Tectorigenin protect HUVECs from H2O2-induced oxidative stress injury by regulating PI3K/Akt pathway.
Oxidative stress injury (OSI) occurs in many cardiovascular diseases, and the OSI of endothelial cells is the main pathological basis of these diseases. Tectorigenin has an effect on oxidative stress in fibroblasts, keratinocytes, and neuroblastoma. This study attempted to reveal the effect of Tectorigenin on OSI in endothelial cells. An OSI cell model was firstly established by treating human umbilical vein endothelial cells (HUVECs) with H2O2. The H2O2-induced HUVECs were further pre-treated with Tectorigenin or PI3K inhibitor. Then the viability and apoptosis of HUVECs were evaluated using MTT, Hochest 33258 staining and TUNEL staining. Lactate dehydrogenase (LDH) leakage, enzyme activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) level were measured through colorimetric assays. The expressions of apoptosis-related factors and the activation of the PI3K/Akt pathway in HUVECs were detected by RT-qPCR or Western blot. Tectorigenin had no inhibiting effect on the viability of HUVECs at the concentrations of 0.1, 0.5, 0.5, 1, and 10 μmol/L. Tectorigenin reversed the H2O2 induced-destruction of HUVECs morphology. Tectorigenin increased the viability and decreased the apoptosis of H2O2-induced HUVECs. Tectorigenin increased Bcl-2 expression and the enzyme activities of SOD and GSH-Px, but decreased LDH leakage, MDA level, and the expressions of Bax and Cleaved Caspase-3 in H2O2-induced HUVECs. Furthermore, Tectorigenin increased the ratios of p-PI3K to PI3K and p-Akt to Akt in H2O2-induced HUVECs. PI3K inhibitor had an opposite effect of Tectorigenin on the OSI in H2O2-induced HUVECs and its effect was further reversed by Tectorigenin. Tectorigenin protected HUVECs against H2O2-induced OSI via PI3K/Akt pathway.


Heavy metal poisoning: the effects of cadmium on the kidney.
The heavy metal cadmium (Cd) is known to be a widespread environmental contaminant and a potential toxin that may adversely affect human health. Exposure is largely via the respiratory or gastrointestinal tracts; important non-industrial sources of exposure are cigarette smoke and food (from contaminated soil and water). The kidney is the main organ affected by chronic Cd exposure and toxicity. Cd accumulates in the kidney as a result of its preferential uptake by receptor-mediated endocytosis of freely filtered and metallothionein bound Cd (Cd-MT) in the renal proximal tubule. Internalised Cd-MT is degraded in endosomes and lysosomes, releasing free Cd(2+) into the cytosol, where it can generate reactive oxygen species (ROS) and activate cell death pathways. An early and sensitive manifestation of chronic Cd renal toxicity, which can be useful in individual and population screening, is impaired reabsorption of low molecular weight proteins (LMWP) (also a receptor-mediated process in the proximal tubule) such as retinol binding protein (RBP). This so-called 'tubular proteinuria' is a good index of proximal tubular damage, but it is not usually detected by routine clinical dipstick testing for proteinuria. Continued and heavy Cd exposure can progress to the clinical renal Fanconi syndrome, and ultimately to renal failure. Environmental Cd exposure may be a significant contributory factor to the development of chronic kidney disease, especially in the presence of other co-morbidities such as diabetes or hypertension; therefore, the sources and environmental impact of Cd, and efforts to limit Cd exposure, justify more attention.


Effects of aging procedures on the topographic surface, structural stability, and mechanical strength of a ZrO2-based dental ceramic.
To determine the effects of different aging methods on the degradation and flexural strength of yttria-stabilized tetragonal zirconia (Y-TZP) METHODS: Sixty disc-shaped specimens (∅, 12mm; thickness, 1.6mm) of zirconia (Vita InCeram 2000 YZ Cubes, VITA Zahnfabrik) were prepared (ISO 6872) and randomly divided into five groups, according to the aging procedures (n=10): (C) control; (M) mechanical cycling (15,000,000 cycles/3.8Hz/200N); (T) thermal cycling (6,000 cycles/5-55°C/30s); (TM) thermomechanical cycling (1,200,000 cycles/3.8Hz/200N with temperature range from 5°C to 55°C for 60s each); (AUT) 12h in autoclave at 134°C/2bars; and (STO) storage in distilled water (37°C/400 days). After the aging procedures, the monoclinic phase percentages were evaluated by X-ray diffraction (XRD), and topographic surface analysis was performed by 3D profilometry. The specimens were then subjected to biaxial flexure testing (1mm/min, load 100kgf, in water). The biaxial flexural strength data (MPa) were analyzed by 1-way ANOVA and Tukey's test (α=0.05). The data for monoclinic phase percentage and profilometry (Ra) were analyzed by Kruskal-Wallis and Dunn's tests. ANOVA revealed that flexural strength was affected by the aging procedures (p=0.002). The M (781.6MPa) and TM (771.3MPa) groups presented lower values of flexural strength than did C (955MPa), AUT (955.8MPa), T (960.8MPa) and STO (910.4MPa). The monoclinic phase percentage was significantly higher only for STO (12.22%) and AUT (29.97%) when compared with that of the control group (Kruskal-Wallis test, p=0.004). In addition, the surface roughnesses were similar among the groups (p=0.165). Water storage for 400 days and autoclave aging procedures induced higher phase transformation from tetragonal to monoclinic; however, they did not affect the flexural strength of Y-TZP ceramic, which decreased only after mechanical and thermomechanical cycling.


Ligand and pathogen specificity of the Atlantic salmon serum C-type lectin.
An Atlantic salmon (Salmo salar) C-type lectin (SSL) binds to mannose and related sugars as well as to the surface of Aeromonas salmonicida. To characterize this lectin as a pathogen recognition receptor in salmon, aspects of its interaction with molecules and with intact pathogens were investigated. SSL was isolated using whole-yeast-affinity and mannan-affinity chromatography. The binding of SSL to the two major surface molecules of A. salmonicida, lipopolysaccharide (LPS) and A-layer protein was investigated by western blotting and enzyme-linked immunosorbent assays. Microbial binding specificity of SSL was examined by whole cell binding assays using a range of species. Carbohydrate ligand specificity of SSL was examined using glycan array analysis and frontal affinity chromatography. SSL showed binding to bacteria and yeast including, Pseudomonas fluorescens, A. salmonicida, A. hydrophila, Pichia pastoris, and Saccharomyces cerevisiae, but there was no detectable binding to Yersinia ruckeri. In antimicrobial assays, SSL showed no activity against Escherichia coli, Bacillus subtilis, S. cerevisiae, or A. salmonicida, but it was found to agglutinate E. coli. The major surface molecule of A. salmonicida recognized by SSL was shown to be LPS and not the A-layer protein. LPS binding was mannose-inhibitable. Glycans containing N-acetylglucosamine were shown to be predominant ligands. SSL has a distinct ligand preference while allowing recognition of a wide variety of related carbohydrate structures. SSL is likely to function as a wide-spectrum pattern recognition protein.


A single center retrospective study of paraneoplastic neurological syndromes with positive onconeural antibodies.
Paraneoplastic neurological syndromes (PNS) are rare immune-mediated disorders, and the detection of onconeural antibodies is helpful for PNS diagnosis. The aim of this study was to investigate the clinical characteristics of patients with PNS with positive onconeural antibodies in a single center in Hubei, China. We retrospectively analyzed the clinical characteristics of 54 patients with positive onconeural antibodies from January 2016 to September 2020. Among 780 patients with suspected PNS, 54 (6.9%) had positive onconeural antibodies. Of those 54 patients, 28 (51.8%) were diagnosed with definite PNS and 13 (24.1%) with possible PNS. Eighteen (33.3%) patients were confirmed with cancer. Ten PNS syndromes were detected among the 28 patients with definite PNS, and they had either classical (12/28, 42.8%) or non-classical syndromes (17/28, 60.7%). Peripheral neuropathy (9/28, 32.1%), subacute cerebellar degeneration (4/28, 14.3%), and limbic encephalitis (4/28, 14.3%) were the most common PNS syndromes. The anti-CV2/CRMP5-antibody was observed most frequently. Lung cancer was the most common tumor type. For patients with possible PNS, peripheral neuropathy was the most common PNS syndrome, and the anti-Tr-antibody was the most frequent onconeural antibody. Immunotherapy was effective in treating PNS. The anti-CV2/CRMP5-antibody was the most subsequently observed antibody. The manifestations of PNS are diverse and include peripheral neuropathy, subacute cerebellar degeneration, and limbic encephalitis. In patients with PNS, lung cancer was the most common tumor.


A technical improvement for crossed immunoelectrophoresis.
A simple antibody overlay technique for crossed immunoelectrophoresis is described. After the initial electrophoresis of antigens, the gel is overlaid with antibody-impregnated filter paper. This makes it necessary to pour only one gel, simplifying technique as compared with the conventional method.


Are average platelet volume, red cell distribution width and platelet distribution width guiding markers for acute appendicitis treatment options?
Acute appendicitis (AA) is the most common cause of surgery performed for the acute abdomen. The standard treatment for AA patients has been appendectomy for more than a century. The use of broad-spectrum antibiotics, the medical treatment option has come to the fore in the treatment of uncomplicated AA. Evaluate whether white blood cell (WBC), platelet count, mean platelet volume (MPV), platelet distribution width (PDW), red cell distribution width (RDW) and C-reactive protein (CRP) values of patients diagnosed with uncomplicated AA clinically, with laboratory tests and radiologically with abdominal computed tomography (CT) could be a marker for choosing medical or surgical treatment. 519 patients aged between 20 and 65 years who were diagnosed with uncomplicated AA by abdominal CT in our centre between January 2016 and January 2019 were retrospectively analysed. The presence of at least one of the criteria of 7 mm or more appendix diameter and oedema or fluid accumulation around the appendix was accepted as uncomplicated AA. After the diagnosis of AA, 223 patients were treated medically, while 296 patients underwent laparoscopic appendectomy. The first group included patients who were treated medically and the second group included patients who underwent laparoscopic appendectomy. Group 2 patients had higher mean platelet count (P < .005) and RDW (P = .003) values compared to Group 1 patients, while mean PDW (P < .001) values were lower compared to those of Group 1 patients. The differences between the mean WBC, CRP and MPV values of the groups were not statistically significant (P > .05). Recently, studies supporting antibiotic therapy have been conducted in patients diagnosed with AA. As a result, we think that PDW, RDW, and platelet values in patients diagnosed with uncomplicated AA may be a guide in choosing patients to be treated with surgery or antibiotics.


