Quantification of age pigments (lipofuscin).
1. Three methods have hitherto been applied for age pigment quantification: (a) numerically from micrographs; (b) fluorimetrically from histological sections; (c) spectrofluorimetrically from dissolved age pigments. 2. The spectrofluorimetric method is at present the most commonly used technique for quantification of age pigments. 3. By comparing the related publications since introduction of the spectrofluorimetric method, it has become apparent that few authors specify fluorimetrically significant factors, such as temperature and pH which influence the sample fluorescence during measurement. 4. Recent developments in fluorimetrical age pigment quantification using chloroform/methanol as solvent have additionally revealed the necessity to measure and present the age pigments dissolved in both phases: the polar and non-polar solvents.


[Possibilities of adjuvant drug therapy in replantation surgery].
Additional therapy after replantation of extremities is reported. The therapy is based on the pathophysiological changes in hypoxic tissue. The management has been tested in clinical practice.


Percent right ventricular pacing predicts outcomes in the DAVID trial.
The Dual-Chamber and VVI Implantable Defibrillator (DAVID) trial demonstrated a worse outcome in patients with implantable cardioverter-defibrillators (ICDs) programmed to DDDR at 70 bpm compared with patients who had ICDs programmed to VVI backup pacing at 40 bpm. Pacing was more frequent in the DDDR group. The purpose of this study was to determine whether right ventricular pacing (RV) is an independent predictor of outcome in the DAVID trial. We evaluated the relationship of percent RV pacing to the composite endpoint of death or hospitalization for congestive heart failure. Patients who had a 3-month follow-up and who had not yet reached an endpoint were included in the study. Using Cox regression analysis (VVI group N = 195; DDDR group N = 185), we examined multiple factors, including percent RV pacing at 3-month follow-up, that might be associated with adverse outcomes. Percent RV pacing as a continuous variable was correlated with the primary endpoint. As a dichotomous variable, the best separation for predicting endpoints occurred with DDDR RV pacing > 40% vs DDDR RV pacing < or = 40% (P = .025). Patients with DDDR RV pacing < or = 40% had similar or better outcomes to the VVI backup group (P = .07). Correction for baseline variables predictive of the composite outcome in the (nonpaced) VVI group (use of nitrates, increased heart rate, and increased age) did not change the findings for RV pacing (P = .008). In contrast, atrial pacing was not predictive of worse outcomes. These results suggest, but do not prove, a causal relationship between frequent RV pacing and adverse outcomes in patients with left ventricular ejection fraction < or = 40%.


A zero-strain layered metal oxide as the negative electrode for long-life sodium-ion batteries.
Room-temperature sodium-ion batteries have shown great promise in large-scale energy storage applications for renewable energy and smart grid because of the abundant sodium resources and low cost. Although many interesting positive electrode materials with acceptable performance have been proposed, suitable negative electrode materials have not been identified and their development is quite challenging. Here we introduce a layered material, P2-Na0.66[Li0.22Ti0.78]O2, as the negative electrode, which exhibits only ~0.77% volume change during sodium insertion/extraction. The zero-strain characteristics ensure a potentially long cycle life. The electrode material also exhibits an average storage voltage of 0.75 V, a practical usable capacity of ca. 100 mAh g(-1), and an apparent Na(+) diffusion coefficient of 1 × 10(-10) cm(-2) s(-1) as well as the best cyclability for a negative electrode material in a half-cell reported to date. This contribution demonstrates that P2-Na0.66[Li0.22Ti0.78]O2 is a promising negative electrode material for the development of rechargeable long-life sodium-ion batteries.


Limbic encephalitis in Taiwanese children and adolescence: a single center study.
Non-viral limbic encephalitis, which may be paraneoplastic or idiopathic, is increasingly recognized in adults and children. Early identification of potential patients, who have neuronal autoantibodies to intracellular or neuronal surface antigens in order to give appropriate immunotherapy, is key to improving the prognosis. This cross-sectional study describes the clinical manifestation and the serological evidence of the presence of neuronal antibodies in Taiwanese children with limbic encephalitis. We enrolled children and adolescents who had been hospitalized due to nonviral limbic encephalitis. Serum samples from these patients were collected to screen antibodies against intracellular antigens [amphiphysin, Ma2, Ri, Yo, Hu and antiglutamic acid decarboxylase (GAD)] and neuronal surface antigens [N-methyl-d-aspartate (NMDA) receptor, γ-amino butyric acid (GABAB) receptor and voltage-gated potassium channel complexes (VGKCs)]. All of the 10 enrolled patients had acute onset of fever and rapid clinical deterioration. They had persistent neuropsychiatric symptoms and 90% developed refractory epilepsy, despite six patients having been treated with methylprednisolone pulse therapy or intravenous immunoglobulin (IVIG) at the acute stage. In the laboratory findings, half of the cases were positive for antibodies with regards to intracellular antigens (amphiphysin or GAD). The general outcomes, assessed by Glasgow Outcome Scale, were similar between patients with and those without the antibodies (Mann-Whitney U test, p = 0.43). One patient, who was positive for antibodies to amphiphysin 10 years after disease onset, still had a significant response to oral prednisolone therapy. At the end of the follow-up period, no cancer or insulin-dependent diabetes mellitus was detected in any of the patients. This study provides evidence for a potential association between antibodies and limbic encephalitis. The presence of antibodies, especially antibodies to GAD, may serve as an indicator for immunotherapy.


