Two distinct Notch signals, Delta-like 4/Notch1 and Jagged-1/Notch2, antagonistically regulate chemical hepatocarcinogenesis in mice.
Notch signaling is one of the most common drivers of carcinogenesis in many types of cancers, including hepatocellular carcinoma (HCC); however, it occasionally suppresses tumor progression. Moreover, it is virtually unknown how different sets of Notch ligands and receptors regulate the HCC development. In this study, we demonstrate that the expression of the Notch ligands, Delta-like 4 (Dll4) and Jagged-1 (Jag1), is upregulated during diethylnitrosamine-induced hepatocarcinogenesis. Dll4 is detected in the preneoplastic hepatocytes and HCC cells, but not in the normal hepatocytes, while Jag1 is expressed in the desmin-positive mesenchymal cells. Hepatocyte-specific Dll4 knockout abolishes the Notch1 signaling and suppresses the tumor progression. In contrast, Jag1 deletion induces the ectopic expression of Dll4 in hepatocytes along with the loss of Notch2 signaling, leading to the tumor progression. These results indicate that the two distinct Notch signals, Dll4/Notch1 and Jag1/Notch2, are antagonistic to each other, exerting opposite effects on HCC progression.


A review of lobular, portal, and periportal hepatitis. Interpretation of biopsy specimens without clinical data.
This representation, in which a recently adopted terminology is used, represents a compilation of clinical diagnoses that must be considered whenever a morphologic diagnosis of lobular, portal, or periportal hepatitis has been made. Also described are the morphologic findings that may enable the pathologist to list, without knowledge of clinical data, the suspected clinical conditions in an order of likelihood.


Dopaminergic function in relation to genes associated with risk for schizophrenia: translational mutant mouse models.
Mutant mice play an increasingly important role in understanding disease processes at multiple levels. In particular, they illuminate the impact of risk genes for disease on such processes. This article reviews recent advances in the application of mutant mice to study the intricacies of dopaminergic (DAergic) function in relation to the putative pathophysiology of psychotic illness, particularly schizophrenia, and antipsychotic drug action. It considers models for understanding the role(s) of risk genes, with a particular focus on DTNBP1 and NRG1, their interactions with environmental factors, and with each other (epistasis). In overview, it considers new schemas for understanding psychotic illness that integrate DAergic pathophysiology with developmental, social, and cognitive processes, and how mutant mouse models can reflect and inform on such schemas.


Preliminary study on calcium aluminosilicate glass as a potential host matrix for radioactive 90Sr--an approach based on natural analogue study.
Given the environmental-, safety- and security risks associated with sealed radioactive sources it is important to identify suitable host matrices for (90)Sr that is used for various peaceful applications. As SrO promotes phase separation within borosilicate melt, aluminosilicate bulk compositions belonging to anorthite-wollastonite-gehlenite stability field are studied in this work. Tests for their homogeneity, microstructural characteristics and resistance to phase separation narrowed the choice down to the composition CAS11 (CaO=35 wt%, Al(2)O(3)=20 wt%, SiO(2)=45 wt%). We find that up to 30 wt% SrO can be loaded in this glass without phase separation (into Ca, Sr-rich and Sr-poor, Si-rich domains). Leaching behaviour of the glasses differs depending on the content and distribution of Sr. In general, the elemental leach rates determined from conventional PCT experimental procedure yield values better than 10(-7)gcm(-2)day(-1) for both CAS11 base glass as well as SrO doped glass. It was noted that leach rates calculated on the basis of Ca(2+) and Sr(2+) were of the same order and bit higher compared to those calculated on the basis of Si(4+) and Al(3+). During accelerated leaching tests, zeolite and zeolite+epidote were found to have developed on CAS11 base glass and SrO doped glasses respectively. The Sr bulk diffusion coefficients is found to vary from ∼ 10(-15) to 10(-13)cm(2)/s at temperature intervals as high as 725-850°C. Based on the experimental observations, it is suggested that CAS11 glass can be used as host matrix of (90)Sr for various applications of radioactive Sr-pencils.


Effects of biofilm on metal adsorption behavior and microbial community of microplastics.
In this study, the adsorption behavior of Cu(II) and Pb(II) on the biofilm-developed polystyrene (PS) microplastics (MPs) was compared with the virgin PS (V-PS) and UV-aged PS (UV-PS). The results demonstrated that the biofilm could enhance the adsorption abilities onto MPs more than UV radiation. The intra-particle diffusion model suggested that the adsorption on V-PS was dominated by intra-particle diffusion, while the adsorption rate was controlled by the binding diffusion on UV-PS and biofilm-developed PS (Bio-PS). Compared with the V-PS and UV-PS, the Bio-PS showed the largest adsorption capacity based on the Freundlich isotherm model, which indicated that the adsorption of heavy metals onto Bio-PS was multilayer and heterogeneous. The adsorption mechanism of Bio-PS contained physical adsorption, chemisorption, and biosorption. These Bio-PS adsorption types participated in both oxygen and nitrogen groups. Based on the 16S rRNA analysis, the diversity of the microbial community with biofilm changed to a certain extent after the adsorption of heavy metals. Furthermore, the stress of lead (Pb) adsorption had a higher impact on the microbial community distribution and the PS biofilm. This study illustrated how the formation of biofilms can highly affect the adsorption behavior of MPs as well as the microbial community of MPs.


FlowCT for the analysis of large immunophenotypic data sets and biomarker discovery in cancer immunology.
Large-scale immune monitoring is becoming routinely used in clinical trials to identify determinants of treatment responsiveness, particularly to immunotherapies. Flow cytometry remains one of the most versatile and high throughput approaches for single-cell analysis; however, manual interpretation of multidimensional data poses a challenge when attempting to capture full cellular diversity and provide reproducible results. We present FlowCT, a semi-automated workspace empowered to analyze large data sets. It includes pre-processing, normalization, multiple dimensionality reduction techniques, automated clustering, and predictive modeling tools. As a proof of concept, we used FlowCT to compare the T-cell compartment in bone marrow (BM) with peripheral blood (PB) from patients with smoldering multiple myeloma (SMM), identify minimally invasive immune biomarkers of progression from smoldering to active MM, define prognostic T-cell subsets in the BM of patients with active MM after treatment intensification, and assess the longitudinal effect of maintenance therapy in BM T cells. A total of 354 samples were analyzed and immune signatures predictive of malignant transformation were identified in 150 patients with SMM (hazard ratio [HR], 1.7; P < .001). We also determined progression-free survival (HR, 4.09; P < .0001) and overall survival (HR, 3.12; P = .047) in 100 patients with active MM. New data also emerged about stem cell memory T cells, the concordance between immune profiles in BM and PB, and the immunomodulatory effect of maintenance therapy. FlowCT is a new open-source computational approach that can be readily implemented by research laboratories to perform quality control, analyze high-dimensional data, unveil cellular diversity, and objectively identify biomarkers in large immune monitoring studies. These trials were registered at www.clinicaltrials.gov as #NCT01916252 and #NCT02406144.


Tocochromanols and carotenoids in sorghum (Sorghum bicolor L.): diversity and stability to the heat treatment.
The content and stability (retention) to dry heat in a conventional oven (DHCO) and extrusion of tocochromanols and carotenoids in sorghum genotypes were evaluated. One hundred sorghum genotypes showed high variability in tocochromanol content (280.7-2962.4 μg/100g in wet basis) and 23% of the genotypes were classified as source of vitamin E. The total carotenoid varied from 2.12 to 85.46 μg/100g in one hundred sorghum genotypes. According to the genetic variability for carotenoids and tocochromanols, the 100 genotypes were grouped into 7 groups. The retention of the total tocochromanols and α-tocopherol equivalent decreased after extrusion (69.1-84.8% and 52.4-85.0%, respectively) but increased after DHCO (106.8-114.7% and 109.9-115.8%, respectively). Sorghum carotenoids were sensitive to extrusion (30.7-37.1%) and DHCO (58.6-79.2%). In conclusion, the tocochromanols profile in sorghum varied widely and the genotypes presented high genetic variability for carotenoids and tocochromanols. Sorghum was a source of tocochromanols, which increased after DHCO and decreased after extrusion. The carotenoid content in sorghum decreased after DHCO and extrusion.


Flow cytometrical considerations. The results of three different ways of nuclear preparation and two ways of calculating upon DNA index, number of populations and S-phase rate in endometrial tissue.
Histopathologically normal endometrial tissues were used to compare the preparation methods of Tribukait, Thornthwaite and Vindelöv. Three hundred and forty-one preparations were analyzed giving as a result significant differences regarding the DNA-indices, number of DNA-populations and percentage of cells in S-phase fraction. We also compared a manual way of calculation to a semi-automatic method (RFIT). No difference was found between the manual way and RFIT provided that the same internal standard was used. However, the two different internal standards gave different results within the same method of preparation.


The CXCL12-3'A allele is associated with a higher mobilization yield of CD34 progenitors to the peripheral blood of healthy donors for allogeneic transplantation.
The interaction between CXCL12 and its receptor CXCR4 plays a crucial role in the homing and mobilization of haematopoietic progenitors. We investigated the putative association between a CXCL12 gene polymorphism, the G --> A transition at position 801 in the 3'-untranslated region (3'UTR), and the yield of CD34(+) progenitors in 65 healthy allogeneic transplant donors who received G-CSF. Importantly, in this setting, the analysis was not biased by background disease or chemotherapy. The 3'UTR CXCL12 G801A polymorphism was detected using a PCR-RFLP technique with the MspI restriction enzyme and the frequency of CD34(+) progenitors was assessed by flow cytometry. The frequency as well as the number of CD34(+) progenitor cells in the first leukapheresis product was significantly higher from donors with the CXCL12-3'A allele compared to GG homozygotes (P<0.05 in both cases), especially for subjects with the CXCL12-3'AA homozygous genotype (P<0.01 in both cases). Moreover, more leukaphereses were needed to obtain the required number of CD34(+) progenitors for transplantation from CXCL12-3'GG homozygous donors compared to the CXCL12-3'A carriers (P=0.003). In conclusion, the CXCL12-3'A allele was associated with a higher yield of CD34(+) cells from healthy donors of PBPC for allogeneic haematopoietic SCT.