The synthesis of TiO2 and TiO2-Pt and their application in the removal of Cr (VI).
The deposition of noble metal on titanium dioxide (TiO2) has been considered as an effective strategy to improve the activity of TiO2. In this paper, TiO2 nanoparticles were prepared via a sol-gel route, followed by heat treatment at elevated temperatures. TiO2-Pt catalyst was prepared by deposition of platinum (Pt) on the surface of as-prepared TiO2 nanoparticles. TiO2 and TiO2-Pt were characterized by X-ray diffraction, transmission electron microscopy, Raman spectroscopy, ultraviolet-visible differential reflectance spectra and infrared spectroscopy. TiO2 and TiO2-Pt were used as heterogeneous catalysts for the removal of Cr (VI) under ultraviolet-light illumination. TiO2 prepared at low temperature had smaller particle size and higher specific surface area, and consequently had higher activity on the removal of Cr (VI). The Pt deposited on the surface of TiO2 favoured the separation of photo-produced electrons (e-) and holes (h+), inhibited the recombination of e- and h+, and enhanced Cr (VI) removal. However, its blocking of active sites also inhibited the removal of Cr (VI). The deposition of 1% (wt.%) Pt to TiO2 produced the optimum activity for the removal of Cr (VI). A lower pH favoured the adsorption of Cr (VI) on the surface of TiO2, and correspondingly enhanced the removal of Cr (VI).


Sponsorship of oncology clinical trials in the United States according to age of eligibility.
The sponsorship mix of trials relevant to young people with cancer has not been reported. Understanding this sponsorship mix may have implications for policies and regulations related to pediatric cancer drug development. We analyzed sponsorship of interventional trials first opened in the United States from 2007 to 2018 using the ClinicalTrials.gov registry. A total of 51 781 trials across non-oncology disciplines and 18 431 oncology trials were classified according to lower age of eligibility (≥18 years vs < 18 years). Studies were stratified according to sponsorship (industry vs non-industry). Trial characteristics were compared by sponsorship category. Trends in sponsorship were tracked over time. Within oncology trials for patients ≥ 18 years, sponsorship was 33% industry and 67% non-industry. Among oncology trials that included patients < 18 years, sponsorship was 16.6% industry and 83.4% non-industry (P < .001). 15.5% of industry-sponsored trials in non-oncology disciplines included patients < 18 years, whereas only 5.2% of industry-sponsored oncology trials were open to patients < 18 years (P < .001). Relative to trials with non-industry sponsors, there was a statistically significant increase in industry sponsorship of oncology trials that included patients < 18 years over time (P < .001). Trial characteristics differed significantly according to sponsor type regardless of age of eligibility. Interventional oncology trials that include patients < 18 years are less likely to be industry-sponsored compared to oncology trials exclusively in patients ≥ 18 years. Compared to other medical disciplines, a smaller proportion of industry-sponsored oncology trials included patients < 18 years. Trial sponsorship is associated with differential trial characteristics, such as trial duration and number of patients enrolled, regardless of age.


The Ties that Bind: Agnosia, Neglect and Selective Attention to Visual Scale.
Historical and contemporary treatments of visual agnosia and neglect regard these disorders as largely unrelated. It is thought that damage to different neural processes leads directly to one or the other condition, yet apperceptive variants of agnosia and object-centered variants of neglect share remarkably similar deficits in the quality of conscious experience. Here we argue for a closer association between "apperceptive" variants of visual agnosia and "object-centered" variants of visual neglect. We introduce a theoretical framework for understanding these conditions based on "scale attention", which refers to selecting boundary and surface information at different levels of the structural hierarchy in the visual array. We review work on visual agnosia, the cortical structures and cortico-cortical pathways that underlie visual perception, visuospatial neglect and object-centered neglect, and attention to scale. We highlight direct and indirect pathways involved in these disorders and in attention to scale. The direct pathway involves the posterior vertical segments of the superior longitudinal fasciculus that are positioned to link the established dorsal and ventral attentional centers in the parietal cortex with structures in the inferior occipitotemporal cortex associated with visual apperceptive agnosia. The connections in the right hemisphere appear to be more important for visual conscious experience, whereas those in the left hemisphere appear to be more strongly associated with the planning and execution of visually guided grasps directed at multi-part objects such as tools. In the latter case, semantic and functional information must drive the selection of the appropriate hand posture and grasp points on the object. This view is supported by studies of grasping in patients with agnosia and in patients with neglect that show that the selection of grasp points when picking up a tool involves both scale attention and semantic contributions from inferotemporal cortex. The indirect pathways, which include the inferior fronto-occipital and horizontal components of the superior longitudinal fasciculi, involve the frontal lobe, working memory and the "multiple demands" network, which can shape the content of visual awareness through the maintenance of goal- and task-based abstractions and their influence on scale attention. Recent studies of human cortico-cortical pathways necessitate revisions to long-standing theoretical views on visual perception, visually guided action and their integrations. We highlight findings from a broad sample of seemingly disparate areas of research to support the proposal that attention to scale is necessary for typical conscious visual experience and for goal-directed actions that depend on functional and semantic information. Furthermore, we suggest that vertical pathways between the parietal and occipitotemporal cortex, along with indirect pathways that involve the premotor and prefrontal cortex, facilitate the operations of scale attention.


Patterns of Vitamin D Levels and Exposures in Active and Inactive Noninfectious Uveitis Patients.
To compare serum vitamin D levels and patterns of ultraviolet light and dietary exposure among patients with active and inactive noninfectious uveitis and population controls. Prospective case-control study. All participants (n = 151) underwent serum 25-hydroxy vitamin D measurement and completed a questionnaire on vitamin D intake and ultraviolet light exposure. Serum 25-hydroxy vitamin D levels were compared between active and inactive uveitis groups and with local population estimates. Adult patients with active and inactive noninfectious uveitis were recruited from 2 Victorian tertiary hospitals and 1 private ophthalmic practice. Serum 25-hydroxy vitamin D levels were compared between patients with active and inactive uveitis and population-based estimates of serum 25-hydroxy vitamin D levels, stratified by geographic region and season. Vitamin D intakes and exposures based on questionnaire results, including vitamin D supplementation and sunlight exposures on weekdays and weekends, were compared between active and inactive uveitis groups. Serum vitamin D levels, intake of vitamin D, and exposure to sources of vitamin D. The median level of serum vitamin D in those with active uveitis (n = 74) was 46 nmol/l (interquartile range [IQR], 29-70 nmol/l), significantly lower than in the inactive control group (n = 77) at 64 nmol/l (IQR, 52-79 nmol/l; P < 0.001). The active uveitis group also showed lower median serum vitamin D levels than the local population median of 62 nmol/l (IQR, 46-77 nmol/l). Vitamin D supplementation also was associated significantly with uveitis inactivity (P = 0.026, Kendall's τ test). In a subanalysis of vitamin D-deficient participants, sun exposure was associated significantly with uveitis inactivity (P = 0.014 for weekday and weekend analyses). Participants with active uveitis showed significantly lower serum 25-hydroxy vitamin D levels than inactive uveitis patients and local population-based estimates. Vitamin D supplementation was found to be associated with decreased uveitis activity, as was sun exposure in those with vitamin D deficiency. These results suggest that vitamin D supplementation should be studied as an option for the prevention of uveitis relapse in at-risk patients.


Association Between Airborne Infection Isolation Room Utilization Rates and Healthcare Worker Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infections in 2 Academic Hospitals.
We compared healthcare worker severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates between March and August 2020 in 2 similar hospitals with high vs low airborne infection isolation room utilization rates but otherwise identical infection control policies. We found no difference in healthcare worker infection rates between the 2 hospitals, nor between patient-facing vs non-patient-facing providers.


Biomechanical factors influencing the beginning and development of osteoarthritis in the hip joint.
Osteoarthritis (OA) can be used as a common name for a group of overlapping pathological conditions when the balance between the processes of degradation and synthesis, in individual parts of the cartilage, is disturbed and leads to gradual cartilage destruction. A preventive approach toward OA helps with a timely diagnosis and subsequent treatment of this disease. One of the significant risk factors affecting development of hip joint OA is the mechanism and magnitude of mechanical loading on the joint. The main motivation for this work was to verify the hypothesis involving a pathologic cycle (overloading - change of locomotion - overloading) as contributory to the development of OA and whether it can be stopped, or at least partly decelerated, by a suitable change of movement stereotypes. Providing that there is a natural balance of muscular action, from the beginning of OA, the development of OA can be significantly decelerated. The return to a natural force balance can be achieved using suitable exercise and strengthening of muscular structures. In order to verify the hypothesis, we undertook experimental measurements of gait kinematics and a computational analysis of the hip joint using the Finite Element Method.


A reassessment of the activity of the third-generation cephalosporins against anaerobes and Staphylococcus aureus.
The in vitro activity of cefotaxime (CTX) alone and in combination with its metabolite desacetylcefotaxime (dCTX) was evaluated against 106 isolates of Bacteroides species. and 32 strains of Staphylococcus aureus. All strains were recovered from infected tissues of diabetic patients. Addition of dCTX to the parent compound markedly increased the inhibitory activity against Bacteroides species in general and Bacteroides fragilis and Bacteroides vulgatus in particular. No effect of the combination of both agents on Bacteroides thetaiotaomicron or Bacteroides ovatus was observed; 50% of B. fragilis infections were susceptible to CTX alone and 81% became susceptible to CTX plus dCTX. In addition, a partial synergistic interaction against 20 strains of B. fragilis resulted in a four- to nine-fold reduction in the minimal inhibitory concentration (MIC) after dCTX was added to CTX. Interestingly, 10 of 20 strains that exhibited an MIC of 64-128 micrograms/mL with CTX alone became very susceptible after the combination of parent and metabolite. This favorable positive interaction of both agents was also observed with S. aureus; a two- to four-fold reduction in MIC values was observed when dCTX was added.


Regulation of diacylglycerol kinase biosynthesis in Escherichia coli. A trans-acting dgkR mutation increases transcription of the structural gene.
The mechanism of a trans-acting mutation, dgkR1, which causes a 7-fold elevation of diacylglycerol kinase activity in membranes (Raetz, C. R. H., Kantor, G. D., Nishijima, M., and Jones, M. L. (1981) J. Biol. Chem. 256, 2109-2112) was investigated by direct measurement of diacylglycerol kinase polypeptide by high performance liquid chromatography and by construction of fusions of the dgkA promoter to beta-galactosidase and galactokinase. The dgkR1 mutation was demonstrated to act by increasing the transcription of the structural gene for diacylglycerol kinase, dgkA. Additionally, sn-glycerol-3-phosphate acyltransferase activities were shown to be decreased 30-50% in membranes from dgkR1 mutant strains. Increased diacylglycerol levels occurred when cells were grown on low osmolarity media. This did not affect dgkA expression. In a dgkR+ background, enhanced expression of sn-1,2-diacylglycerol kinase activity in cells containing a high copy number plasmid bearing dgkA decreased sn-1,2-diacylglycerol levels. However, overproduction of diacylglycerol kinase in a dgkR1 genetic background did not affect diacylglycerol levels, suggesting that the dgkR1 mutation affects diacylglycerol metabolism by mechanisms additional to enhancement of dgkA transcription.


Methionine sulfoximine in vivo modifies the tRNALys pool of developing rat brain.
tRNA was extracted from brains of 3-, 8-, and 18-day-old rats that were injected intracerebrally, 45 min before death, with [3H]methyl methionine or [8-3H]guanosine, and intraperitoneally, 3 h before death, with L-methionine-dl-sulfoximine (MSO), a methylation-activating convulsant agent. Although there was no effect of age or of MSO on the per gram yield of tRNA, its specific radioactivity (dpm/A260) was highest at 3 days in both the control and the MSO groups. Age- and MSO-related changes in tRNALys content of the brain tRNA pool were investigated by means of benzoylated DEAE-cellulose (BDC) and reverse-phase chromatography (RPC). BDC chromatography revealed tRNALys species in the brains of the MSO-treated animals that were absent in control brains. Of particular interest was the finding that differences in RPC-5 chromatographic mobility between control and MSO-tRNALys species were abolished by conversion of lysyl-tRNA, suggesting that the MSO-elicited change(s) in tRNALys structure involved the binding site(s) for lysine. Two additional findings were made: (a) lysine acceptance by the [3H]methyl-labeled tRNALys purified from brains of the MSO-treated animals was higher than that of controls at 18 days; and (b) omission of the BDC chromatographic step accentuated the differences in mobility on RPC-5 columns between tRNALys species of control and MSO-treated animals. Lastly, we found that some tRNALys species of control and MSO-treated brains contained significantly different proportions of N2-methyl guanine and 1-methyl adenine, relative to controls. These MSO-elicited changes in the methyl base content of tRNALys of immature rat brain are the first evidence of an alteration of brain tRNA structure by a centrally acting excitatory agent.


Centrohelid heliozoans of Ukraine with a description of a new genus and species (Haptista: Centroplasthelida).
New data on the species diversity and morphology of centrohelid heliozoans in freshwater, marine, and soil habitats of Ukraine were obtained. Cell coverings (scales and spicules) were observed using scanning and transmission electron microscopy. Eighteen species from seven genera of centrohelids and unidentifiable Heterophrys-like organisms were revealed. The micrographs and detailed morphological descriptions of observed species and their comparison with previously found centrohelids are provided. A new genus and three new species Acanthocystis tyrasiana sp. nov., Pterocystis borysthenica sp. nov., and Khitsovia mutabilis gen. et sp. nov. were described. Molecular phylogenetic analyses based on 18S rRNA sequences, obtained for three strains, expand our knowledge on the diversity and evolution of centrohelids within the Pterista clade. The novel data on the morphology of studied scales supplement available information on the intraspecific variability of centrohelid heliozoans.


A cross-sectional study of the perceived stressfulness of several life events.
Adults from different age groups (18-24, 30-40, and 65-86) were tested to determine if they differ in their perception of certain stressful life events. Twenty adults from each age group were asked to rate a series of events according to their perceived relative stressfulness; included were events thought to be particularly salient for elderly adults. Amster and Krauss' list of events and Holmes and Rahe's procedure for quantifying stress were used. Group differences were not found for the elderly salient events; however it was found that elderly adults perceive death-related events as less stressful than do younger adults.


The carboxy-terminal domain of ROS1 is essential for 5-methylcytosine DNA glycosylase activity.
Arabidopsis thaliana repressor of silencing 1 (ROS1) is a multi-domain bifunctional DNA glycosylase/lyase, which excises 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) as well as thymine and 5-hydroxymethyluracil (i.e., the deamination products of 5mC and 5hmC) when paired with a guanine, leaving an apyrimidinic (AP) site that is subsequently incised by the lyase activity. ROS1 is slow in base excision and fast in AP lyase activity, indicating that the recognition of pyrimidine modifications might be a rate-limiting step. In the C-terminal half, the enzyme harbors a helix-hairpin-helix DNA glycosylase domain followed by a unique C-terminal domain. We show that the isolated glycosylase domain is inactive for base excision but retains partial AP lyase activity. Addition of the C-terminal domain restores the base excision activity and increases the AP lyase activity as well. Furthermore, the two domains remain tightly associated and can be co-purified by chromatography. We suggest that the C-terminal domain of ROS1 is indispensable for the 5mC DNA glycosylase activity of ROS1.


Novel bimetallic MOF derived hierarchical Co@C composites modified with carbon nanotubes and its excellent electromagnetic wave absorption properties.
In the severe electromagnetic wave pollution situation, the absorbers must meet the requirements of lightweight, strong absorption, thin thickness and wide band. Under such a circumstance, it is of great significance to construct reasonable structure and composition for excellent electromagnetic wave absorption. Therefore, the Co/C composites anchored with carbon nanotubes (Co@CNTs) have been successfully prepared by rationally regulating the growth of bimetallic MOF and subsequent pyrolysis process. It is revealed that the conduction loss and polarization loss caused by the carbon nanotubes with different lengths and densities and the porosity of the composites are together responsible for the attenuation of electromagnetic wave. As expected, the hierarchical Co@CNTs composites showed a strong reflection loss of -76.6 dB and a broad effective absorption bandwidth of 6.2 GHz through the improvement of impedance matching and electromagnetic wave absorption ability. Herein, this work presents a strategy for the development of composites as promising electromagnetic wave absorbent.


Early results of bare metal extension stent for thoracoabdominal aortic dissection.
Debakey type I and IIIb aortic dissections are complicated by extension along the full length of the aorta. Over the long term, the thoracoabdominal aorta in these patients often continues to degenerate, requiring endovascular or open repair. The purpose of this investigation is to determine the early clinical outcome on aortic remodeling using a composite thoracic stent graft and thoracoabdominal bare metal extension stenting strategy. From April 2019 to April 2021, 73 patients with Debakey I/IIIb aortic dissection underwent endovascular stent graft repair of the descending thoracic aorta and repair of the thoracoabdominal aorta using bare metal extension stenting. Preoperative and follow-up surveillance computed tomography imaging scans were analyzed. Fifty-three (73%) patients had a Debakey I aortic dissection, and 50 (69%) patients underwent surgery during the chronic (time to surgery >30 days) dissection phase. Mortality at 30 days was 4% (3 hyperacute patients). Stroke occurred in 3 (4%), paraparesis in 2 (2.7%), and acute renal failure requiring dialysis occurred in 2 (2.7%) patients. On postoperative and follow-up computed tomography, there was a significant increase in false lumen thrombosis (P < .001). This coincided with a significant increase in true lumen fraction suggestive of positive aortic remodeling (P < .001) at the time of latest follow-up. Altering the course of aortic remodeling, with placement of a dissection stent in the thoracoabdominal aorta simultaneous with descending thoracic aortic repair may promote true lumen re-expansion and false lumen thrombosis during acute and chronic dissection phases.


Use of [32P]RNA probes for the dot-hybridization detection of potato spindle tuber viroid.
A dot-hybridization assay using 32P-labelled RNA probes (+RNA and cRNA) transcribed from potato spindle tuber viroid (PSTV) cDNA was described. A complete cDNA copy of PSTV, originally cloned in pBR 322 (pAV 401) was subcloned in the BamHI site of a 'Riboprobe' cloning vectors pSP 64 and pSP 65 in opposite orientations. The reconstructed plasmids were designated pDX 1 and pDX 4, respectively. Transcription of pDX 1 and pDX 4 plasmids by SP6 RNA polymerase resulted in the generation of PSTV-specific RNA (+RNA) and PSTV complementary RNA (cRNA), respectively. The cRNA probe was much more sensitive than the +RNA probe and the nick-translated cDNA probe from the plasmid pAV 401 for the detection of PSTV in clarified plant sap. As little as 1.4 pg of purified PSTV mixed in clarified sap from uninoculated tomato leaves has been detected using cRNA probe. A relatively simple procedure using cetyltrimethyl ammonium bromide (CTAB) as nucleic acid precipitant and an enrichment step for the purification of PSTV was described.


Gestational age and fetal growth in relation to maternal ovarian cancer risk in a Swedish cohort.
Pregnancy influences subsequent maternal ovarian cancer risk. To date, there is limited evidence whether two characteristics of pregnancy, gestational age and birth weight, could modify risk. We studied 1.1 million Swedish women who delivered singleton births between 1973 and 2001. Information on infant gestational age and birth weight was abstracted from the nationwide Swedish Birth Register. Women were followed prospectively through linkage with other population-based registers for occurrence of ovarian cancer, death, or emigration through 2001. Hazard ratios [relative risk (RR), 95% confidence interval (95% CI)] from Cox models were used to estimate associations between gestational age, birth weight, and epithelial ovarian cancer risk. During 12.6 million person-years, 1,017 epithelial ovarian cancers occurred. Mean age at diagnosis was 43 years. Compared with women with term deliveries (>/=40 weeks), women with moderately (35-36 weeks) or very (<35 weeks) preterm deliveries had increased risks of epithelial ovarian cancer (RR 1.4, 95% CI 1.0-2.0 and RR 2.3, 95% CI 1.3-3.8, respectively). In contrast, women giving birth to small-for-gestational-age babies had a reduced risk (RR 0.7, 95% CI 0.4-1.0). Stratifying on birth weight and gestational age, there was a strong protective effect of low birth weight on maternal risk of epithelial ovarian cancer among term deliveries, whereas birth weight seemed to have little effect among preterm births (P(interaction) = 0.022). Our results lend further support that the hormonal milieu of a pregnancy may modify long-term risk of developing ovarian cancer. 32).


Role of macrophage-derived factors in generation of cytotoxic and antibody responses.
The ability of macrophage subpopulations, separated by virtue of differences in size, to liberate soluble factors able to reconstitute antibody and cell-mediated immune responses in macrophage-depleted lymphoid cultures has been investigated. Evidence is presented to show that all macrophages release trypsin- and pepsin-sensitive molecules with molecular weights of 30,000 to 35,000 and 50,000 to 70,000 that are able to reconstitute only syngeneic lymphocyte responses. In contrast, a molecule(s) with molecular weight of 10,000 to 15,000 daltons is released only by large macrophages and can apparently reconstitute both syngeneic and allogeneic lymphocyte responses. This material is also pepsin-sensitive and, to a lesser degree, trypsin-sensitive.