Theory and implementation of sub-model method in finite element analysis.
Through finite element analysis (FEA) software to study mechanical performance of a bridge structure is currently a commonly used method. The keys to obtain accurate results are to select the appropriate element type and establish a refine mesh model. With the construction of a large number of kilometer-level long-span bridges in practical projects, the time cost of establishing and analyzing a fine mesh solid finite element model (FEM) of a long-span bridge with complex structure can not be ignored. In order to find the balance between accuracy and efficiency, sub-modeling technique can be used to analyze the bridge structure. It is often thought that the sub-modeling technique is only applicable to shell and solid elements, but in fact it is also applicable to plane frame models. Based on two-dimensional (2-D) beam element model, the theory of sub-model was theoretically deduced. Meanwhile the sub-modeling technique was applied and verified by an example of plane frame model. Furthermore, based on the three-dimensional (3-D) solid FEM of a skew bridge, the influence of mesh size on the calculation accuracy was illustrated. Based on sub-modeling technique of nodal displacements, the results of the global model and the sub-model for the skew bridge were compared and studied in terms of stress field and plastic damage of concrete. It is found that the sub-model technique based on nodal displacements is suitable for solid FEM.


Factors associated with self-report of polycystic ovary syndrome in the Coronary Artery Risk Development in Young Adults study (CARDIA).
Polycystic ovary syndrome (PCOS) is underdiagnosed, but factors associated with women's report of diagnosis are not well-understood, particularly social determinants of health. Therefore, in a population-based cohort, we compared the characteristics of women with self-reported PCOS vs. women who have unrecognized PCOS vs. women without PCOS. We performed a secondary data analysis of the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a population-based, prospective cohort of Black and White women. Participants were women (n = 2028) who responded to the question, "Did a doctor or nurse ever tell you that you had polycystic ovarian syndrome or polycystic ovarian disease?" at the year 15 examination. Women who answered "yes" were defined as having self-reported PCOS. Women who answered "no or not sure" were defined as having unrecognized PCOS if they also had irregular menses and hyperandrogenemia between 20 and 30 years of age. Exposures of interest included social determinants of health, symptoms including irregular menses and hirsutism, and comorbid conditions. Forty-three (2.1%) of women had self-reported PCOS, 135 (6.7%) had unrecognized PCOS, and 1850 (91%) women were without PCOS. In logistic regression models adjusting for age, race, and center, women with self-reported PCOS were more likely to have obesity (OR 1.83, 95% CI 1.22, 2.75) and diabetes (OR 2.37, 95% CI 1.05, 5.33) compared to women without PCOS. Women with unrecognized PCOS were more likely to have hypertension (OR 1.68, 95% CI 1.03, 2.74) and food insecurity (OR 1.94, 95% CI 1.25, 3.01) compared to women without PCOS. Unrecognized PCOS is common. Self-report of PCOS is not associated with access to healthcare. Women who report PCOS are more often obese and comorbidities may contribute to recognition of PCOS.


Fast moves in arbuscular mycorrhizal symbiotic signalling.
Exciting research looking at early events in arbuscular mycorrhizal symbioses has shown how the fungus and plant get together. Kohki Akiyama et al. have demonstrated that strigolactones in root exudates are fungal germ tube branching factors, and Arnaud Besserer et al. found that these compounds rapidly induce fungal mitochondrial activity. Andrea Genre et al. have shown that subsequent development of appressoria on host roots induces construction of a transient prepenetration apparatus inside epidermal cells that is reminiscent of nodulation infection.


Eye movement trajectories and what they tell us.
In the last two decades, research has shown that eye movement trajectories can be modified by situational determinants. These modifications can inform us about the mechanisms that control eye movements and they can yield information about the oculomotor, memory and attention system that is not easily obtained via other sources. Eye movement trajectories can deviate either towards or away from elements in the visual field. We review the conditions in which these deviations are found and the mechanisms underlying trajectory deviations. It is argued that deviations towards an element are caused by the unresolved competition in the oculomotor system between elements in a visual scene. Deviations away from an element are mainly observed in situations in which top-down preparation can influence the target selection process, but the exact cause of such deviations remains unclear.