Laparoscopic proximal gastrectomy with right-sided overlap and single-flap valvuloplasty (ROSF): a case-series study.
There is no standard reconstruction method following proximal gastrectomy, of which gastroesophageal reflux and anastomotic complications are of great concern. Though several techniques have been devised to overcome these postoperative complications, such as double tract reconstruction, double-flap technique and side overlap fundoplication by Yamashita, none of them is considered a perfect solution. Herein, we designed a novel method of esophagogastrostomy after laparoscopic proximal gastrectomy (LPG), named right-sided overlap and single-flap valvuloplasty (ROSF). Between March 2021 and December 2021, 20 consecutive patients underwent LPG-ROSF at Department of Gastrointestinal Surgery, Second Affiliated Hospital of Soochow University. Surgical outcomes and postoperative complications were recorded. All patients were followed-up until December 2022. Endoscopy and assessment of gastrointestinal symptoms were performed 1 year after surgery. Nutrition-related parameters including total body weight, hemoglobin, lymphocyte count, serum total protein, serum albumin and serum prealbumin were evaluated 1 year after surgery and compared with those before surgery. The mean surgery time and anastomosis time was 285.3 ± 71.3 and 61.3 ± 11.2 min respectively. None of the patients had gastrointestinal early postoperative complications. Symptomatic reflux was observed in one patient (5%) while reflux esophagitis (Los Angeles Grade A) was observed in another patient (5%). Four patients (20%) had mild dysphagia (Visick score = II) but none of them had anastomotic stenosis. There were no significant changes in nutritional status postoperatively. ROSF can be safely performed after LPG and has satisfactory outcomes in preventing reflux and stenosis, and maintaining nutritional status. This technique requires further validation.


Isothermal and temperature-cycling retrogradation of high-amylose corn starch: Impact of sonication on its structural and retrogradation properties.
In this study, the effects of sonication and temperature-cycled storage on the structural properties and resistant starch content of high-amylose corn starch were investigated. Sonication induced a partial depolymerization of the molecular structures of amylopectin and amylose. Sonication treatment induced the appropriate structural changes for retrogradation. Although the relative crystallinity of sonicated starch was lower than that of non-sonicated starch, sonicated starch after retrogradation showed much higher relative crystallinity than non-sonicated starch. Regardless of sonication treatment, temperature-cycled storage resulted in a higher degree of retrogradation than isothermal storage, but the rate of retrogradation was greater in sonicated starch than in non-sonicated starch, as supported by retrogradation enthalpy, the Avrami constant, and relative crystallinity. The highly developed crystalline structure in sonicated starches due to retrogradation was reflected by the large amount of resistant starch.


Aging, but not tau pathology, impacts olfactory performances and somatostatin systems in THY-Tau22 mice.
Somatostatin (SOM) cortical levels decline in Alzheimer's disease (AD) in correlation with cognitive impairment severity, the latter being closely related to the presence of neurofibrillary tangles. Impaired olfaction is another hallmark of AD tightly related to tau pathology in the olfactory pathways. Recent studies showed that SOM modulates olfactory processing, suggesting that alterations in SOM levels participate to olfactory deficits in AD. Herein, we first observed that human olfactory peduncle and cortex are enriched in SOM cells and fibers, in aged postmortem brains. Then, the possible link between SOM alterations and olfactory deficits was evaluated by exploring the impact of age and tau hyperphosphorylation on olfactory SOM networks and behavioral performances in THY-Tau22 mice, a tauopathy transgenic model. Distinct molecular repertoires of SOM peptide and receptors were associated to sensory or cortical olfactory processing structures. Aging mainly affected SOM neurotransmission in piriform and entorhinal cortex in wild-type mice, although olfactory performances decreased. However, no further olfactory impairment was evidenced in THY-Tau22 mice until 12 months although tau pathology early affected olfactory cortical structures. Thus, tau hyperphosphorylation per se has a limited impact on olfactory performances in THY-Tau22 mice.


Curcumin induces DNA damage and caffeine-insensitive cell cycle arrest in colorectal carcinoma HCT116 cells.
Curcumin (CUR), a polyphenol derived from the plant Curcuma longa, displays potential anti-cancer activity. One of the mechanisms stems from its ability to elicit cell cycle arrest followed by suppression of cell proliferation. Herein, we reported that CUR significantly induced DNA damage and mediated S and G2/M phase arrest in colorectal carcinoma HCT116 cells. Unlike etoposide, a classical topoisomerase II inhibitor, CUR-triggered G2/M phase arrest was hardly reversed by caffeine (CAFF) which is an inhibitor of activated ataxia-telangiectasia-mutated (ATM)/ATM- and Rad3-related (ATR), indicating that ATM and ATR signaling pathways may be not involved in CUR-mediated S and G2/M phase arrest in HCT116 cells. Furthermore, we demonstrated that CUR caused mitosis arrest in HCT116 cells by using mitotic protein monoclonal antibody-2 as a mitosis marker and the surface plasmon resonance assay. The findings provide new mechanisms of cell proliferation inhibition triggered by CUR in HCT116 cells.


Effect of revascularisation and apexification procedures on biomechanical behaviour of immature maxillary central incisor teeth: a three-dimensional finite element analysis study.
This study aimed to assess the effects of revascularisation and apexification procedures on biomechanical behaviour of immature teeth using 3-dimensional finite element analysis (3D FEA). Five 3D FEA permanent maxillary incisor models were developed from CBCT scans and available literature data: Model MT: Mature tooth, Model IT: Immature tooth (Cvek's stage 3), Model AT: Apexified tooth-mineral trioxide aggregate (MTA) apexification, Model RTB: Revascularised tooth with blood, and Model RTS: Revascularised tooth with supplementary scaffold. Using FEA, a masticatory load of 240N at 120° was simulated, and the Von Mises and maximum principal stresses within the models were evaluated. Failure index (FI) and weakening% were also calculated for each model. On dentinal stress analysis, model MT (96.16MPa) and IT (158.38MPa) had lowest and highest stress values, respectively. Among the experimental groups, model RTS (131.12MPa) had lower stresses than AT (136.33MPa) and RTB (133.7MPa), with no significant difference among the three. Peak dentinal stresses in all the models were observed in the cervical third of the root and near the apical opening in model IT. The extent of high dentinal stress area in model RTB and RTS was lesser than that of AT. The FI and weakening% values were highest for model AT followed by RTB and RTS, among the experimental groups. However, all these treatments strengthened an immature tooth by more than 20%. AT, RTB, and RTS treatments lowered the stress values and risk of fracture in immature teeth with no significant difference among the three groups. Stress distribution evaluation following revascularisation/apexification was essential, with potential to influence clinical decision-making. MTA apexification and revascularisation with blood clot/supplementary scaffold lowered the stresses in immature teeth, with no significant difference among the three.


Evaluation of the SARS-CoV-2 Inactivation Efficacy Associated With Buffers From Three Kits Used on High-Throughput RNA Extraction Platforms.
Rapid and demonstrable inactivation of SARS-CoV-2 is crucial to ensure operator safety during high-throughput testing of clinical samples. The inactivation efficacy of SARS-CoV-2 was evaluated using commercially available lysis buffers from three viral RNA extraction kits used on two high-throughput (96-well) RNA extraction platforms (Qiagen QIAcube HT and the Thermo Fisher KingFisher Flex) in combination with thermal treatment. Buffer volumes and sample ratios were chosen for their optimised suitability for RNA extraction rather than inactivation efficacy and tested against a representative sample type: SARS-CoV-2 spiked into viral transport medium (VTM). A lysis buffer mix from the MagMAX Pathogen RNA/DNA kit (Thermo Fisher), used on the KingFisher Flex, which included guanidinium isothiocyanate (GITC), a detergent, and isopropanol, demonstrated a minimum inactivation efficacy of 1 × 105 tissue culture infectious dose (TCID)50/ml. Alternative lysis buffer mixes from the MagMAX Viral/Pathogen Nucleic Acid kit (Thermo Fisher) also used on the KingFisher Flex and from the QIAamp 96 Virus QIAcube HT Kit (Qiagen) used on the QIAcube HT (both of which contained GITC and a detergent) reduced titres by 1 × 104 TCID50/ml but did not completely inactivate the virus. Heat treatment alone (15 min, 68°C) did not completely inactivate the virus, demonstrating a reduction of 1 × 103 TCID50/ml. When inactivation methods included both heat treatment and addition of lysis buffer, all methods were shown to completely inactivate SARS-CoV-2 inactivation against the viral titres tested. Results are discussed in the context of the operation of a high-throughput diagnostic laboratory.


Total knee replacement under tourniquet control: A prospective study of the peripheral arterial vasculature using colour-assisted duplex ultrasonography.
A tourniquet may potentiate rare and devastating arterial complications after total knee replacement (TKR) in patients with peripheral vascular disease (PVD). Most prior studies that evaluated peripheral arterial blood flow primarily used the ankle-brachial index (ABI). We assessed the prevalence and risk factors for PVD in a cohort undergoing TKR. Clinical and radiological evaluations, including duplex ultrasonography, were performed one week prior to, and six weeks post-TKR performed under tourniquet control. Forty patients were analysed (20 male, 20 female; mean age 67 yrs, range: 53-80 yrs). Hypertension (50%) and hypercholesterolaemia (50%) were the most common co-morbidities. Distal pulses were present in all patients preoperatively. Six patients (15%) had arterial calcification on their preoperative knee X-rays. Three patients (7.5%) had moderate PVD. There was no change in blood flow postoperatively in patients with or without PVD (p > 0.05). Vascular stenosis was less than 50% in all patients preoperatively and postoperatively. No postoperative vascular complications occurred. Severe PVD is not common in patients undergoing TKR. Performing total knee replacement under tourniquet control does not adversely affect the vasculature in patients with less than 50% vascular occlusion.


Increased feed supply and dietary fiber from sugar beet pulp improved energy retention in gestating sows.
The aim of the study was to investigate whether increased inclusion of sugar beet pulp (SBP) alters retention of fat, protein, and energy when backfat (BF) is restored in early- and mid-gestation. In total, 46 sows were fed one of four treatments with increasing inclusion of SBP with dietary fiber (DF) levels of 119, 152, 185, and 217 g/kg; sows were assigned to one of three feeding strategies (FS; high, medium, and low) depending on BF thickness at mating and again at day 30 for the following month. On days 0, 30, 60, and 108, body weight (BW) and BF thickness were measured, and body pools of protein and fat were estimated using the deuterium technique. On days 30 and 60, urine, feces, and blood samples were collected to quantify metabolites, energy, and N balances. On days 15 and 45, heart rates were recorded to estimate the heat production. At farrowing, total born and weight of the litter were recorded. In early gestation, BW gain (P < 0.01) and body protein retention increased (P < 0.05) with increasing fiber inclusion, while body fat retention increased numerically by 59%. Increase in BF was the greatest for sows fed the high FS, intermediate when fed the medium strategy, and negligible for sows fed the lowest FS. N intake, N loss in feces, and N balance increased linearly, whereas N loss in urine tended to decrease with increasing inclusion of fibers in early gestation. Concomitantly, fecal energy output and energy lost as methane increased linearly (P < 0.001), while energy output in urine declined linearly, and total metabolizable energy intake, therefore, increased from 40.5 MJ ME/d in the low-fiber group to 43.5 mega joule (MJ) metabolizable energy (ME)/d in the high-fiber group (P < 0.001). Changing the metabolizable energy toward more ketogenic energy was expected to favor fat retention rather than protein retention. However, due to increased intake of metabolizable energy and increased N efficiency with increasing fiber inclusion, the sows gained more weight and protein with increasing fiber inclusion. In conclusion, increased feed intake improved both fat and protein retention, whereas increased DF concentration increased protein retention.


Personality and risk perception in transport.
Within research on individual variations in risk perception, personality has been suggested as one important factor. In the present study, personality traits (44 items from the Big Five inventory) were investigated in relation to risk perception in transport and transport behavioural adaptations. In a sample of 312 participants, we found that the personality trait 'emotional stability versus neuroticism' was negatively correlated with risk perception (operationalised as "thinking about the possibility") of an accident (-0.38) and an unpleasant incident, such as crime, violence, robbery (-0.25). 'Agreeableness' was also negatively related to risk perception, however first and foremost in relation to perceived risk for unpleasant incidents on transport modes in which one interacts with other people (0.25). Moreover, regression analyses showed that 'emotional stability' was a significant predictor of behavioural adaptations on bus. Regression analyses explained between 17 and 26 percent of variance in behavioural adaptations. The results show that different groups of people vary systematically in their perception of risk in transport. Furthermore, these differences are manifest as a difference in risk-preventive behaviour at a strategic level, i.e. as decisions about avoiding risky situations.


Analysis of Fgf15 expression pattern in the mouse neural tube.
The dynamic process of neural tube regionalization in vertebrates is regulated by the expression of developmental genes which appear in characteristic patterns at neuroepithelial transversal domains, which are called secondary organizers. The molecular code present in these neuroepithelial organizers controls the generation of morphogenetic signals that induce and maintain regional characteristics in the surrounding neuroepithelium. The product of the Fgf8 gene is a secreted protein that has been demonstrated to be the key molecule for the isthmic organizer and is also expressed in two other organizer regions: the zona limitans and the anterior neural ridge. Here we analyze the expression of Fgf15 at different stages of mouse development in relation to Fgf8 and Otx2 expression patterns.


Metabolic syndrome is a risk factor for colorectal adenoma and cancer: a study in a White population using the harmonized criteria.
Metabolic syndrome (MetS) has been associated with colorectal adenomas and cancer. However, MetS definitions have changed over time, leading to a heterogeneity of patients included in previous studies and a substantial inextensibility of observations across time or eastern and western populations. Our aim was to evaluate the association of 'harmonized' criteria-defined MetS and its individual components with colorectal neoplasia and cancer in a western population. In this multicenter, cross-sectional study, we prospectively evaluated consecutive outpatients who underwent open-access colonoscopy over a 3-month period. MetS was diagnosed according to the 2009 'harmonized' criteria. Out of 5707 patients enrolled, we found 213 cancers (3.7%), 1614 polyps (28.3%), 240 nonpolypoid lesions (4.2%), 95 laterally spreading tumors (1.6%). Polyps presented histological low-grade dysplasia in 72.9% of samples, while in 9.8%, high-grade dysplasia or in situ carcinoma was present; dysplasia rates for nonpolypoid lesions were 66.2% (low-grade) and 2.9% (high-grade/in situ carcinoma), while for laterally spreading tumors, 29.6% and 37%, respectively. Overall, MetS prevalence was 41.6%. MetS correlated with both adenomas [odds ratio (OR): 1.76, 95% confidence interval (CI) 1.54-2.00] and cancer (OR: 1.92, 95% CI 1.42-2.58). MetS was the only risk factor for such colonic lesions in subjects younger than 50 years. For all colonic neoplasia, we found MetS and not its individual components to be significantly associated. MetS is risk factor for cancer and adenoma in Whites, especially when younger than 50 years. MetS patients might be considered as a high-risk population also in colorectal cancer screening programs.


Mechanical-biological treatment of municipal solid waste: Case study of 100 TPD Goa plant, India.
A long-term feasibility analysis of a 100 ton per day mechanical biological treatment (MBT) plant for municipal solid waste (MSW) valorization and material and energy recovery was carried out. It involves the material recovery and segregation stage (MRSS), organic extraction (pulping), thermophilic anaerobic digestion (AD), composting, effluent treatment plant (ETP), and biogas genset stages producing: 11.90% recyclables, 33% refused derived fuel (RDF), 5% compost of total waste received, 70 m3/day recyclable water and 0.435 MWh/day electricity. The biogas and methane yield were 0.535 and 0.350 m3/kg VSadded (avg.), respectively, with 40% VS removal (avg total solids (TS) 10%). Less than 3% (inert) of total waste received was subjected to landfill disposal. The MBT plant's revenue generation is 995 US$ per day/148 tons ($ 6.72/ton) waste processed. The gross OPEX is 24 US$/ton making the net OPEX of 17 US$/ton (minus revenue), which could be considered as the excellent OPEX for MSW based MBT plants as per global benchmarks. Further, local usage of RDF can significantly reduce the OPEX to 14 US$/ton, as almost 16% of the OPEX goes towards RDF disposal to cement companies located at a distance of 200-500 km from the MBT plant site. As per LCA study, the total GHG emissions have been calculated to be -25.68 tons CO2 eq./100 tons MSW. The negative emissions result from the export of electricity, compost, and RDF as well as recycling of paper and plastic products. Our study presents a cutting-edge scenario of all-inclusive recycling, recovery, and reuse loop of MSW direly required for accomplishing a circular economy.


SIgA-Shigella Immune Complexes Interact with Dectin-1 and SIGNR3 to Differentially Regulate Mouse Peyer's Patch and Mesenteric Lymph Node Dendritic Cell's Responsiveness.
In addition to contributing to immune exclusion at mucosal surfaces, secretory IgA (SIgA) made of polymeric IgA and secretory component is able to selectively reenter via microfold cells into Peyer's patches (PPs) present along the intestine and to associate with dendritic cells (DCs) of the CD11c+CD11b+MHCII+F4/80-CD8-phenotype in the subepithelial dome region and the draining mesenteric lymph nodes (MLNs). However, the nature of the receptor(s) for SIgA on murine PP and MLN DCs is unknown. We find that glycosylated secretory component moiety and polymeric IgA are both involved in the specific interaction with these cells. Using blocking antibodies and competition experiments, we identify Dectin-1 and specific intercellular adhesion molecule-3 grabbing non-integrin receptor 3 (SIGNR3) as receptors for SIgA. While SIgA-commensal immune complexes (ICs) contribute to local homeostasis upon interaction with mucosal DCs, the picture is less clear for pathogenic agents. We find that in comparison with incubation of Shigella flexneri alone, association of the enteropathogen with SIgA prompts freshly isolated DCs from PPs and MLNs to invert the production of pro- versus non-inflammatory cytokines/chemokines. The sum of the data suggests that in contrast to IgG-based ICs boosting immune reactivity of antigen-presenting cells, SIgA produced during an ongoing immune response can, in addition to its known function of immune exclusion, modulate mucosal DC conditioning via specific interaction with Dectin-1 and SIGNR3.


Childhood Adversities, Midlife Health, and Elder Abuse Victimization: A Longitudinal Analysis Based on Cumulative Disadvantage Theory.
Elder abuse victimization is increasingly recognized as a pressing public health concern. However, few empirical studies have investigated whether early life course adversities and midlife sequelae heighten risks for abuse in late life. Guided by cumulative disadvantage theory, the current study examined whether compromised health in middle adulthood (physical, psychological, cognitive) mediates the association between child abuse and elder abuse. This secondary analysis was based on data from the Wisconsin Longitudinal Study, a population-based, multi-wave dataset. We analyzed responses from 5,968 participants (mean age = 71 years; 54% female) on adapted versions of standardized measures: elder abuse victimization (outcome variable), childhood adversities (independent variable), and midlife health (physical health, depressive symptoms, cognitive functioning; mediator variables). Serial multiple mediation models were conducted, controlling for background characteristics. Rates for any elder abuse and child adversities were, respectively, 16.34% and 47.98%. Multivariate analyses supported the cumulative disadvantage hypothesis. Childhood adversities (0.11, p < .001) and midlife health (physical, -0.10, p < .05; depressive symptoms, 0.09, p < .001; cognitive functioning, 0.02, p < .05) had significant direct effects on elder abuse victimization. Childhood adversities also had an indirect effect on elder abuse through physical health (0.002, p < .05) and depressive symptoms (0.01, p < .001), both in serial. This innovative study advances our understanding mechanisms through which childhood trauma influences abuse in late life. Boosting health in middle adulthood could help prevent elder abuse. Other implications for clinical practice, treatment, and future research on elder abuse are discussed.


Evaluation of the antibacterial activity of selected Kenyan medicinal plant extract combinations against clinically important bacteria.
Infectious diseases are a major global public health concern as antimicrobial resistance (AMR) currently accounts for more than 700,000 deaths per year worldwide. The emergence and spread of resistant bacterial pathogens remain a key challenge in antibacterial chemotherapy. This study aims to investigate the antibacterial activity of combined extracts of various Kenyan medicinal plants against selected microorganisms of medical significance. The antibacterial activity of various extract combinations of Aloe secundiflora, Toddalia asiatica, Senna didymobotrya and Camelia sinensis against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Methicillin Resistant Staphylococcus aureus was assessed using the agar well diffusion and the minimum inhibitory concentration in-vitro assays. The checkerboard method was used to evaluate the interactions between the various extract combinations. ANOVA test followed by Tukey's post hoc multiple comparison test was used to determine statistically significant differences in activity (P < 0.05). At concentrations of 100 mg/ml (10,000 µg/well), the different combinations of the aqueous, methanol, dichloromethane and petroleum ether extracts of the selected Kenyan medicinal plants revealed diverse activity against all the test bacteria. The combination of methanolic C. sinensis and A. secundiflora was the most active against E. coli (14.17 ± 0.22 mm, diameter of zones of inhibition (DZI); MIC 2500 µg/well). The combination of methanolic C. sinensis and S. didymobotrya was the most active against S. aureus (16.43 ± 0.10 mm; MIC 1250 µg/well), K. pneumonia (14.93 ± 0.35 mm, DZI; MIC 1250 µg/well), P. aeruginosa (17.22 ± 0.41 mm, DZI; MIC 156.25 µg/well) and MRSA (19.91 ± 0.31 mm, DZI; MIC 1250 µg/well). The Minimum Inhibitory Concentration of the different plant extract combinations ranged from 10,000 µg/ well to 156.25 µg/well. The ANOVA test indicated statistically significant differences (P < 0.05) between single extracts and their combinations. The fractional inhibitory concentration indices (FICI) showed that the interactions were either synergistic (10.5%), additive (31.6%), indifferent (52.6%), or antagonistic (5.3%) for the selected combinations. This study findings validate the ethnopractice of selectively combining medicinal plants in the management of some bacterial infections in traditional medicine.


The Dismal State of Federal Funding for Experimental Evaluations of Interventions to Reduce Greenhouse Gas Emissions.
The threats of climate change to human well-being are well-documented and are growing in number and intensity. Despite the international community investing heavily in technological innovation and policy initiatives to solve the problem, emissions continue to rise. Experts are recognizing that eliminating emissions cannot be achieved without modifying the human behavior of which emissions are a function. However, little attention has been allocated to expanding the use of strategies developed by the behavioral-science community to reduce emissions on large scales. One possible reason is that federal funding has not been arranged to select such research. Therefore, we conducted an analysis of six sources of information about federal funding to fight climate change (the Government Accountability Office, the National Science Foundation, the Environmental Protection Agency, the Department of Energy, the National Institutes of Health, and the Center for Disease Control) and examined the extent to which they are funding behavioral science research to reduce emissions. Our results show an appalling lack of funding for behavioral science research to reduce emissions, especially experimental evaluations of strategies for reducing them. Implications and recommendations for funding of future research are discussed.


Phosphorylation of 9-beta-D-arabinofuranosylguanine monophosphate by Drosophila melanogaster guanylate kinase.
Nucleoside monophosphate kinases have an important role in the synthesis of nucleotides that are required for cellular metabolism. These enzymes are also important for the phosphorylation of nucleoside- and nucleotide analogs used in cancer and anti-viral therapy. We report the cDNA cloning and characterization of a 23 kDa guanylate kinase from Drosophila melanogaster (Dm-GUK). The predicted amino acid sequence was 58% identical to the human guanylate kinase and the enzyme was shown to phosphorylate GMP and dGMP with ATP as phosphate donor. The monophosphates of the deoxyguanosine analogs 2',2'-difluorodeoxyguanosine (dFdG) and 9-beta-D-arabinofuranosylguanine (araG) were also shown to be phosphorylated by the enzyme. We used the enzyme to reconstitute the complete in vitro three-step phosphorylation pathway for the conversion of dGuo and araG to the corresponding triphosphates.


Toxic effect of different ZnO particles on mouse alveolar macrophages.
To study the toxicity mechanism of ZnO nanoparticles on mouse macrophages, the toxic effect of different ZnO nanoparticles on mouse alveolar macrophages (MH-S) was investigated in this study. The results showed that the 24h IC(50) of four ZnO particles were 48.53, 47.37, 45.43 and 26.74 μg/ml for bulk ZnO, 100 nm, 30 nm and 10-30 nm ZnO particles, respectively. At the concentration of 10 μg/ml and below, dissolved zinc ions induced metallothionein synthesis, enhanced cellular resistance to oxidative stress. ZnO particles mainly induced cell apoptosis. When the concentration of ZnO particles was 20 μg/ml and above, excessive zinc destroyed mitochondrial function and cell membrane, caused cell necrosis. Dissolved zinc ions first cause toxicity in MH-S cells. However, the toxic effect of dissolved zinc ions may exist a threshold on mouse macrophages, inducing about 50% cell death. The toxic difference of different ZnO particles mainly depended on the effect of nondissolved ZnO particles.


[Catheterization of the vena cava superior via the internal jugular vein (author's transl)].
A method is described of introducing a catheter into the vena cava superior via the internal jugular vein. Possible complications and the experience gained with the method in 260 cases are discussed.


A four-week white bread diet does not alter plasma glucose concentrations, metabolic or vascular physiology in mourning doves, Zenaida macroura.
Birds are an enigma: their plasma glucose concentration is 1.5-2 times higher than similar-sized mammals, yet they do not normally exhibit symptoms of diabetes. We hypothesized that feeding adult mourning doves a refined carbohydrate diet (white bread: WB) for four weeks would raise plasma glucose concentrations and alter metabolic pathways and endothelial function when compared to birds receiving a nutritionally-balanced diet (bird seeds: SD). Following the four-week long diets, birds were euthanized, and cardiac blood, liver, and pectoralis muscles were collected for metabolomics analyses and biochemical assays. Cranial tibial arteries were dissected to measure acetylcholine-mediated vasodilation. Contrary to the hypothesis, WB-fed birds did not have increased plasma glucose concentrations. Principle component analysis score plots suggest minimal differences between groups. However, we identified 15 changes in individual metabolite concentrations between diet groups that, although not statistically significant, are highly predictive (area under receive operating curve, AUROC>0.90; number of highly predictive metabolites: 5 of 123 in plasma, 4 of 92 in liver, and 6 of 92 in pectoralis muscle). Moreover, pathway analyses revealed no significantly altered metabolic pathways between groups. Biochemical assays revealed no significant group differences in plasma uric acid and insulin, or pectoralis muscle glycogen concentrations. However, hepatic glycogen concentration was 2.12-fold higher in the WB group than in control doves (p = .015). Diet type did not influence vasodilation. In conclusion, a four-week long white bread diet increased liver glycogen but did not alter plasma glucose concentrations, metabolic or vascular physiology in mourning doves.


Complementary and Integrative Medicine in Pediatric Oncology - Development and Evaluation of a Blended Learning Program.
A blended learning program to promote the consultation expertise of pediatric oncologists (POs) on complementary and integrative medicine (CIM) was developed and completed by POs as part of a training program. A previous study indicated that POs in Germany were in need of information and training on CIM, and that there were no medical training offers on the subject in Germany. Evaluation of e-learning (questionnaires) and practically oriented one-day, face-to-face workshops (questionnaires, simulation patients), the workshops were evaluated with regard to changes in quality of physician-patient interaction and with regard of the participants' feedback. 32 POs signed up for the program and completed the e-learning. 22 POs participated in one of the workshops. POs agreed that they had received professionally relevant content during the e-learning. The questionnaires on physician-patient interaction showed neither clear positive nor negative changes concerning the quality of interaction. The feedback from the participants on the workshop was very positive. Following the end of the blended learning program the e-learning was made available again for interested POs. 34 further applications were received for participation in this part of the training program. With around 300 POs in Germany, this shows a high demand for further training offers of this kind as well as a need for further development.


Prognostic value of quantitative flow ratio measured immediately after drug-coated balloon angioplasty for in-stent restenosis.
This study aimed to evaluate prognostic value of quantitative flow ratio (QFR) in drug-coated balloon (DCB) angioplasty for in-stent restenosis (ISR). There is a high incidence of recurrent ISR after DCB angioplasty. QFR is a novel method for fast computation of fractional flow reserve for the target vessel based on quantitative coronary angiography (QCA) and fluid dynamics algorithms. Patients participating in the RESTORE ISR China randomized trial were enrolled and classified into the recurrent restenosis group and the non-recurrent restenosis group. The binary classifications followed the QCA standards of ISR. Clinical and angiographic characteristics of the groups were analyzed, and the QFRs before and after lesion preparation and after final DCB angioplasty were measured and compared. A total of 208 patients who underwent follow-up angiography were enrolled in the study, with 226 lesions measured in total. QFR value after DCB angioplasty (odds ratio [OR] 0.88; 95% confidence interval [CI] 0.83-0.93; p < .0001 for 1 mm increase), lesion length (OR: 1.08; 95% CI: 1.01-1.15; p = .017), and vessel caliber lumen diameter (OR: 0.35; 95% CI 0.13-0.89; p = .027) were independently associated with recurrent restenosis after DCB angioplasty. The optimal QFR cut-off value was determined to be 0.90 with a sensitivity of 0.94, specificity of 0.56, and accuracy of 0.79 in predicting recurrent restenosis. The QFR value after DCB angioplasty is a promising predictor of DES ISR.


Wheezing trajectories from childhood to adulthood in a population-based cohort.
Wheezing may lead to asthma and reduced pulmonary function in later life. The study aims to identify wheezing trajectories and investigate their relation with pulmonary function and asthma-related outcomes at 22 years of age. Individuals from a population-based cohort in Brazil (1993 Pelotas Birth Cohort) with post-bronchodilator pulmonary function data at 22 years (3350) were included in the study. From parentally reported (4 and 11 years) and self-reported (15, 18 and 22 years) history of wheezing in the last 12 months, we used a group-based trajectory modelling approach to derive wheezing trajectories. Four trajectories were identified: never/infrequent, transient-early, late-onset and persistent wheeze. After adjustments, wheezing trajectories remained associated with lower post-bronchodilator values of pulmonary function. Individuals in the persistent wheeze trajectory had a markedly poorer pulmonary function and also showed greater odds of asthma-related outcomes compared to other trajectories groups. Those following this trajectory had on average -109 ml (95% CI: -188; -35), -1.80 percentage points (95% CI: -2.73; -0.87) and -316 ml/s (95% CI: -482; -150) lower FEV1, FEV1/FVC ratio and FEF25-75% respectively; higher odds of self-reported medical diagnosis of allergy (OR 6.18; 95% CI: 3.59; 10.61) and asthma (OR 12.88; 95% CI: 8.91; 18.61) and asthma medication use (OR 9.42; 95% CI: 5.27; 16.87) compared to the never/infrequent group. Wheezing trajectories, especially the persistent wheeze trajectory, were related to lower pulmonary function values and increased risk of asthma and allergy diagnosis in early adulthood.


Extraction of scandium from bauxite residue by high-pressure leaching in sulfuric acid solution.
Rare earth elements, such as yttrium, scandium, neodymium, and praseodymium, have been reported to be associated with minerals in bauxite and transferred to the refining residue when bauxite is refined to alumina (Al2O3) by Bayer Process. In terms of price, scandium is the most valuable rare-earth element in bauxite residue. This research discusses the effectiveness of scandium extraction from the bauxite residue through pressure leaching in sulfuric acid solution. The method was selected to obtain high scandium recovery and leaching selectivity to iron and aluminium. Series of leaching experiments were conducted under variations of H2SO4 concentration (0.5-1.5 M), leaching duration (1-4 h), leaching temperature (200-240 °C), and slurry density (10-30% (w/w)). Taguchi method with L9:34 orthogonal array was adopted to design the experiments. Analysis of Variance (ANOVA) was performed to determine the most influential variables of the extracted scandium. The experimental result and statistical analysis revealed that the optimum condition for scandium extraction was at 1.5 M H2SO4, a leaching duration of 1 h, a temperature of 200 °C, and a slurry density of 30% (w/w). The leaching experiment carried out at this optimum condition resulted in scandium extraction of 90.97% and co-extracted iron and aluminium of 32.44% and 75.23%, respectively. Analysis of Variance showed that solid/liquid ratio was the most influential variable with a contribution of 62%, followed by acid concentration (21.2%), temperature (16.4%), and leaching duration (0.3%).


Intrabiliary MR imaging.
The goal of this research is to illustrate the potential role of interventional MR imaging ina clinical setting. As shown by this study, IBMR is feasible, is well tolerated, and positively affects patient management. IBMR allowed for significantly decreased field of view and high in-plane resolution and provided contrast between the biliary lumen and adjacent structures with high diagnostic accuracy. This technique enabled clinicians not only to improve imaging of the biliary tree but also to make a more accurate diagnosis. Based on this pilot work, there are several potential avenues of further expansion for IBMR. For example, enhanced imaging of the biliary tree may allow for monitoring of new biliary treatment regimens such as photodynamic therapy or molecular targeting. In addition, this technique may also foster development of innovative new percutaneous procedures that may eventually treat some biliary disorders under MR imaging guidance.


Prediction of local strength of ascending thoracic aortic aneurysms.
Knowledges of both local stress and strength are needed for a reliable evaluation of the rupture risk for ascending thoracic aortic aneurysm (ATAA). In this study, machine learning is applied to predict the local strength of ATAA tissues based on tension-strain data collected through in vitro inflation tests on tissue samples. Inputs to machine learning models are tension, strain, slope, and curvature values at two points on the low strain region of the tension-strain curve. The models are trained using data from locations where the tissue ruptured, and subsequently applied to data from intact sites to predict the local rupture strength. The predicted strengths are compared with the known strength at rupture sites as well as the highest tension the tissues experienced at the intact sites. A local rupture index, which is the ratio of the end tension to the predicted rupture strength, is computed. The 'hot spots' of the rupture index are found to match the rupture sites better than those of the peak tension. The study suggests that the strength of ATAA tissue could be reliably predicted from early phase response features defined in this work.


Additive effects of norepinephrine and cyclic AMP on the activation of the protein kinase from adipose tissue.
In this work the kinetics of activation of the cyclic AMP-dependent protein kinase by several catecholamines and ACTH, have been studied in rat epididymal fat pads and isolated fat cells. The method of Soderling and co-workers which permits the measurement of the state of activation of the protein kinase after hormonal stimulation in adipose tissue, has been used. Kinetics experiments where norepinephrine was used showed that the results obtained with isolated cells conform to the models of Sutherland and Brostrom and co-workers. Wtih intact tissue, norepinephrine not only stimulates the protein kinase activity measured without exogenous cyclic AMP but also the total activity measured in the presence of cyclic AMP (5 X 10(-6) M); thus the effect of norepinephrine, obtained during incubation of the tissue, and that of cyclic AMP, added to the soluble fraction after incubation, were additive. This effect seems to be of the beta type because it is blocked completely by propranolol. A weak, additive but significant effect was also obtained with epinephrine and isoproterenol but not with ACTH. Neither cyclic GMP nor cyclic IMP seems implicated in this effect. It was shown that stroma vascular cells which are present in the fat pads are not involved. These results suggest that the effects of norepinephrine on the protein kinase of the fat pads cannot be completely explained by the model of Brostrom and colleagues.


pH analysis of still and carbonated bottled water: Potential influence on dental erosion.
To assess pH values to characterize bottled water in Portugal, being able to provide information for both patients and clinicians about its erosive potential, as a tool to prevent the ingrowing prevalence of dental erosion and its progression, especially in patients who are at greater risk, such as those with dry mouth syndrome, making the dissemination of this knowledge a fundamental tool for clinical decision. One hundred and five common brands of bottled water (n = 105), commercialized in Portugal, were analyzed. Of these, 73 were smooth water (Group A) and 32 carbonated water (Group B). All pH values were assessed by potentiometric measurement with a calibrated electrode. For each brand, five independent measurements were recorded at 25°C for further calculation of the mean pH value and standard deviation. Focusing on the mean pH values from Group A, one had a pH mean value lower than 5.2, four between 5.2 and 5.5, thirty-seven between 5.5 and 6.8, and thirty-one higher than 6.8. In Group B, ten had a mean pH value lower than 5.2, ten between 5.2 and 5.5, twelve between 5.5 and 6.8, and none above 6.8. Bottled water, commercialized in Portugal, has different mean pH values, some below the critical threshold of enamel and/or dentin, suggesting that they may have a greater risk of consumption than others, only with respect to the pH parameter of erosive potential. Further investigation concerning this area is needed for wider conclusions.


Evaluation of the timing of the booster injection after a primary vaccination against hepatitis A.
To evaluate the long-term efficacy and the timing of booster injection of a lyophilized, inactivated hepatitis A vaccine (HAV), we studied the acquired anti-hepatitis A virus titres in 45 subjects who received either two or three doses of the vaccine. With three doses > or = 0.5 microgram administered at 0, 1 and 6 months, antibody titres increased to approximately half those seen in people with a history of natural hepatitis A infection. Although the titres decreased gradually, all subjects remained anti-HAV positive at least 5 years after the third injection. The geometric mean titre exceeded 100 mIU/mL, which approximated the highest titre obtainable by the inoculation of immune serum globulin. A prompt antibody reaction was seen with two doses administered 2 weeks apart, with the titres achieved being 5.6-fold the peak titres obtained by the inoculation of immune serum globulin. All 33 subjects were antibody positive 18 months after the first injection, but some became seronegative by 30 months, suggesting that a third booster dose would be desirable at 18 months.


Late ureteral conduit urinary leak as a presentation of urothelial carcinoma of the ureter.
Urinary leakage at the ureteroenteric anastomosis in patients with urinary diversion is a rare complication that usually occurs in the early postoperative period, regardless of the indication for surgery. To our knowledge, ureteroenteric urinary leaks that occur late in the postoperative period have not been described. We present a unique case of a late ureteroenteric anastomotic leak within an ileal conduit that occurred as a result of recurrent urothelial carcinoma of the ureter at the site of anastomosis.


Coexistence of Anti Neutrophilic Cytoplasmic Antibody (ANCA) Negative Renal Limited Vasculitis and Atypical- Hemolytic Uremic Syndrome (aHUS).
Small vessel necrotizing vasculitis is divided into two groups; Immune complex mediated and Pauci immune vasculitis. Hemolytic uremic syndrome (HUS) is a rare disease manifested as microangiopathic hemolytic anemia, thrombocytopenia and renal involvement. The coexistence of ANCA negative vasculitis and atypical HUS (aHUS) is rare. We describe a case of a 40 years old lady with rapidly declining kidney function. Renal Biopsy revealed Crescentic necrotizing glomerulonephritis (CGN). She was treated with plasmapheresis alternating with hemodialysis (HD) and immunosuppressive therapy. One month later she developed hemolytic anemia with peripheral schistocytes and thrombocytopenia and diagnosed as aHUS. Same treatment continued and her aHUS resolved spontaneously over one week. However her kidney functions didn't improve and ended up with end stage renal disease (ESRD). DOI: 10.52547/ijkd.6443.


[Genetic determinants of cardiovascular remodeling in Uzbek patients with essential hypertension].
To study distribution of the incidence of polymorphic markers of the genes ACE (I/D), ANG (M235T), AT1R (A1166C), CYP11B2 (T344C) in patients with essential hypertension (EH) of Uzbek nationality; to determine carriage of gene combinations with detection of most unfavourable combinations associated with severity of cardiovascular remodeling. We examined 172 Uzbek males with EH of the second-third degree, mean age 49.4 +/- 7.8 years, mean duration of EH 6.5 +/- 5.1 years. Polymorphism I/D, A1166C, M235T, T344C of genes ACE, AT1R, ANG, CYP11B2, respectively, was revealed in all the patients. The control group consisted of 60 Uzbek males matched by age. We performed echocardiography, duplex scanning of carotid arteries, dopplerography of the brachial artery, IEMA measurement of the level of vascular adhesion molecule VCAM-1S in blood serum, microalbuminuria in Micral-test. We isolated genome DNA, amplified polymorphic gene regions and analysed products of polymerase chain reaction. Distribution of polymorphic markers of the genes ACE, CYP11B2, ANG, AT1R in EH Uzbek patients corresponds to this in Europeans. In most cases (95.4%) there was primarily combined carriage of "destroying" alleles of the genes of renin-angiotensin-aldosteron system associated with synergetic impact on development of left ventricular hypertrophy (LVH) and vascular remodeling; combination of alleles D+235T is most unfavourable in relation to severity of LVH, vasoregulatory endothelial dysfunction and is associated with the highest thickness of intima-media complex of the carotid artery. The role of 235T allele of ANG gene is most important in development of LVH. Severity of vasoregulatory endothelial dysfunction is associated with carriage of both 235T allele of ANG gene and 1166C allele of AT1R gene, in the latter case aggravated by significant adhesion of vascular endothelium. Progression of atherosclerotic affection of the carotid arteries is associated more with carriage of D allele of ACE gene.


Lamprey immune protein triggers the ferroptosis pathway during zebrafish embryonic development.
Previously, a novel lamprey immune protein (LIP) was identified, which plays an important role in immunity and the regulation of growth and development in lampreys. However, the mechanism of how LIP regulates growth and development remains unclear. In this study, a zebrafish model of LIP overexpression was established by delivering a transgenic plasmid to the fertilized egg. The biological function of LIP was explored in vivo through phenotypic characterization, comparative transcriptome sequencing, and physiological and biochemical analyses. LIP caused developmental toxicity in zebrafish, increased embryo mortality and exhibited strong teratogenic, lethal, and developmental inhibitory effects. Comparative transcriptome analysis showed that LIP-induced large-scale cell death by triggering ferroptosis. Furthermore, LIP-induced lipid peroxidation and caused pericardial edema. Direct inhibition of acsl4a and tfr1a, or silencing of acsl4a and tfr1a with specific siRNA suppressed ferroptosis and pericardial edema. Taken together, we confirmed that LIP can participate in growth and development via the regulation of lipid peroxidation and ferroptosis. This lays the foundation for future studies on the function of LIP in lampreys. Video Abstract.


[Action of broken fractions of regeneration blastema on the synthetic activity of posterior fragments or Dendrocelum lacteum cut behind the pharynx].
Pounded blastemas of regeneration favour RNA synthesis is neoblasts of posterior parts of Dendrocoelum lacteum, cut behind the pharynx, which normally fail to regenerate a head; and induce excrescences. Fixed parenchyma cells and other differentiated tissues do not synthesize RNA with pounded blastemas.


Surgical treatment in Paget's disease with invasive ductal carcinoma: an observational study based on SEER.
The aim is to analyse the clinical presentation, treatment and outcomes in patients with Paget's disease with invasive ductal carcinoma (PD-IDC), with special emphasis on the role of surgical treatment. Using data obtained by the Surveillance, Epidemiology, and End Results (SEER) program from 2010-2013, we investigated the differences in characteristics, overall survival (OS), and breast cancer-specific mortality (BCSM) between patients with PD-IDC and those with invasive ductal carcinoma (IDC). Compared with IDC group, patients with PD-IDC had a better prognosis and lower mortality in adjusted analyses. In the multivariate analysis of cases with PD-IDC, history of ALND was significantly associated with OS while Her2 status were associated with BCSM. Further, subgroup analysis demonstrated no difference between surgical treatment subgroups for either OS or BCSM. The results demonstrated that PD-IDC appears to alter the association between prognosis and Her2 status. Meanwhile, breast-conserving surgery with radiotherapy may be a feasible treatment alternative and sentinel lymph node biopsy should be considered as an appropriate treatment for patients with PD-IDC.


Could CT abdomen and PET/CT be helpful in early diagnosis of Whipple's disease? A case report.
Whipple's disease is a rare disease, which can be fatal if not treated. It is often diagnosed at a late stage because of the varied disease presentation and its rare incidence. Classic Whipple's disease presents with arthralgia, abdominal pain, diarrhea and weight loss. CT abdomen may show mesenteric lymphadenopathy with hypodense centers. These CT findings along with clinical presentation should prompt early diagnosis of Whipple's disease. We present a case of classic Whipple's disease with interesting CT abdomen and PET scan findings.


Nonrandom distribution of exchange points in patients with reciprocal translocations.
A total of 770 breakpoints (80 of them identified by the authors) from unrelated patients with two-break rearrangements resulting in reciprocal translocations were studied to determine whether they were located preferentially. The distribution of breakpoints among the chromosome arms differs from that expected on the basis of their lengths, with more than expected on chromosome arms 4p, 9p, 9q, 13q, 18q, 21p, 21q, 22p, and 22q and fewer than expected on 1p, 1q, 3p, 3q, 5q, 6q, 7p, 12p, 16p, and the gonosomes. More breakpoints than expected occurred in the centromeric regions, and fewer in the median regions. Distribution of breakpoints within bands differed with the technique used: with G banding a many more breakpoints were localized in the light bands and fewer in the dark bands. With R banding no fewer than expected were present in the light bands and only slightly more were found in the dark bands.


Role of marrow stromal cells in the establishment of a transformed lymphoblastic B-cell line from a normal human subject.
A monoclonal human B-lymphoblastoid cell line (UTMB-460) arose spontaneously from the bone marrow of a normal healthy woman who was seropositive for an EB-virus infection. Chromosomally, the UTMB-460 cells are near tetraploid, with a specific translocation (8;9) (p11.2; p24), and have surface IgMk. The UTMB-460 cells are resistant to killing in vitro by spontaneous and rIFN alpha 2 and rIL-2 stimulated NK cells from the patient and other normal subjects, but are killed by lymphokine activated killer cells. The index patient has not developed leukemia/lymphoma during the follow-up interval of 22 months. The growth of UTMB-460 cells is supported by undefined growth factors in FCS and by BCGF in the absence of FCS. rIL-2 stimulates DNA synthesis by UTMB-460 cells. The UTMB-460 cells were adherent to the normal MSC in the primary culture and show specific heterotypic adherence to normal MSC when compared to skin fibroblasts. In addition, 6/6 normal marrow stromal cells and 4/6 normal skin fibroblasts induced growth of colonies from UTMB-460 cells. These data suggest that MSC interacted with the transformed cells (UTMB-460) in vitro and played a critical role in the establishment of the UTMB-460 cell line.


Hesperetin derivative-14 alleviates inflammation by activating PPAR-γ in mice with CCl4-induced acute liver injury and LPS-treated RAW264.7 cells.
Hesperetin is a flavanone glycoside compound naturally occurring in the fruit peel of Citrusaurantium L. (Rutaceae). Previous studies revealed that hesperetin possesses various pharmacological effects, including anti-inflammation, anti-tumor, anti-oxidant and neuroprotective properties. Hesperetin derivative-14 (HD-14) is a derivative of hesperetin improved in water solubility and bioavailability. In this study, we indicated that HD-14 (2μM) significantly attenuated inflammation in LPS-treated RAW264.7 cells, besides, HD-14 (100mg/kg) exhibited hepato-protective effects and anti-inflammatory effects on C57BL/6J mice with CCl4-induced acute liver injury. In addition, it was demonstrated that HD-14 dramatically up-regulated the expression of PPAR-γ in vivo and in vitro. Interestingly, over-expression of PPAR-γ had anti-inflammatory effects on the expressions of TNF-α, IL-6, and IL-1β, whereas, knockdown of PPAR-γ with small interfering RNA had pro-inflammatory effects in LPS-treated RAW264.7 cells. Thus, our findings demonstrated that HD-14 alleviated inflammation by activating PPAR-γ expression at least in part. Further studies founded that HD-14 remarkably inhibited the expression of p-JAK1 and p-STAT1 through up-regulating PPAR-γ. Together, these results suggested that HD-14 served as an activator of PPAR-γ and the JAK1/STAT1 signaling pathway may be involved in the progress of inflammation. Collectively, HD-14 may be utilized as a potential anti-inflammation monomeric compound in the treatment of acute liver injury.


Studies of the Epstein-Barr virus receptor found on Raji cells. I. Extraction of receptor and preparation of anti-receptor antibody.
Raji, a human lymphoblastoid cell line, expresses a membrane receptor (EBVR) specific for Epstein Barr virus (EBV). A component that binds EBV was extracted from this cell line by treatment of the cells for 3 hr on ice with Tris buffer containing 10% glycerol. The treatment reduced the capacity of the cells to bind virus, and after concentration the receptor extract (RE) inhibited both EBV binding and superinfection of fresh Raji cells. Similarly prepared extracts of EBVR- cells lacked such activity. An antibody was made to the extract (anti-RE), which after absorption with EBVR- cells, bound to the same percentages of EBVR+ lymphoblastoid cell lines, EBVR+ human/mouse somatic cell hybrids, and fresh peripheral B cells as the virus did. In reciprocal assays, preincubation of EBVR+ cells with anti-RE inhibited virus binding. Doubly stained patches were observed on membranes of EBVR+ cells that had been incubated simultaneously with virus and anti-RE and stained respectively with rhodaminated and fluoresceinated reagents. The major polypeptide immunoprecipitated by anti-RE from radiolabeled Raji cells had an approximate calculated m.w. of 150,000.


Molecular mechanisms of action determine inhibition of paroxysmal depolarizing shifts by NMDA receptor antagonists in rat cortical neurons.
N-methyl-d-aspartate glutamate receptors (NMDARs) are involved in numerous central nervous system (CNS) processes, including epileptiform activity. We used a picrotoxin-induced epileptiform activity model to compare the action of different types of NMDAR antagonists in rat brain slices. Paroxysmal depolarizing shifts (PDS) were evoked by external stimulation in the medial prefrontal cortex (mPFC) slices and recorded in pyramidal cells (PC) and in fast-spiking interneurons (FSI). The NMDAR antagonists APV and memantine reduced the duration of PDS. However, the competitive antagonist APV caused similar effects on the PC and FSI, while the open-channel blocker memantine had a much stronger effect on the PDS in the FSI than in the PC. This difference cannot be explained by a corresponding difference in NMDAR sensitivity to memantine because the drug inhibited the excitatory postsynaptic current (EPSC) similarly in both cell types. Importantly, the PDS were significantly longer in the FSI than in the PC. The degree of PDS inhibition by memantine correlated with individual PDS durations in each cell type. Computer modeling of a synaptic network in the mPFC suggests that the different effects of memantine on the PDS in the PC and FSI can be explained by use dependence of its action. An open-channel blocking mechanism and competition with Mg2+ ions for the binding site result in pronounced inhibition of the long PDS, whereas the short PDS are weakly sensitive. Our results show that peculiarities of kinetics and the mechanism of action largely determine the effects of NMDAR antagonists on physiological and/or pathological processes.


Complications of intravenous therapy with steel needles and Teflon catheters. A comparative study.
Complications of intravenous therapy with steel needles and small-bore Teflon catheters were compared in a randomized study of 954 cannula insertions. Cannulas were inserted and cared for by an intravenous team following a standard protocol. There were no cases of cannula-related septicemia and only one case of local infection, a cellulitis in the group in which Teflon catheters were used. There was a low incidence of positive semiquantitative cannula cultures in both treatment groups (steel needles 1.5 percent, Teflon catheters 1.4 percent). The risk of phlebitis was significantly greater with Teflon catheters (18.8 percent with Teflon catheters, 8.8 percent with steel needles, adjusted odds ratio 1.87). Steel needles were significantly associated with infiltration (17.9 percent with Teflon catheters, 40.1 percent with steel needles, adjusted odds ratio 0.39). The over-all rate of complications was significantly greater for the group in which steel needles were used (53.8 versus 64.0 percent, adjusted odds ratio 0.72), principally due to the increased risk of infiltration with steel needles. Analysis of the per day risk of infiltration and phlebitis revealed that these relationships were present for each day the cannulas remained in place. We conclude (1) that steel needles and small-bore Teflon catheters can both be used with low risk of infection and (2) that Teflon catheters more frequently cause phlebitis, whereas steel needles infiltrate more readily.


Synthesis and infectivity of vesicular stomatitis virus containing nonglycosylated G protein.
The replication of vesicular stomatitis virus (VSV) is inhibited by tunicamycin (TM), an antibiotic that blocks the formation of N-acetylglucosaminelipid intermediates. We had shown previously that the viral glycoprotein (G) synthesized in cells treated with TM is not glycosylated and is not found on the outer surface of the cell plasma membrane. In this report, we shown that cells exposed to TM produce a low yield of infectious particles. The yield is increased when the temperature during infection is lowered from 37 to 30 degrees C. At 30 degrees C in the presence of TM, both wild-type VSV and the temperature-sensitive mutant ts045 produce particles that do not bind to concanavalin A Sepharose and contain only the nonglycosylated form of G. These particles have a specific infectivity (pfu/cpm) comparable to that of VSV containing glycosylated G.


Transfected adenosine A1 receptor-mediated modulation of thrombin-stimulated phospholipase C and phospholipase A2 activity in CHO cells.
Thrombin receptor activation in Chinese hamster ovary (CHO) cells stimulates the hydrolysis of inositol phospholipids and the release of arachidonic acid. Our previous studies have shown that activation of the human transfected adenosine A1 receptor in CHO cells (CHO-A1) potentiates the accumulation of inositol phosphates elicited by endogenous P2U purinoceptors and CCKA receptors. In this study we have investigated whether adenosine A1 receptor activation can modulate thrombin-stimulated arachidonic acid release and/or inositol phospholipid hydrolysis in CHO-A1 cells. Thrombin stimulated [3H]arachidonic acid release and total [3H]inositol phosphate accumulation in CHO-A1 cells. Both these responses to thrombin were were insensitive to pertussis toxin. The protein kinase C activator, phorbol 12-myristate 13-acetate (PMA), potentiated thrombin-stimulated [3H]arachidonic acid. In marked contrast, PMA inhibited thrombin-stimulated [3H]inositol phosphate accumulation. The selective protein kinase C inhibitor Ro 31-8220 (3-¿1-[3-(2-isothioureido)propyl] indol-3-yl¿-4-(1-methylindol-3-yl)-3-pyrrolin-2,5-dione) had no effect on thrombin-stimulated [3H]arachidonic acid release but reversed the potentiation of thrombin-stimulated [3H]arachidonic acid release elicited by PMA. The selective adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) augmented the release of [3H]arachidonic acid produced by thrombin. Co-activation of the adenosine A1 receptor also potentiated thrombin-stimulated [3H]inositol phosphate accumulation. The synergistic interactions between the adenosine A1 receptor and thrombin were abolished in pertussis-toxin-treated cells. The potentiation of [3H]arachidonic acid release by CPA was blocked by the protein kinase C inhibitors Ro 31-8220 and GF 109203X (3-[1-[3-(dimethylamino)propyl]-1 H-indol-3-yl]-4-(1 H-indol-3-yl)- 1H-pyrrole-2,5-dione). In conclusion, thrombin receptor activation in CHO-A1 cells stimulates the accumulation of [3H]inositol phosphates and the release of [3H]arachidonic acid through pertussis-toxin-insensitive G-proteins. Experiments using PMA suggest that protein kinase C differentially regulates thrombin receptor activation of phospholipase C and phospholipase A2. Co-activation of the transfected human adenosine A1 receptor augments thrombin-stimulated phospholipase C and phospholipase A2 activity. Finally, the augmentation of phospholipase A2 activity by the adenosine A1 receptor is inhibited by selective protein kinase C inhibitors, suggesting the involvement of protein kinase C.


Acute infantile thalamic necrosis.
An acute encephalopathy of infancy presenting as seizures and coma following a presumably infectious disease with the distinctive finding of thalamic necrosis was recently described. The authors report a similar case in an 11-month-old infant, and discuss its possible pathogenesis.


Survival Before and After Direct Surgical Quality Feedback in a Population-Based Lung Cancer Cohort.
Surgical resection is the main curative modality for non-small cell lung cancer (NSCLC), but variation in the quality of care contributes to suboptimal survival rates. Improving surgical outcomes by eliminating quality deficits is a key strategy for improving population-level lung cancer survival. We evaluated the long-term survival effect of providing direct feedback on institutional performance in a population-based cohort. The Mid-South Quality of Surgical Resection cohort includes all NSCLC resections at 11 hospitals in four contiguous Dartmouth Hospital Referral Regions in Arkansas, Mississippi, and Tennessee. We evaluated resections from 2004 to 2013, before and after onset of a benchmarked performance feedback campaign to surgery and pathology teams in 2009. We evaluated 2,206 patients: 56% preintervention (pre-era) and 44% postintervention (post-era). Preoperative positron emission tomography/computed tomography (46% vs 82%, p < 0.0001), brain scans (6% vs 21%, p < 0.0001), and bronchoscopy (8% vs 27%, p < 0.0001) were more frequently used in the post-era. Patients had 5-year survival of 47% (44% to 50%) in the pre-era compared with 53% (50% to 56%) in the post-era (p = 0.0028). The post-era had an adjusted hazard ratio of 0.85 (95% confidence interval [CI], 0.75 to 0.97; p = 0.0158) compared with the pre-era. This differed by extent of resection (p = 0.0113): compared with the pre-era, the post-era adjusted hazard ratio was 0.49 (95% CI, 0.33 to 0.72) in pneumonectomy, 0.91 (95% CI, 0.79 to 1.05) in lobectomy/bilobectomy, and 0.85 (95% CI, 0.63 to 1.15) in segmentectomy/wedge resections. Overall survival after surgical resection improved significantly in a high lung cancer mortality region of the United States. Reasons may include better selection of patients for pneumonectomy and more thorough staging.


(8S,9S,10R)-4-(4-Chloro-benz-yloxy)-7,8-didehydro-3,7-dimeth-oxy-17-methyl-morphinan-6-one monohydrate.
In the title compound, C(26)H(28)Cl(N)O(4)·H(2)O, the dihedral angle betwene the two aromatic rings is 69.73 (6)°. The N-containing ring exhibits a chair conformation, while the other non-aromatic rings are in approximate envelope conformations. In the crystal, the water mol-ecule forms O-H⋯O and O-H⋯N hydrogen bonds and a C-H⋯O link also occurs.


A DNA fingerprinting system for the ectoparasite Sarcoptes scabiei.
We describe multiple hypervariable microsatellites that will provide a highly informative genetic marker system for the sarcoptid mite Sarcoptes scabiei. Eighteen positive clones containing the highly repetitive sequence (GA)n were isolated from a partial genomic library of S. scabiei. Ten of these clones were characterised by sequencing and primers were designed from the unique sequences flanking eight microsatellite loci. Genomic DNA was subsequently extracted from individual mites and the repeat blocks were amplified by way of [gamma 33P] ATP end-labelled polymerase chain reaction. Fragment length polymorphisms were revealed in three of the loci when resolved on polyacrylamide sequencing gels. The high levels of allelic variability demonstrated between individual mites enable these three loci to form a DNA fingerprinting system that will be suitable for epidemiological and taxonomic studies both within and between host species.


Frontal EEG delta/alpha ratio and screening for post-stroke cognitive deficits: the power of four electrodes.
This study analysed correlations between post-stroke, quantitative electroencephalographic (QEEG) indices, and cognition-specific, functional outcome measures. Results were compared between QEEG indices calculated from the standard 19 versus 4 frontal (or 4 posterior) electrodes to assess the feasibility and efficacy of employing a reduced electrode montage. Resting-state EEG was recorded at the bedside within 62-101 h after onset of symptoms of middle cerebral artery, ischaemic stroke (confirmed radiologically). Relative power for delta, theta, alpha and beta, delta/alpha ratio (DAR) and pairwise-derived brain symmetry index (pdBSI) were averaged; over all electrodes (global), over F3, F4, F7, F8 (frontal) and P3, P4, T5, T6 (posterior). The functional independence measure and functional assessment measure (FIM-FAM) was administered at mean 105 days post-stroke. Total (30 items) and cognition-specific (5 items) FIM-FAM scores were correlated with QEEG indices using Spearman's coefficient, with a Bonferroni correction. Twenty-five patients were recruited, 4 died within 3 months and 1 was lost to follow-up. Hence 20 cases (10 female; 9 left hemisphere; mean age 68 years, range 38-84) were analysed. Two QEEG indices demonstrated highly-significant correlations with cognitive outcomes: frontal DAR (ρ = -0.664, p ≤ 0.001) and global, relative alpha power (ρ = 0.67, p ≤ 0.001). After correction there were no other significant correlations. Alpha activity - particularly frontally - may index post-stroke attentional capacity, which appears to be a key determinant of functional and cognitive outcomes. Likewise frontal delta pathophysiology influences such outcomes. Pending further studies, DAR from 4 frontal electrodes may inform early screening for post-MCA stroke cognitive deficits, and thereby, clinical decisions.


Cholesteryl ester hydrolase activity in human symptomatic atherosclerosis.
Acid cholesteryl ester hydrolase (CEH) activity was assayed in mononuclear cells of patients with symptomatic atherosclerosis (transient ischemic attacks, TIA) and in age-matched controls showing no evidence of atherosclerosis. The acid CEH level of TIA patients was significantly lower than that of controls (1074 +/- 128 vs 2113 +/- 255 pmol/mg P/hr, mean +/- SE). Neither mononuclear cell nor plasma cholesterol and cholesteryl ester concentrations differed significantly between atherosclerotic and control groups. TIA women had lower mononuclear cell concentrations of free cholesterol than men.


Diet and calorie restriction.
Current data suggest that the life spans of commonly held rodent species have decreased and the occurrence of tumors occurs earlier in the lifespan of ad libitum-fed animals. The most likely cause of this change in the life span of barrier-reared genetically defined animals is increased body weight. The effects of caloric restriction on a variety of functional measures and on age-dependent tumors and lesions are the focus of this presentation. Recommendations for caloric restriction, or at least "dietary control," will be discussed.


Sodium butyrate alleviates intestinal injury and microbial flora disturbance induced by lipopolysaccharides in rats.
Bacterial endotoxin invasion reduces intestinal barrier functions, such as intestinal bacterial translocation and enteric infection. In this study, we investigated whether sodium butyrate (NaB) alleviates lipopolysaccharide (LPS)-induced inflammation by reducing intestinal damage and regulating the microflora. Rats were divided into four groups for the intraperitoneal injection of LPSs and intragastric gavage with NaB: Con, LPS, LPS + NaB, and NaB. The results showed that NaB alleviated intestinal villus injury and inflammatory infiltration caused by LPS. NaB supplementation decreased the mRNA levels of toll-like receptor (TLR)-4, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and the trend was most pronounced in the jejunum. The morphology of the intestinal nucleus and mitochondria was further observed by transmission electron microscopy. The results showed that NaB supplementation alleviated LPS-induced nuclear atrophy, apoptosis, mitochondrial damage, and rupture. Moreover, NaB improved the LPS-induced inflammatory response by regulating the intestinal barrier. Furthermore, 16S rRNA sequencing showed that the LPS increased the abundance of the harmful bacterium Bacteroides, while the abundance of beneficial bacteria decreased. In the LPS + NaB group, the intestinal microbiota destroyed by the LPS was rebalanced, including a decrease in Bacteroides and an increase in Bifidobacterium and Odoribacter. In conclusion, NaB alleviates LPS-induced enteritis by regulating inflammatory cytokines, maintaining the mucosal barrier, and restoring the microbiota changes.


Intramedullary reamings for the histological diagnosis of suspected pathological fractures.
The aim of this study was to evaluate how effective reamings taken at the time of surgery for fracture were in the diagnosis of malignancy. All histology reports over a five-year period were examined. Ninety cases, where reamings were taken, were identified and included. Reamings are commonly sent for histological diagnosis in orthopaedic practice. A definitive tissue diagnosis was established in 55 samples (60%). No diagnosis was established in 30 (33%), as the tissue sample was deemed inadequate, 17 of which were known to have a malignancy elsewhere. Five case reports were lost. The process by which the bone samples were obtained is believed to be very destructive, making histological diagnosis difficult and unreliable. Our study does not support the use of reamings for histology. An alternative technique should be used such as biopsy with the Harlow-Wood trephine.


The link between math anxiety and performance does not depend on working memory: A network analysis study.
Math anxiety (MA) and working memory (WM) influence math performance. Yet the interplay between them is not fully understood. Inconsistent results possibly stem from the multicomponent structure of math performance and WM. Using network analysis approach, we investigated the drivers of the MA, WM and math performance edges, and the contribution of each node to the network. First, 116 women completed a battery of tests and questionnaires. Second, we explored the generalizability of our model by applying it to a new data-set (Skagerlund et al., 2019; conceptual replication). The results revealed: (1) the links between MA and WM depend on specific task properties, specifically, WM tasks that require manipulation of numbers; (2) WM and MA are independently linked to math performance; and (3) each WM task is associated with different math abilities. The study provides a strong and reliable model showing the direct effects of math anxiety on math performance.


Deodorants: an experimental provocation study with hydroxycitronellal.
Axillary dermatitis is a common problem, particularly in individuals with contact allergy to fragrances. Many individuals suspect their deodorant to be the causal product of their fragrance allergy. It has been shown that deodorants containing cinnamic aldehyde (cinnamal) can elicit axillary dermatitis in patients sensitized to this substance. The aim of the present investigation was to evaluate the importance of hydroxycitronellal used in deodorants for the development of axillary dermatitis, when applied by individuals with and without contact allergy to this fragrance chemical. Patch tests with deodorants and ethanolic solutions containing hydroxycitronellal, as well as repeated open application tests (ROAT) with roll-on deodorants with and without hydroxycitronellal at different concentrations, were performed in 14 dermatitis patients, 7 with and 7 without contact allergy to hydroxycitronellal. A positive ROAT was noted only in the patients hypersensitive to hydroxycitronellal (P < 0.001) and only in the axilla to which the deodorants containing hydroxycitronellal had been applied (P < 0.001). Deodorants containing hydroxycitronellal in the concentration range of 0.032-0.32% used twice daily on healthy skin in individuals hypersensitive to hydroxycitronellal can elicit axillary dermatitis in a few weeks.


Evaluation of Risk Factors for Loss of Acceptable Alignment for Distal Radius Fractures That Are Nondisplaced or Minimally Displaced on Initial Presentation.
Numerous studies have evaluated risk factors for loss of acceptable radiographic alignment, as described by the American Academy of Orthopaedic Surgeons Clinical Practice Guidelines (CPG), following closed reduction of distal radius fractures (DRFs). Less is known about DRFs that are well aligned on initial presentation and do not require closed reduction. We evaluated the rate of and risk factors for displacement of DRFs that are nondisplaced or minimally displaced on initial presentation. This retrospective cohort study identified patients with nondisplaced or minimally displaced DRFs seen at a single academic tertiary center between 2015 and 2019. DRFs that required a reduction or initial surgical treatment based on the American Academy of Orthopaedic Surgeons CPG and those with a volar shear pattern were excluded. We recorded standard radiographic measurements on presentation and wrist radiographs after 6 weeks. Univariate and binary multivariable logistic regression analyses evaluated associations between sex, age, the presence of dorsal comminution, intra-articular involvement, associated ulnar fractures, and minimal displacement (vs nondisplacement on initial radiographs) with loss of acceptable alignment. Of the 110 included patients, 72% were female and the mean age was 52 years (SD, 17 years). Overall, 33 (30%) had displacement beyond the AAOS CPG criteria at 6 weeks. A multivariable analysis demonstrated that the presence of dorsal comminution (odds ratio, 37.8) and age >60 years (odds ratio, 3.6) were significantly associated with loss of acceptable alignment, whereas sex, intra-articular involvement, associated ulnar styloid/neck fractures, and minimal displacement were not associated. For DRFs that were initially nondisplaced or minimally displaced, the overall rate of unacceptable radiographic displacement at 6 weeks was 30%. Dorsal comminution and age >60 years were both independently associated with displacement, suggesting that patients with these risk factors may warrant closer follow-up than those without risk factors. Diagnostic IV.


[Factors Associated With Immediate Results of Coronary Artery Bypass Grafting in Patients With Ischemic Heart Disease in the Presence of Type 2 Diabetes].
to elucidate factors associated with cardiovascular events (CVE) after coronary artery bypass grafting (CABG) depending on the presence of type 2 diabetes mellitus (DM2). Medical records of 667 patients who underwent CABG during the period from 2006 to 2009 (317 patients with and 350 patients without DM2 and other disorders of glucose metabolism with comparable by sex, age and CABG characteristics) were analyzed retrospectively. The relationship of registered possible predictors with incidence of CVE was evaluated in a logistic regression model. Predictors of CVE after CABG were different depending on the presence of DM2. The presence of left ventricular aneurysm, mitral regurgitation, reduced left ventricular ejection fraction (LVEF) and elevated level of glycated hemoglobin were independent predictors of CVE in diabetic patients. The increase in the age of patients, on-pump CABG, combined operations, presence of mitral regurgitation, decrease in LVEF were predictors of CVE in non-diabetic patients. Predictors of CVE after CABG were different depending on the presence of DM2. Data obtained emphasize the importance of control of glycaemia in patients with DM2 for improvement of immediate results of CABG.


Biomechanical Analysis of Double-Level Oblique Lumbar Fusion with Different Types of Fixation: A Finite Element-Based Study.
One well-liked less invasive procedure is oblique lumbar interbody fusion (OLIF). The biomechanical characteristics of double-level oblique lumbar interbody fusion in conjunction with various internal fixations are poorly understood. The purpose of this study was to clarify the biomechanical characteristics of double-level oblique lumbar interbody fusion for osteoporosis spines using various internal fixation techniques. Based on CT scans of healthy male volunteers, a complete finite element model of osteoporosis in L1-S1 was established. After validation, L3-L5 was selected as the surgical segment to construct four surgical models: (a) two stand-alone cages (SA); (b) two cages with unilateral pedicle screws (UPS); (c) two cages with bilateral pedicle screws (BPS); and (d) two cages with bilateral cortical bone trajectory screws (CBT). Segmental range of motion (ROM), cage stress, and internal fixation stress were studied in all surgical models and compared with the intact osteoporosis model. The SA model had a minimal reduction in all motions. The CBT model had the most noticeable reduction in flexion and extension activities, while the reduction in the BPS model was slightly less than that in the CBT model but larger than that in the UPS model. The BPS model had the greatest limitation in left-right bending and rotation, which was greater than the UPS and CBT models. CBT had the smallest limitation in left-right rotation. The cage stress of the SA model was the highest. The cage stress in the BPS model was the lowest. Compared with the UPS model, the cage stress in the CBT model was larger in terms of flexion and LB and LR but slightly smaller in terms of RB and RR. In the extension, the cage stress in the CBT model is significantly smaller than in the UPS model. The CBT internal fixation was subjected to the highest stress of all motions. The BPS group had the lowest internal fixation stress in all motions. Supplemental internal fixation can improve segmental stability and lessen cage stress in double-level OLIF surgery. In limiting segmental mobility and lowering the stress of cage and internal fixation, BPS outperformed UPS and CBT.


Venous ulcer: clinical characteristics and risk factors.
Lower limb venous ulceration ranks among the 10 most common medical problems in Western countries and has significant socioeconomic impact. The aim of this study was to identify the risk factors for unhealed, recurrent, and large ulcers and to characterize patients with active or recently healed venous ulcers. We identified 97 patients and assessed 103 ulcerated limbs in 90 patients. All patients underwent clinical examination, arterial and venous system evaluation, ankle-brachial index determination, and ultrasound of the affected limb. Clinical characteristics included age, gender, race, ulcer duration, time since first episode, history of recurrence, localization of ulcer, ulcer area, eczema, ochre dermatitis, lipodermatosclerosis, pain, body mass index, and medical history data. Risk factors were identified by univariate analysis and estimated odds ratios. We assessed 90 patients (103 limbs) with active or healed venous leg ulcers, of whom 84.4% were Caucasian and 68.9% were female. Mean age was 56.0 ± 13.3 years. Ulcers had remained unhealed for <1 year in 40.7%. Lipodermatosclerosis, lower limb hyperpigmentation, edema, and eczema were seen in 96.7%, 95.6%, 94.4%, and 51.1% of patients, respectively. Pain was a frequent symptom in 74.4%. Body mass index was assessed in 85 patients: 30.6% were slightly, 36.5% moderately, and 7% severely obese. Patient age >60 years (odds ratio [OR] 4.0), extensive lipodermatosclerosis (OR 8.7), and previous history of ulceration (OR 19.9) were risk factors for unhealed ulcers. Time since first ulcer episode ≥ 2 years (OR 29.2) and incompetence of venous systems (OR 1.6) were risk factors for recurrence. Longstanding and large ulcers and recurrences are the main problems encountered by venous ulcer patients. Severe lipodermatosclerosis, previous ulcer history, and time since first ulcer episode ≥ 2 years are significant risk factors.


Role of CCAAT/enhancer-binding protein, histone acetylation, and coactivator recruitment in the regulation of malic enzyme transcription by thyroid hormone.
In chick embryo hepatocytes, activation of malic enzyme gene transcription by triiodothyronine (T3) is mediated by a T3 response unit (T3RU) that contains five T3 response elements (T3REs) plus five accessory elements that enhance T3 responsiveness conferred by the T3REs. Results from in vitro binding assays indicate that one of the accessory elements (region F) binds CCAAT/enhancer-binding protein-alpha (C/EBPalpha). Here, we investigated the role of C/EBPalpha in the regulation of malic enzyme transcription by T3. Transfection analyses demonstrated that the stimulation of T3RE function by region F did not require the presence of additional malic enzyme gene promoter sequences. Expression of a dominant negative C/EBP inhibited the ability of region F to stimulate T3 responsiveness. In chromatin immunoprecipitation assays, C/EBPalpha and TR associated with the malic enzyme T3RU in the absence and presence of T3 with the extent of the association being greater in the presence of T3. These observations indicate that C/EBPalpha interacts with TR on the malic enzyme T3RU to enhance T3 regulation of malic enzyme gene transcription. T3 treatment increased the acetylation of histones, decreased the recruitment of nuclear receptor corepressor and increased the recruitment of steroid receptor coactivator-1, CREB binding protein, and the thyroid hormone associated protein/mediator complex at the malic enzyme T3RU. In contrast, T3 treatment had no effect on the acetylation of histones and the recruitment of corepressors and coactivators at the T3RU that mediates the T3 activation of acetyl-CoA carboxylase-alpha gene transcription. We propose that differences between the malic enzyme T3RU and the ACCalpha T3RU in the ability of T3 to modulate histone acetylation and coregulatory protein recruitment are due to differences in the composition of the nuclear receptor complexes that bind these regulatory regions.


A chimeric human-mouse model of Sjögren's syndrome.
Despite recent advances in the understanding of Sjögren's Syndrome (SjS), the pathogenic mechanisms remain elusive and an ideal model for early drug discovery is not yet available. To establish a humanized mouse model of SjS, peripheral blood mononuclear cells (PBMCs) from healthy volunteers or patients with SjS were transferred into immunodeficient NOD-scid IL-2rγ(null) mouse recipients to produce chimeric mice. While no difference was observed in the distribution of cells, chimeric mice transferred with PBMCs from SjS patients produced enhanced cytokine levels, most significantly IFN-γ and IL-10. Histological examination revealed enhanced inflammatory responses in the lacrimal and salivary glands of SjS chimeras, as measured by digital image analysis and blinded histopathological scoring. Infiltrates were primarily CD4+, with minimal detection of CD8+ T-cells and B-cells. These results demonstrate a novel chimeric mouse model of human SjS that provides a unique in vivo environment to test experimental therapeutics and investigate T-cell disease pathology.