Rehabilitation Training Following Retroperitoneal Haemorrhage: A Case Report and Review of the Literature.
We report a case of a Chinese man who developed retroperitoneal haemorrhage almost 1 year after surgery for pelvic fracture (1). To the best of our knowledge, this type of delayed haemorrhaging is rarely observed in clinical practice. We also review the literature to identify the common causes of retroperitoneal haemorrhage in patients undergoing surgery for pelvic fracture and to examine the aetiology of this case.


Superresolution in color videos acquired through turbulent media.
Color videos acquired with a single CCD through turbulent media can be enhanced in their resolution beyond the limit defined by the image sampling rate. We provide a mathematical justification for this claim, present an efficient superresolution algorithm and its experimental verification on a real-life video, and finally, discuss its potentials and limitations.


Apolipoprotein CIII overexpressing mice are predisposed to diet-induced hepatic steatosis and hepatic insulin resistance.
Nonalcoholic fatty liver disease (NAFLD) and insulin resistance have recently been found to be associated with increased plasma concentrations of apolipoprotein CIII (APOC3) in humans carrying single nucleotide polymorphisms within the insulin response element of the APOC3 gene. To examine whether increased expression of APOC3 would predispose mice to NAFLD and hepatic insulin resistance, human APOC3 overexpressing (ApoC3Tg) mice were metabolically phenotyped following either a regular chow or high-fat diet (HFD). After HFD feeding, ApoC3Tg mice had increased hepatic triglyceride accumulation, which was associated with cellular ballooning and inflammatory changes. ApoC3Tg mice also manifested severe hepatic insulin resistance assessed by a hyperinsulinemic-euglycemic clamp, which could mostly be attributed to increased hepatic diacylglycerol content, protein kinase C-ϵ activation, and decreased insulin-stimulated Akt2 activity. Increased hepatic triglyceride content in the HFD-fed ApoC3Tg mice could be attributed to a ≈ 70% increase in hepatic triglyceride uptake and ≈ 50% reduction hepatic triglyceride secretion. These data demonstrate that increase plasma APOC3 concentrations predispose mice to diet-induced NAFLD and hepatic insulin resistance.


Prognostic Factor Risk Groups for Clinical Stage I Seminoma: An Individual Patient Data Analysis by the European Association of Urology Testicular Cancer Guidelines Panel and Guidelines Office.
The relapse rate in patients with clinical stage I (CSI) seminomatous germ cell tumor of the testis (SGCTT) who were undergoing surveillance after radical orchidectomy is 4-30%, depending on tumor size and rete testis invasion (RTI). However, the level of evidence supporting the use of both risk factors in clinical decision-making is low. We aimed to identify the most important prognostic factors for relapse in CSI SGCTT patients. Individual patient data for 1016 CSI SGCTT patients diagnosed between 1994 and 2019 with normal postorchidectomy serum tumor marker levels and undergoing surveillance were collected from nine institutions. Multivariable Cox proportional hazard regression models were fit to identify the most important prognostic factors. The primary endpoint was the time to first relapse by imaging and/or markers. Relapse probabilities were estimated by the Kaplan-Meier method. After a median follow-up of 7.7 yr, 149 (14.7%) patients had relapsed. Categorical tumor size (≤2, >2-5, and >5 cm), presence of RTI, and lymphovascular invasion were used to form three risk groups: low (56.4%), intermediate (41.3%), and high (2.3%) risks with 5-yr cumulative relapse probabilities of 8%, 20%, and 44%, respectively. The model outperformed the currently used model with tumor size ≤4 versus >4 cm and presence of RTI (Harrell's C index 0.65 vs 0.61). The low- and intermediate-risk groups were validated successfully in an independent cohort of 285 patients. The risk of relapse after radical orchidectomy in CSI SGCTT patients under surveillance is low. We propose a new risk stratification model that outperformed the current model and identified a small subgroup with a high risk of relapse. The risk of relapse after radical orchidectomy in patients with clinical stage I seminomatous germ cell tumor of the testis is low. We propose a new risk stratification model that outperformed the current model and identified a small subgroup with a high risk of relapse.


Radiographic findings in children with psychosocial dwarfism.
The diagnosis of psychosocial dwarfism is established through history, the determination of delay in growth and skeletal maturation, the lack of evidence of organic disease and accelerated growth and psychomotor development in a nuturing environment. Radiographically temporary widening of the cranial sutures may be detected in a follow up examination or less often already at the time of initial examination. Determination of wide cranial sutures may be contributary in establishing the diagnosis of psychosocial dwarfism. In a patient with this syndrome and lack of neurological signs or symptoms widening of the cranial sutures is an expected finding and no further neuroradiologic studies are necessary.


[The impact of educational level on cognitive assessments in young patients admitted to rehabilitation after ischaemic stroke].
We propose to assess the impact of educational level on cognitive tests at admission and discharge after a period of cognitive rehabilitation in young patients after ischaemic stroke. We considered secondary and higher education (group A) and less than 6 years of formal education (group B). We compared A and B using χ2 and Kruskal-Wallis. We studied A and B as predictors of verbal and working memory at discharge. Verbal and working memories were assessed at admission and discharge using Rey Auditory Verbal Learning Test (RAVLT) and DIGITS of the Barcelona Test respectively. We analysed n=277 patients (55% belonging to A, mean age of 51 years) admitted to a specialised centre in Spain between 2009 and 2019. We found significant differences (P<.05) at admission, all in favour of A in the assessments of attention, inhibition, visuoperception, visuoconstruction, verbal fluency and comprehension. In DIGITS and RAVLT-learning we found differences at admission. In Digits and RAVLT-recognition we found differences at discharge, all in favour of A. We found no differences in age, severity, time at admission, or length of stay in hospital. Nor did we find differences in cognitive gains or treatment efficiency in memory tests. The groups A and B did not predict RAVLT (R2=.53) or DIGITS (R2=.48). A scores better in 63% of tests at admission and in 75% of tests at discharge, A and B are similar in gains and efficiency on memory tests.


NMR study of the cataract-linked P23T mutant of human gammaD-crystallin shows minor changes in hydrophobic patches that reflect its retrograde solubility.
The Pro23 to Thr (P23T) mutation in human gammaD-crystallin (HGD) shows several cataract phenotypes. We found earlier [A. Pande, O. Annunziata, N. Asherie, O. Ogun, G.B. Benedek, J. Pande, Decrease in protein solubility and cataract formation caused by the Pro23 to Thr mutation in human gamma D-crystallin, Biochemistry 44 (2005) 2491-2500] that the mutation dramatically lowers the solubility of P23T but the overall protein fold is maintained. Recently we observed that solutions of P23T showed liquid-liquid phase transition behavior similar to that of HGD but the liquid-protein crystal phase transition was altered, suggesting an asymmetric distribution of "sticky" patches on the protein surface [J.J. McManus, A. Lomakin, O. Ogun, A. Pande, M. Basan, J. Pande, G.B. Benedek, Altered phase diagram due to a single point mutation in human gammaD-crystallin, Proc. Natl. Acad. Sci. USA 104 (2007) 16856-16861]. Here we present high-resolution NMR studies of HGD and P23T in which we have made nearly complete backbone assignments. The data provide a structural basis for explaining the retrograde solubility of P23T by (a) identifying possible "sticky" patches on the surface of P23T and (b) highlighting their asymmetric distribution.


Comparison of Police Data on Animal Cruelty and the Perception of Animal Welfare NGOs in Hungary.
Animal cruelty has been a criminal offence in Hungary since 2004 and the legislator has tightened and differentiated the regulations in several waves since then. However, it is not an exaggeration to say that the public is often impatient and dissatisfied with the actions of the authorities in relation to animal cruelty. In our research, based on the data of the Criminal Investigation Department of the National Police Headquarters, we examined the opinions of 99 out of a total of 155 police stations in Hungary whose staff currently working there had experience in dealing with animal cruelty. The investigators gave their opinion on a total of 1169 cases in which some kind of police action was taken, either following a report to the police or as a result of their own investigative actions. In another survey, we questioned those members of society who are most committed to animal protection using a self-completion questionnaire. The questionnaire sent to the 116 Hungarian animal welfare non-governmental organisations (NGOs) on the publicly available lists was also posted for a short period on the social networking site of NGO activists. Among those who responded, a total of 150 identified as active participants in the animal protection work of these NGOs. The picture of the police treatment of animal cruelty, as perceived by NGOs working in the field of animal protection, is significantly less favourable than suggested by the police data. According to the official data, 77.7% of reports initiated an investigation, while the vast majority of animal welfare activists (81.3%) suspects that only 25% of the reports result in action by the prosecuting authority.


Lentiviral-mediated targeted transgene expression in dorsal spinal cord glia: tool for the study of glial cell implication in mechanisms underlying chronic pain development.
Activated glial cells in the dorsal spinal cord take an important part in the development of pain after peripheral nerve injury. Our understanding of mechanisms involved in functional changes of spinal glia remains incomplete. Excepting drugs that completely disrupt glial function, pharmacological studies fail to target glia and to modify locally its function in order to really discriminate the role of neuronal versus glial cells in chronic pain. We developed an intraspinal gene transfer approach using pseudotyped lentiviral-derived vector targeting highly preferentially glial cells. Single microinjection of vector expressing EGFP under a CMV promoter control (LV-EGFP) allowed vector diffusion along a rostro-caudal axis but strictly restricted to the grey matter of the ipsilateral dorsal spinal cord. EGFP transgene was mainly expressed in astrocytes and microglial cells whereas less than 9% of cells containing EGFP were neurons. Notably, LV-EGFP administration and EGFP overexpression in glial cells did neither modify glial activity, nor alter animal's nociceptive or locomotor behaviors. Targeted modulation of the expression of gene of interest in glial cells, closely restricted to a particular region of the spinal cord, may thus represent an interesting approach to refine the understanding of mechanisms by which spinal glial cells participate in pain processing.


Wavelength selection method with standard deviation: application to pulse oximetry.
Near-infrared spectroscopy provides useful biological information after the radiation has penetrated through the tissue, within the therapeutic window. One of the significant shortcomings of the current applications of spectroscopic techniques to a live subject is that the subject may be uncooperative and the sample undergoes significant temporal variations, due to his health status that, from radiometric point of view, introduce measurement noise. We describe a novel wavelength selection method for monitoring, based on a standard deviation map, that allows low-noise sensitivity. It may be used with spectral transillumination, transmission, or reflection signals, including those corrupted by noise and unavoidable temporal effects. We apply it to the selection of two wavelengths for the case of pulse oximetry. Using spectroscopic data, we generate a map of standard deviation that we propose as a figure-of-merit in the presence of the noise introduced by the living subject. Even in the presence of diverse sources of noise, we identify four wavelength domains with standard deviation, minimally sensitive to temporal noise, and two wavelengths domains with low sensitivity to temporal noise.


Sketching neoteric solvents for boosting drugs bioavailability.
Emerging neoteric solvents are being the subject of growing attention due to their lower cost and environmental impact, so they are being applied in a broad spectrum of industries. Among them, the pharmaceutical sector is demanding new environmentally friendly and non-toxic solvents able to enhance drugs solubility and stability. The introduction of ionic liquids turned out to be a breakthrough in the field of Green Chemistry opening up new separation and catalysis opportunities. In this sense, the options represented by Deep Eutectic Solvents make up an attractive alternative due to the low cost of their raw material, simple synthesis, and eco-friendly character. In line with these findings, Therapeutic Deep Eutectic Solvents and Natural Deep Eutectic Solvents are new and promising alternatives to improve the bioavailability of drugs in pharmaceutical formulations. This leading article is focused on providing a general picture of the advantages and drawbacks of these new solvents as well as the main research lines and perspectives to achieve efficient drugs delivery systems.


Independent Association of Obesity and Nonroutine Discharge Disposition After Elective Anterior Cervical Discectomy and Fusion for Cervical Spondylotic Myelopathy.
The prevalence of obesity continues to rise in the United States at a disparaging rate. Although previous studies have attempted to identify the influence obesity has on short-term outcomes following elective spine surgery, few studies have assessed the impact on discharge disposition following anterior cervical discectomy and fusion (ACDF) for cervical spondylotic myelopathy (CSM). The aim of this study was to determine whether obesity impacts the hospital management, cost, and discharge disposition after elective ACDF for adult CSM. The National Inpatient Sample database was queried using the International Classification of Diseases, 10th revision, Clinical Modification, coding system to identify all (≥18 years) patients with a primary diagnosis of CSM undergoing an elective ACDF for the years 2016 and 2017. Discharge weights were used to estimate national demographics, Elixhauser comorbidities, complications, length of stay, total cost of admission, and discharge disposition. There were 17,385 patients included in the study, of whom 3035 (17.4%) had obesity (no obesity: 14,350; obesity: 3035). The cohort with obesity had a significantly greater proportion of patients with 3 or more comorbidities compared with the cohort with no obesity (no obesity: 28.1% vs. obesity: 43.5%, P < 0.001). The overall complication rates were greater in the cohort with obesity (no obesity: 10.3% vs. obesity: 14.3%, P = 0.003). On average, the cohort with obesity incurred a total cost of admission $1154 greater than the cost of the cohort with no obesity (no obesity: $19,732 ± 11,605 vs. obesity: $20,886 ± 10,883, P = 0.034) and a significantly greater proportion of nonroutine discharges (no obesity: 16.6% vs. obesity: 24.2%, P < 0.001). In multivariate regression analysis, obesity, age, race, health care coverage, hospital bed size, region, comorbidity, and complication rates all were independently associated with nonroutine discharge disposition. Our study demonstrates that obesity is an independent predictor for nonroutine discharge disposition following elective anterior cervical discectomy and fusion for cervical spondylotic myelopathy.


Structure and stability of warfarin-sodium inclusion complexes formed with permethylated monoamino-β-cyclodextrin.
Inclusion complexes of warfarin enantiomers with permethylated monoamino-β-cyclodextrin (PMMABCD) were characterized using CE and (1)H NMR spectroscopy in aqueous solution. These techniques gave complementary information on the stability and the structure of the diastereomeric host-guest inclusion complexes. The stability constants were determined from CE experiments in a wide pH range. Change in the migration order on the variation of the pH was observed. (1)H NMR assignments have been established for the seven non-equivalent carbohydrate units of the host in the complex at pH 7-9. Specific H-H distance restraints were obtained from NOESY experiments and were introduced into molecular modeling to establish the geometry of the inclusion complexes. It was found that the open side chain warfarin enters the cavity from the primary side of the CD. The orientation of the coumarin ring within the cavity has the same preference for the two warfarin enantiomers owing to an ionic interaction with the amino group of the CD. Accordingly, enantioselectivity at pH 8.5 arises from the difference in the CH/π interactions between warfarin aromatics and the manifold of CH groups of the CD.


Ethnopharmacology, phytochemistry, and bioactivities of Hieracium L. and Pilosella Hill (Cichorieae, Asteraceae) species.
Species of the genera Hieracium and Pilosella have been used in folk medicine for centuries in many parts of the world. The most wiedly used species is P. officinarum Vaill., included in the British and French Pharmacopoeias and sold as part of different commercial products. This review critically appraises the state-of-art of ethnopharmacology, specialised metabolites, bioactivities, and toxicity of members of Hieracium and Pilosella. Thus, gaps in scientific knowledge can be identified, also focusing on the development of products with pharmacological applications. Literature data of Hieracium and Pilosella species were mainly retrieved using different electronic databases such as Web of Science, Google Scholar, SciFinder, and PubMed. Other electronic resources included worldwide databases on ethnobotany, ethnopharmacology, and phytochemistry as well as government reports. Additionally, ancient texts and local information such as PhD and MSc theses, and books were consulted. A comprehensive analysis of the above mentioned sources revealed that only 34 out of the about 850 described species within the genera Hieracium and Pilosella have been reported in the context of traditional medicinal and ethnobotanical knowledge. The most often mentioned species is P. officinarum which has been widely used due to its diuretic effects. Other popular uses of Hieracium and Pilosella species include the treatment of skin, gastric, and intestinal diseases as well as respiratory and vascular ailments. Moreover, taxa of the two genera have been used as antiobiotics, antiseptics, antidiabetics, tonics, antiepileptics, antiphlogistics, emetics, wound healing drugs, astringents, haemostatics, and detoxificants. Finally, uses as a wild vegetable, fodder, plant for hunting and for charming rituals have also been mentioned. Phytochemical research revealed a richness in phenolic compounds and flavonoids. Moreover, coumarins, sesquiterpene lactones, terpenoids, and phytosterols were found in Hieracium and Pilosella. Experimental research conducted to support traditional uses mainly include in vitro tests, while assays based on in vivo models (including humans) are rather limited. Also, the vast majority of the studies did not identify the compounds responsible for the detected bioactivities. These established bioactivities include antidiabetic, anti-inflammatory, antibacterial, antimycotic, antiviral, cytotoxic and antiproliferative, diuretic, gastroprotective, antiepileptic, hypotensive, anti-obesity, arthropodicidal, and skin rejuvenating activities. Finally, limited toxicity studies have been conducted on members of Hieracium and Pilosella. Taxa belonging to Hieracium and Pilosella have been confirmed to exert diuretic, anti-inflammatory, and antimicrobial effects, which is in line with their long traditional use. Moreover, the above mentioned fields of application hint to the most promising routes for the development of new marketable products. Nonetheless, additional data from an in-depth research on bio-active specialised metabolites such as sesquiterpenoids, sesquiterpene lactones, and coumarines, their bioactivities and toxicity, and their biosynthesis are still warranted.


FP-ADMET: a compendium of fingerprint-based ADMET prediction models.
The absorption, distribution, metabolism, excretion, and toxicity (ADMET) of drugs plays a key role in determining which among the potential candidates are to be prioritized. In silico approaches based on machine learning methods are becoming increasing popular, but are nonetheless limited by the availability of data. With a view to making both data and models available to the scientific community, we have developed FPADMET which is a repository of molecular fingerprint-based predictive models for ADMET properties. In this article, we have examined the efficacy of fingerprint-based machine learning models for a large number of ADMET-related properties. The predictive ability of a set of 20 different binary fingerprints (based on substructure keys, atom pairs, local path environments, as well as custom fingerprints such as all-shortest paths) for over 50 ADMET and ADMET-related endpoints have been evaluated as part of the study. We find that for a majority of the properties, fingerprint-based random forest models yield comparable or better performance compared with traditional 2D/3D molecular descriptors. The models are made available as part of open access software that can be downloaded from https://gitlab.com/vishsoft/fpadmet .


IgG1 and IgG4 serum antibody responses in asymptomatic and clinically expressed cystic echinococcosis patients.
IgG1 and IgG4 subclass antibody responses were investigated in two clinically different groups of hepatic cystic echinococcosis (CE) patients. One group consisted of surgically proven CE cases (clinically expressed hospitalized cases) and a second group comprised asymptomatic CE patients (first time community detected cases) diagnosed by portable ultrasound and serology in four different endemic communities. Fifty eight sera from surgically proven CE patients and 133 sera from asymptomatic ultrasound diagnosed CE cases were screened by ELISA using purified human hydatid cyst fluid antigen B for total specific IgG, IgG1 and IgG4 antibodies. Fifty sera from healthy individuals from within endemic regions were used as control negatives. Compared to control negatives total IgG antibody levels were elevated in both surgically proven (85%) and asymptomatic CE cases (77%) but there was no significant difference between the two groups. IgG1 subclass antibody levels were also elevated in both surgically proven (55%) and asymptomatic cases (58%) compared to endemic controls and similarly the difference in this response was not significant between these two groups. In contrast the prevalence of IgG4 antibodies in surgically confirmed chronic CE patients was greater (71%) than the respective IgG1 antibody levels (55%). The greatest difference in specific antibody response, between advanced surgically confirmed CE patients and ultrasound detected asymptomatic CE cases, was observed for IgG4 antibody levels which were detected in 71% of symptomatic compared to only 23% of asymptomatic patients (P < 0.0001). These observations confirm that IgG4 is an important diagnostic parameter for clinically expressed cystic echinococcosis in humans and suggest that a switch from a predominant IgG1 response to IgG4 might occur in CE patients as the disease progresses.