Altered MHC class I presented peptide repertoire is not sufficient to induce NK cell mediated F1-hybrid resistance.
Murine NK cells are known to mediate F1-hybrid anti-parental graft rejection responses. This phenomenon has been linked to the MHC, and in particular, to the alpha 1/alpha 2 domains of the MHC class I molecules. Here, we have addressed the role of MHC class I bound peptides in NK cell mediated F1-hybrid anti-parental rejection by studying the resistance of F1-hybrids between B6 and different bm mutant strains to B6-derived RBL-5 lymphoma cell line. Tumor development occurred at a similar frequency in all combinations of (B6 x bm)F1 mice and control B6 mice. These results suggest that absence of a specific MHC class I presented peptide repertoire on grafted cells is not sufficient to induce NK cell mediated F1-hybrid anti-parental rejection responses.


[Effectiveness of the radiosensitizer cisplatin. A pilot study].
18 patients with advanced squamous cell carcinoma of the head and neck region were treated via chemotherapy and radio therapy. In this regimen cisplatinum was used as a radiosensitizer. The total remission rate was 94% while remission duration and survival could not be calculated. Severe clinical local toxicity occurred as a side effect.


Genetic Structure and Diversity in Wild and Cultivated Populations of the Mangrove Oyster Crassostrea gasar from Southern Brazil.
The mangrove oyster (Crassostrea gasar) is Brazil's second most cultured species and presents a high potential for aquaculture. However, artificial selection in a highly fecund species and significant variance in reproductive success can result in the loss of genetic diversity and increases the inbreeding rate, especially in cultivated populations. In this study, we investigated the genetic structure and diversity of C. gasar in wild and cultivated populations using 14 microsatellites. Spatial genetic comparisons revealed the existence of two main genetic groups of C. gasar, one comprising the population in cultivation and the other formed by wild populations along the southern and southeastern Brazilian coasts. Although no common genetic structure exists among wild populations, it is possible to observe a distribution gradient based on discriminant analysis of principal components consistent with their geographic distribution. However, it is insufficient to differentiate them genetically. Despite artificial reproduction, the genetic diversity values of the cultivated population remained relatively high and did not show a reduction. Therefore, monitoring the cultivated population and establishing reference values for genetic diversity will allow the adoption of strategies both for the viability of the cultivated population and the management of wild populations.


Adding cetuximab to paclitaxel and carboplatin for first-line treatment of carcinoma of unknown primary (CUP): results of the Phase 2 AIO trial PACET-CUP.
Patients with carcinoma of unknown primary (CUP) have a dismal prognosis, even when treated with multi-agent chemotherapy. We hypothesised that adding the epidermal growth-factor receptor (EGFR) inhibitor cetuximab to standard first-line chemotherapy with paclitaxel and carboplatin would improve PFS and RR in unfavourable CUP. This open-labelled, multicentre Phase 2 study included patients with unfavourable, untreated adeno- or undifferentiated CUP. Patients were randomised to receive either paclitaxel/carboplatin (group A) or paclitaxel/carboplatin plus cetuximab (group B) every 3 weeks for a maximum of 6 cycles followed by cetuximab maintenance in group B. The primary endpoint was PFS in the two groups. Secondary endpoints were RR, toxicity and overall survival (OS). One-hundred-and-fifty patients were randomised (group A = 72, group B = 78). The median PFS and OS for all patients were 3.8 and 8.1 months (95% confidence interval (CI): 2.9-4.8 and 6.8-9.5). There was no significant difference in PFS (3.7 vs 4.6 months, HR 0.98) or OS (8.1 vs 7.4, HR 1.1) between the two treatment groups. Response rate tended to be better for chemotherapy plus cetuximab compared to chemotherapy alone (22% vs 15%). Adverse events grade ≥3 were comparable between the two groups, except for significantly increased skin toxicity in the cetuximab arm. Cetuximab plus paclitaxel/carboplatin did not improve PFS, OS and RR in metastatic CUP compared to paclitaxel/carboplatin alone. Addition of cetuximab resulted in additional skin toxicity. The study was registered at clinicaltrials.gov as NCT00894569.


CoDNaS-RNA: a database of conformational diversity in the native state of RNA.
Conformational changes in RNA native ensembles are central to fulfill many of their biological roles. Systematic knowledge of the extent and possible modulators of this conformational diversity is desirable to better understand the relationship between RNA dynamics and function. We have developed CoDNaS-RNA as the first database of conformational diversity in RNA molecules. Known RNA structures are retrieved and clustered to identify alternative conformers of each molecule. