LLO 215-226 plasmid induced specific interferon-gamma- and interleukin 2-producing Th cells and conferred significant protective immunity against listerial infection.


[The role of thrombocyte aggregation function in the mechanism of the antimetastatic action of an extract of Baikal skullcap].
The advancement of Pliss' lymphosarcoma in rats was shown to be associated with disorders of platelet-mediated hemostasis presenting with either lowered or increased aggregation activity of platelets. In the latter case, a direct correlation was observed between functional activity of thrombocytes, on the one hand, and degree of tumor advancement and its metastatic activity, on the other. Extract of Scutellaria baicalensis Georgi was shown to produce a normalizing effect on platelet-mediated hemostasis whatever the pattern of alteration which points to the adaptogenic activity of the drug. This activity is thought to be responsible for the drug's antitumor and, particularly, metastasis-preventing effect.


Porokeratosis of Mibelli. A report of two unusual cases.
2 cases are reported with unusual manifestations of porokeratosis of Mibelli. In 1 case multiple atrophic facial lesions resembled plaques of chronic discoid lupus erythematosus. The second case exhibited extensive cutaneous involvement in the form of hyperkeratotic lesions in linear configuration.