Eicosapentaenoic acid reduces the pulmonary vein arrhythmias through nitric oxide.
Omega-3 polyunsaturated fatty acids can modulate cardiac electrophysiology and reduce the genesis of atrial fibrillation. This study investigates the potential mechanisms through which eicosapentaenoic acid (EPA) reduces pulmonary vein (PV) arrhythmogenesis. Conventional microelectrodes were used to record the action potentials (APs), before and after the EPA (0.1 μM and 1.0 μM) administration with and without the presence of a nitric oxide (NO) synthase inhibitor (L-NAME, 100 μM) in isolated rabbit PV tissue preparations. Furthermore, indo-1 fluorimetric ratio technique was used to evaluate intracellular calcium in isolated single PV cardiomyocytes with or without incubation of EPA (1.0 μM, 30 min). EPA concentration-dependently reduced the PV spontaneous beating rate (P<0.05). EPA (1.0 μM) also reduced the amplitude of delayed afterdepolarizations (P<0.05). EPA hyperpolarized the maximal diastolic potential (MDP), shortened AP duration, increased AP amplitude (APA), and reduced diastolic tension and contractility. However, EPA in the presence of L-NAME or omega-9 fatty acids (oleic acid, 1.0 μM) did not have any effect on PV spontaneous activity, AP morphology, or contractile force. A linear regression shows that the decrease in PV spontaneous beating rates induced by EPA correlated well with the changes of MDP, APA, diastolic tension, and contractile force of PVs. In addition, intracellular Ca(2+) transient and sarcoplasmic reticulum Ca(2+) content were significantly more decreased in the EPA-treated cardiomyocytes than in control PV cardiomyocytes as observed by indo-1 fluorescence. EPA reduces PV arrhythmogenesis through the mechanoelectrical feedback generated by NO production.


Stereotactic biopsy combined with stereotactic (125)iodine brachytherapy for diagnosis and treatment of locally recurrent single brain metastases.
This paper reports on stereotactic biopsy combined with stereotactic (125)iodine brachytherapy (SBT) for locally recurrent, previously irradiated cerebral metastases, focusing on feasibility, complications, cerebral disease control, and survival. All patients with suspected locally recurrent metastases detected by MRI were selected for this combined procedure. After stereotactic biopsy, all patients with a verified vital tumor underwent SBT (50 Gy surface dose applied for 42 days) during the same surgical procedure. Histological results of biopsy, complications, treatment response, local and distant disease control, and survival were evaluated. Thirty patients underwent stereotactic biopsy, and 27 were treated with SBT for histologically proved tumor recurrence. There was no treatment-related mortality, and morbidity was transient and low (6.6%). Median survival was 14.8 months. After one year the actuarial incidence of local and distant relapse was 6.7 and 45.5%, respectively. There was no grade 3 or 4 CNS toxicity, even among the 18.5% of patients with tumors >30 mm. For these patients stereotactic biopsy seems to be a safe and valuable means of differentiating between radiation-induced tissue changes and tumor recurrence/progression. SBT is a safe, minimally invasive, and highly effective treatment option for cerebral disease control and survival. Furthermore, it can be performed during the same stereotactic operation.


Improved laboratory efficiency and diagnostic accuracy with new double-lumen-protected swab for for endometrial specimens.
Intrauterine specimens were obtained from 22 patients with endometritis and 24 control patients following cesarean section by using both a new protected swab and a standard anaerobic swab. The protected swab improved the value of the direct smear and Gram stain, resulted in fewer false-positive cultures, better defined endometrial flora in patients with endometritis, and permitted major savings in laboratory personnel time and materials.


Assessing the effects of environmental toxicant exposure in developmental epidemiological studies: issues for risk assessment.
Epidemiological studies have been of critical importance to the understanding of the effects of environmental chemical exposure during development on the behavior of infants and children. The ultimate goal of these studies should be to provide information that may be used directly for the protection of public health. The strategies for the assessment endpoints include development of domain-specific tests based on knowledge concerning effects of the chemicals being assessed, or use of standard clinical instruments that sample a range of functions. Discussion of an overall strategy for choice of endpoints would allow more straightforward comparisons across studies. There is increasing recognition of the importance of measuring a number of chemicals relevant to the population under study; however, different investigators make different decisions concerning which and how many chemicals to measure, as well as how to include them in the statistical analysis, particularly when there is a high degree of collinearity. Chemicals that are highly correlated with the "chemical of interest" are sometimes not included in the statistical analysis, resulting in missed opportunity to derive important information from the study. In addition, the shape of the relationship between exposure and effect is usually not explored in epidemiological studies, even though such information is critical for risk assessment. Opportunity for discussion among investigators, statisticians, and risk assessors potentially would result in human developmental toxicity studies being maximally useful for public health decisions.


A new type of NADH model compound: synthesis and enantioselective reduction of benzoylformates to the corresponding mandelates.
A new type of NADH model compound with good reactivity and enantioselectivity has been synthesized in good yields by an efficient and convenient synthetic method. The structures of these model compounds were confirmed by 1H and 13C-NMR and MS.


Bixin and norbixin in human plasma: determination and study of the absorption of a single dose of Annatto food color.
A procedure was developed for the detection and determination of bixin and norbixin in human plasma by reversed-phase HPLC with a sensitivity limit of 5 micrograms l-1. A group of seven volunteers ingested a single dose of 1 ml of a commercial Annatto Food Color (16 mg of cis-bixin in soybean oil). The presence of bixin (cis and trans) and norbixin (cis and trans) was demonstrated in the plasma at average levels of 11.6, 10.1, 2.8 and 0 micrograms l-1 of bixin and 48, 58, 53 and 29 micrograms l-1 of norbixin after 2, 4, 6 and 8 h, respectively. Considerable individual variations were observed. Complete plasma clearance generally occurred for bixin by 8 h and for norbixin by 24 h after ingestion of cis-bixin.


Lack of effect of choline and narcotic antagonists upon apomorphine discrimination.
Rats were trained to discriminate between the stimulus properties of intraperitoneal 0.16 mg/kg apomorphine and saline in a two-lever, food-motivated operant task. Subjects were then injected with either 79 mg choline chloride, 0.02 mg/kg haloperidol, 10 mg/kg naloxone or 10 mg/kg naltrexone prior to apomorphine or saline discriminative testing. Only haloperidol pretreatment was observed to significantly alter the rats' ability to discriminate apomorphine. The results are discussed in relation to the possible mechanism(s) of action of narcotic antagonist and cholinomimetic drug effects upon dopaminergically mediated behaviors.


Effect of gabapentin on fetal rat brain and its amelioration by ginger.
Intrauterine exposure to antiepileptic drugs (AEDs) is associated with neurodevelopmental alterations causing postnatal behavioral and cognitive alterations. These disorders are associated with the interference of these AEDs with the developing cerebral cortex and hippocampal neurons. Therefore, it is crucial to identify the drugs that should be avoided during pregnancy in order to prevent AED mediated developmental alterations. The present study was conducted to investigate the effects of prenatal exposure to the antiepileptic drug gabapentin (GBP) on the rat fetal brain during the organogenesis phase and to examine the potential ameliorative effect of ginger (Zingiber officinale). Consequently, the current study addressed the developmental neural changes on the histological, immuno-histochemical and ultrastructural levels. The brain of fetuses from the GBP group showed a highly significant decrease in their weight. Histologically, the cerebral cortex and hippocampus regions of fetuses maternally injected with GBP showed layer disorganization, vacuolated neuropil and massive cell degeneration. The expression of Caspase 3 was significantly increased in the brain of GBP fetuses, unlike the expression of Bcl-2 which was significantly decreased. On the ultrastructure level, the neurons showed pyknotic and chromatolytic nuclei. The cytoplasm was rarefied with swollen organelles. Co-administration of ginger evidently ameliorated most of these effects. In conclusion, GBP administration during pregnancy could possibly affect the developing fetal brain and ginger may have ameliorating effect against the induced GBP neurotoxicity and should be taken in parallel.


Angiogenesis imaging study using interim [18F] RGD-K5 PET/CT in patients with lymphoma undergoing chemotherapy: preliminary evidence.
Our aim was to measure the impact of two cycles of standard chemotherapy on tumoural neoangiogenesis by [18F] fluorine arginine-glycine-aspartic (RGD-K5) positron emission tomography-computed tomography (PET) on patients presenting with lymphoma. Nineteen patients at Rouen's Henri Becquerel Cancer Centre were prospectively included. Fluorodeoxyglucose (FDG) and RGD-K5 PET were performed before (C0) and after (C2) two cycles of chemotherapy. End-of-treatment FDG PET was performed for final evaluation. Maximum standardised uptake value (SUVmax), SUVmean, Metabolic Tumour Volume (MTV) and Angiogenic Tumour Volume (ATV) were measured for all lesions. RGD SUVmax and SUVmean were also analysed in 13 normal organs at C0 and C2. The patient's treatment response was considered using the Deauville score (DS) at the end of FDG PET treatment (DS 1-3 were considered responders, and 4 and 5 non-responders). Eighteen patients had both C0 FDG and RGD PET. Twelve patients had both C2 FDG and RGD, completed the treatment protocol and were included in end-of-treatment analysis. No statistical difference was found in RGD uptake of normal organs before and after chemotherapy for SUVmax and SUVmean. On C0 RGD, apart from classical Hodgkin lymphoma (cHL; n = 5) and grey zone lymphoma (GZL; n = 1), other lymphoma sub-types (n = 12) had low RGD uptake (p < 0.001). Regarding FDG, there was no significant difference for SUVmax, SUVmean and MTV at C0 and C2 between patients with cHL and non-Hodgkin lymphoma (NHL). At C2 RGD, non-responders had higher SUVmax and SUVmean compared to responders (p < 0.001). There was no significant difference in RGD ATV between responders and non-responders. Our study showed significant higher initial RGD uptake in patients presenting with cHL and GZL compared to NHL. Non-responder also had higher post-chemotherapy RGD uptake compared to responders. Issues raised by RGD uptake, particularly in cHL, are yet to be explored and need to be confirmed in a larger population.


Anxiety, social support and satisfaction of patients' families in intensive care units: A descriptive-correlational study.
This study was conducted with family members of patients' in the intensive care unit (ICU) to identify their anxiety level, social support and satisfaction with the ICU. Admission of critical patients to the ICU usually involves the participation of family members. A descriptive-correlational design was used and reported according to the STROBE checklist. The sample consisted of 250 family members in ICUs in a city of Turkey. Data were collected by the Multidimensional Perceived Social Support Scale, the State-Trait Anxiety Inventory and the Family Satisfaction in the Intensive Care Unit scale. A negative correlation was found between family satisfaction of the ICU and state anxiety (r = -0.349, p < 0.001), and a negative relationship between the satisfaction of the ICU and trait anxiety of the participants (r = -0.151, p < 0.05). There was a significant relationship between the state anxiety level (Adjusted R² = 0.080, F = 8.247, p < 0.001), trait anxiety level (Adjusted R² = 0.185, F = 19.821, p < 0.001), the perceived social support (Adjusted R² = 0.094, F = 9.640, p < 0.001) and satisfaction (Adjusted R² = 0.013, F = 4.161, p < 0.001) of family members and their sociodemographic characteristics. The study concluded that anxiety levels of relatives of the families were high, their social support and satisfaction with the intensive care unit were at a moderate level. There was a correlation between anxiety levels, satisfaction with the intensive care unit, and the perceived social support of families. Holistic care for the psychosocial needs of families who have a member in the ICU should be planned to increase satisfaction. Nurses should observe families closely for anxiety, allow them to ask questions and include them in the care of their family member.


Analgesic synergism between intrathecal morphine and cyclooxygenase-2 inhibitors in mice.
The analgesic effects of the intrathecal coadministration of morphine with nimesulide, meloxicam and parecoxib, preferential cyclooxygenase-2 (COX-2) inhibitors, were studied in mice using a chemical model of visceral pain, the acetic acid writhing test. Isobolographic analysis was used to characterize the interactions between mixtures of morphine with each non-steroidal anti-inflammatory drug. Antinociception dose-response curves were analyzed to obtain the ED50's of each drug. A dose response curve for fixed ratio mixtures of morphine with COX-2 inhibitors was then performed and the observed ED50's were plotted on a two-dimensional isobologram. All the combinations tested showed synergistic interactions and the strength of the interaction was ranked as: morphine/parecoxib>morphine/meloxicam>morphine nimesulide. The results demonstrate that the intrathecal coadministration of COX-2 inhibitors significantly enhance morphine-induced antinociception and could result in an opioid sparing action which may be useful in the clinical treatment of severe pain. A sparing action means that less opioids have to be administered to obtain a given analgesic effect. Since intrathecal morphine is often used in clinical pain situations, the opioid sparing effect resulting from the synergy observed with the coadministration of COX-2 inhibitors may be clinically relevant. One of the most significant advantages should be the reduction of opioid toxicity which often acts as a major obstacle in pain treatment.


Pd(NHC)(cinnamyl)Cl-catalyzed Suzuki cross-coupling reaction of aryl sulfonates with arylboronic acids.
A series of N-heterocyclic carbene (NHC)-palladium catalysts have been synthesized and applied to catalyze the Suzuki coupling reaction efficiently between aryl sulfonates and arylboronic acids with the potassium phosphate heptahydrate as a base. The desired yields are obtained even with less reactive aryl tosylates or aryl mesylates as substrates. This method was applied successfully to the synthesis of the (R)-2-(t-butoxycarbonylamino)-3-(biphenyl-4-yl)-propan-1-ol which is the key intermediate of sacubitril, a component of the newly approved antihypertensive drug "Entresto."


Differences in the susceptibility to cadmium-induced renal tubular damage and osteoporosis according to sex.
This study aimed to estimate the risks for renal tubular damage and osteoporosis in individuals with long-term environmental Cd exposure. This cross-sectional study comprised 1086 residents living in the vicinity of a copper refinery plant. As the urinary Cd levels increased, the proportion of female subjects with β₂-MG ≥300 μg/g creatinine also increased significantly, but this was not observed in the male subjects. The prevalence of osteoporosis was significantly higher in men with urinary Cd >5 μg/g creatinine than in those with urinary Cd ≤5 μg/g creatinine. This difference was not observed in the corresponding female groups. The association between increased urinary excretion of β₂-MG and decreased BMD was statistically significant only in the female subjects. We suggest that an increased Cd body burden directly decreases the BMD in male subjects; however, in female subjects, it first induces renal microtubular damage, which can lead to osteoporosis.


COVID-19 containment on a college campus via wastewater-based epidemiology, targeted clinical testing and an intervention.
Wastewater-based epidemiology has potential as an early-warning tool for determining the presence of COVID-19 in a community. The University of Arizona (UArizona) utilized WBE paired with clinical testing as a surveillance tool to monitor the UArizona community for SARS-CoV-2 in near real-time, as students re-entered campus in the fall. Positive detection of virus RNA in wastewater lead to selected clinical testing, identification, and isolation of three infected individuals (one symptomatic and two asymptomatic) that averted potential disease transmission. This case study demonstrated the value of WBE as a tool to efficiently utilize resources for COVID-19 prevention and response. Thus, WBE coupled with targeted clinical testing was further conducted on 13 dorms during the course of the Fall semester (Table 3). In total, 91 wastewater samples resulted in positive detection of SARS-CoV-2 RNA that successfully provided an early-warning for at least a single new reported case of infection (positive clinical test) among the residents living in the dorm. Overall, WBE proved to be an accurate diagnostic for new cases of COVID-19 with an 82.0% positive predictive value and an 88.9% negative predictive value. Increases in positive wastewater samples and clinical tests were noted following holiday-related activities. However, shelter-in-place policies proved to be effective in reducing the number of daily reported positive wastewater and clinical tests. This case study provides evidence for WBE paired with clinical testing and public health interventions to effectively contain potential outbreaks of COVID-19 in defined communities.


Long-term follow-up of facilitated subcutaneous immunoglobulin therapy in multifocal motor neuropathy.
To assess the feasibility, efficacy and patient satisfaction of long-term facilitated subcutaneous immunoglobulin therapy (fSCIG) in multifocal motor neuropathy (MMN). Twelve patients previously participating in a randomized trial investigating the short-term efficacy of fSCIG were offered to switch to fSCIG maintenance therapy following a variable interval on conventional subcutaneous immunoglobulin. Eight patients were switched to fSCIG maintenance therapy, seven of whom were invited for a follow-up assessment after 18 months (range 13-23 months) of treatment. The age at follow-up was 57 years (range 45-70 years) and patients received a median weekly dose immunoglobulin G of 32.5 g (range 20.0-50.0 g), the dose being unaltered compared to baseline values following completion of the fSCIG trial. In five patients the infusion was biweekly, whereas two patients were infused weekly. The follow-up mean isometric strength normalized to pre-trial values was 107.7% (95% CI 86.4-129.0%) being non-inferior to baseline values (104.7%, 95% CI 97.6-111.8%, P = 0.015). The mean ODSS was 2.0 (95% CI 0.8-3.2) which is identical to the baseline score following completion of the fSCIG trial, the P-value for non-inferiority being <0.0001. The secondary variables of impairment, function and quality of life at follow-up all were non-inferior to baseline values (P ≤ 0.046). fSCIG seems feasible and effective for long-term maintenance treatment in patients with MMN.


How Do We Choose? A Review of Residency Application Scoring Systems.
As the USMLE Step 1 Board exam moves to a pass/fail system there will be fewer objective measurements available to evaluate students applying to residency programs. Thus, there is a need for a reliable, validated method of screening applicants based on all areas of their application. To this end, we conducted a literature review search to examine previously described residency application screening tools. A PubMed search was conducted using the keywords "residency," "applicant," "scoring," "algorithm," and "ranking." The search was limited to the last 10 years, and only articles written in English with the full-text available were included. The initial search yielded 512 results. Titles and abstracts were evaluated for inclusion and 11 articles met criteria for full-text evaluation. An additional 6 articles were excluded with reason following the full-text evaluation. A total of 5 papers were included in our descriptive analysis. Villwock et al. used the open-source STAR algorithm to create an initial interview list based on program-specific desirable attributes. Bowe et al. attempted to develop a screening tool based on the 6 ACGME competencies that could accurately predict a resident's performance. Similarly, Lyons et al. worked with an outside consulting firm to develop a screening tool that used several situational judgment questions to assess desired competencies for first year residents. Schenker et al. developed an evaluation process that used a combination of a standardized screening tool and semistructured interviews to produce a final rank list. Hu et al. created a screening tool for pharmacology residency applicants based on specific domains. Several residency application scoring systems have been evaluated for use in the initial screening process, but there is no consensus on which system is superior and whether or not those systems are successful in selecting the "best" candidates.


Analyzing and Comparing Omicron Lineage Variants Protein-Protein Interaction Network Using Centrality Measure.
The Worldwide spread of the Omicron lineage variants has now been confirmed. It is crucial to understand the process of cellular life and to discover new drugs need to identify the important proteins in a protein interaction network (PPIN). PPINs are often represented by graphs in bioinformatics, which describe cell processes. There are some proteins that have significant influences on these tissues, and which play a crucial role in regulating them. The discovery of new drugs is aided by the study of significant proteins. These significant proteins can be found by reducing the graph and using graph analysis. Studies examining protein interactions in the Omicron lineage (B.1.1.529) and its variants (BA.5, BA.4, BA.3, BA.2, BA.1.1, BA.1) are not yet available. Studying Omicron has been intended to find a significant protein. 68 nodes represent 68 proteins and 52 edges represent the relationship among the protein in the network. A few centrality measures are computed namely page rank centrality (PRC), degree centrality (DC), closeness centrality (CC), and betweenness centrality (BC) together with node degree and Local clustering coefficient (LCC). We also discover 18 network clusters using Markov clustering. 8 significant proteins (candidate gene of Omicron lineage variants) were detected among the 68 proteins, including AHSG, KCNK1, KCNQ1, MAPT, NR1H4, PSMC2, PTPN11 and, UBE21 which scored the highest among the Omicron proteins. It is found that in the variant of Omicron protein-protein interaction networks, the MAPT protein's impact is the most significant.


Burden of musculoskeletal disease and its determination by urbanicity, socioeconomic status, age, and sex: Results from 14,507 subjects.
The availability of reliable estimates of the burden of musculoskeletal disease is of considerable importance for policymakers. This study uses data from the 14,507 participants of the European Health Interview Survey conducted in Austria in 2006/2007 to calculate estimates of the prevalence of osteoarthritis, spinal conditions, and osteoporosis in a population representative of other European Union or Organisation for Economic Co-operation and Development member states. Urbanicity, socioeconomic status, and age and sex were included as determinants of musculoskeletal disease. The prevalence of arthritis was 18.8% (95% confidence interval [95% CI] 18.2-19.4%), of spinal conditions was 38.4% (95% CI 37.6-39.2%), and of osteoporosis was 6.6% (95% CI 6.3-7.0%). The census data showed strong evidence for an association between urbanicity and arthritis (P = 0.012) and osteoporosis (P < 0.001), but not spinal conditions (P = 0.721). Arthritis and spinal conditions were associated with socioeconomic status (P < 0.001 for all). Osteoporosis showed the same associations with age, income, and education. For arthritis, a combined model showed a substantial attenuation of the effect of urbanicity on arthritis prevalence after adjustment for socioeconomic status. These data suggest that the burden of musculoskeletal disease is determined by both urbanicity and socioeconomic status; however, the effect of urbanicity seems to be attributable to differences in socioeconomic status and demographics across geographic regions.


T cell activation and immune synapse organization respond to the microscale mechanics of structured surfaces.
Cells have the remarkable ability to sense the mechanical stiffness of their surroundings. This has been studied extensively in the context of cells interacting with planar surfaces, a conceptually elegant model that also has application in biomaterial design. However, physiological interfaces are spatially complex, exhibiting topographical features that are described over multiple scales. This report explores mechanosensing of microstructured elastomer surfaces by CD4+ T cells, key mediators of the adaptive immune response. We show that T cells form complex interactions with elastomer micropillar arrays, extending processes into spaces between structures and forming local areas of contraction and expansion dictated by the layout of microtubules within this interface. Conversely, cytoskeletal reorganization and intracellular signaling are sensitive to the pillar dimensions and flexibility. Unexpectedly, these measures show different responses to substrate rigidity, suggesting competing processes in overall T cell mechanosensing. The results of this study demonstrate that T cells sense the local rigidity of their environment, leading to strategies for biomaterial design.


High-risk lesions of the breast: concurrent diagnostic tools and management recommendations.
Breast lesions with uncertain malignant behavior, also known as high-risk or B3 lesions, are composed of a variety of pathologies with differing risks of associated malignancy. While open excision was previously preferred to manage all high-risk lesions, tailored management has been increasingly favored to reduce overtreatment and spare patients from unnecessary anxiety or high healthcare costs associated with surgical excision. The purpose of this work is to provide the reader with an accurate overview focused on the main high-risk lesions of the breast: atypical intraductal epithelial proliferation (atypical ductal hyperplasia), lobular neoplasia (including the subcategories lobular carcinoma in situ and atypical lobular hyperplasia), flat epithelial atypia, radial scar and papillary lesions, and phyllodes tumor. Beyond merely presenting the radiological aspects of these lesions and the recent literature, information about their potential upgrade rates is discussed in order to provide a useful guide for appropriate clinical management while avoiding the risks of unnecessary surgical intervention (overtreatment).


Novel GUS expression patterns following transposition of an enhancer trap Ds element in Arabidopsis.
Enhancer trap derivatives of the maize Dissociation (Ds) transposon were introduced into Arabidopsis thaliana. The enhancer trap Ds was so designed that upon transposition to sites containing regulatory sequences in adjacent genomic DNA, transcription of a Ds-borne beta-glucuronidase (GUS) gene would be activated. Sixty percent of all transposition events were associated with GUS expression patterns including one linked to a mutant phenotype. Patterns of GUS expression were found in various organs and were stably inheritable in the F4 and F5 progenies. These results demonstrate the potential value of the technique as a means for detection of developmentally regulated genes and analysis of their function. The enhancer trap construct used in our experiments, as well as the seeds of primary transformants are publicly available.


Attitudes toward strategies to increase organ donation: views of the general public and health professionals.
The acceptability of financial incentives for organ donation is contentious. This study sought to determine (1) the acceptability of expense reimbursement or financial incentives by the general public, health professionals involved with organ donation and transplantation, and those with or affected by kidney disease and (2) for the public, whether financial incentives would alter their willingness to consider donation. Web-based survey administered to members of the Canadian public, health professionals, and people with or affected by kidney disease asking questions regarding acceptability of strategies to increase living and deceased kidney donation and willingness to donate a kidney under various financial incentives. Responses were collected from 2004 members of the Canadian public October 11-18, 2011; responses from health professionals (n=339) and people with or affected by kidney disease (n=268) were collected during a 4-week period commencing October 11, 2011. Acceptability of one or more financial incentives to increase deceased and living donation was noted in >70% and 40% of all groups, respectively. Support for monetary payment for living donors was 45%, 14%, and 27% for the public, health professionals, and people with or affected by kidney disease, respectively. Overall, reimbursement of funeral expenses for deceased donors and a tax break for living donors were the most acceptable. The general public views regulated financial incentives for living and deceased donation to be acceptable. Future research needs to examine the impact of financial incentives on rates of deceased and living donors.


Developing an SMS text message intervention on sexual and reproductive health with adolescents and youth in Peru.
Improved access to sexual and reproductive health (SRH) services and information is essential for supporting adolescents and youth in making informed decisions and optimizing each young person's outcomes related to their SRH, health and well-being and countries' current and future social and economic development. Mobile phones offer opportunities for young people to privately access SRH content and to be linked to SRH services. The objective of this study was to develop the content for an SMS (short message service or "text message") platform jointly with adolescents and youth in three regions in Peru (Lima, Ayacucho and Loreto) as part of the ARMADILLO (Adolescent/Youth Reproductive Mobile Access and Delivery Initiative for Love and Life Outcomes) Study. Content development was done in three stages. During Stage 1, we held community consultations with 13-17 year old adolescents, 18-24 year old youth and professionals who work with young people through the education and health sectors ("adult advisers") to identify and rate SRH topics of interest through group free- and guided-brainstorming activities and an individual written sharing activity. During Stage 2, the team developed the preliminary domains, sub-domains and content for the SMS platform. During Stage 3, we held focus groups with adolescents to validate the SMS content, including both individual scoring of and group feedback for each SMS. Group feedback asked about their general impressions and understanding and their thoughts about the language and usefulness of the SMS. A total of 172 adolescents and youth ages 13-24 and 20 adult advisers participated. Adolescents and youth brainstormed and rated SRH topics and sub-topics that led to the initial structure for the SMS platform, with 9 domains, 25 sub-domains and 146 draft SMS. Adolescents provided high scores for the SMS, with all sub-domains receiving average scores of 3.0 or higher (out of 4.0) for the SMS included. Adolescents also provided suggestions to optimize content, including improvements to unclear messages, resulting in SMS with adolescent-friendly content in simple, straightforward language. This process also revealed that adolescents lacked knowledge and had misconceptions related to contraceptive methods. This study details the systematic process used to develop relevant and accessible SRH information through a participatory approach. We document critical information about what young people know and how they think, enabling us to understand their perspective and literally speak their language. Results also provide future directions for programmatic, research and policy efforts with young people, in particular around gender norms, interpersonal violence, and access to SRH information and services, in similar settings.


[The decalcification of teeth for histological studies by means of ultrasonics].
In order to accelerate decalcification of hard tissues for histological examinations, the additional application of ultrasonics is sometimes recommended. Comparative studies show that decalcification is not acclerated by ultrasonics.


C-terminal domain of CagX is responsible for its interaction with CagT protein of Helicobacter pylori type IV secretion system.
Helicobacter pylori are the well known human pathogen associated with gastric cancer and peptic ulcer. Pathogenesis is mainly due to the presence of 40 kb cagPAI (cag Pathogenicity Island) region that encodes the type IV secretion system (TFSS) consisting of a cytoplasmic part, a middle part/core complex (spans from inner membrane to outer membrane), and an outer membrane associated part. CagX and CagT are two important proteins of TFSS that have homology with virB9 and virB7 of Agrobacterium tumefaciens TFSS. In this study, we have shown that the CagX and CagT interact directly by using co-immunoprecipitation of endogenous CagX and CagT and MBP pull down assay. We further authenticate this observation using yeast two-hybrid assay and co-expression of both the protein coding gene in Escherichia coli. We also observed that the C-terminal region of CagX is important for CagT interaction. We reconfirm that CagT depends on CagX for its stabilization. These observations could contribute in overall visualization of assembly and architecture of TFSS because protein-protein interactions among Cag proteins are likely to have an important role in assembly. Thorough understanding about architecture and mechanism of action of cag-TFSS may lead to design controlled drug delivery system.


Quantifying the effect of health status on health care utilization using a preference-based health measure.
The purpose of this study was to quantify the effect of health status on current and future payments and number of visits to health professionals in a large, representative community sample in British Columbia, Canada. The study population was comprised of all respondents to the 1994/5 cycle of the Canadian National Population Health Survey (NPHS) who were 12 years of age or older and residing in the province of British Columbia (N = 2084). Health status was measured with the Health Utilities Index (HUI). Two outcomes were defined for each subject: (a) the sum of all healthcare costs covered by the Medical Services Plan, incurred during a given fiscal year, and (b) the total number of visits to all health practitioners during the same year. Outcome data were obtained for a period 1994-1998. We examined the relationship between the HUI and healthcare use in a multivariate log-linear model. In the full sample, better health in 1994-1995 was associated with lower healthcare cost and lower number of visits from 1994 through 1998. The overall adjusted cost ratio was 0.89 (99% CI = 0.85, 0.94) and the overall adjusted visit ratio was 0.91 (99% CI + 0.87, 0.95). The effect of health status on the costs of care and on the number of visits was similar in men and women, was stronger in persons less than 45 years of age compared to those 45+, and was not different according to place of residence. We conclude that the HUI is a strong predictor of health services use over 5 years. A 0.1 improvement in health utility is associated with a 10% reduction in the costs of care and number of visits to health professionals.


Prevalence and treatment of silent gastro-oesophageal reflux in children with recurrent respiratory disorders.
Thirty-six infants and children presenting with recurrent respiratory disorders (RRD) as the sole clinical symptom including bronchial asthma (6), recurrent obstructive bronchitis with or without wheezing (18), chronic nocturnal cough (3), recurrent episodes of pneumonia (3), recurrent pharyngitis (3) and recurrent laryngitis (3) were investigated for associated gastro-oesophageal reflux (GER) by oesophagram, endoscopy and continuous 24 h pH monitoring of the distal oesophagus. The pH monitoring criteria were selected on the basis of a preliminary study comparing statistically measurements of 32 variables recorded in 15 patients who all had clinical, radiological and endoscopic evidence of GER and in 8 asymptomatic controls. Although patients with symptomatic GER differed significantly from the asymptomatic ones for 27 variables examined, 6 variables emerged as having the highest value for discrimination (overlap score 0-1). Among these, the Euler-Byrne index (number of reflux pH less than 4 + 4 times the number of reflux episodes of more than 5 min), the percentage of total reflux time and the number of reflux episodes 1 h post-cibal scored 0 (no overlap). GER was considered to be present when at least five of these six parameters were abnormal. The overall incidence of GER in children with RRD was 41% (15) when detected by oesophagram and 61% (22) when diagnosed by pH monitoring criteria. In the children with bronchial asthma or with recurrent laryngitis, the percentage of reflux time during sleep was about 40 times higher than in asymptomatic controls and 2 times higher than in those with symptomatic GER.(ABSTRACT TRUNCATED AT 250 WORDS)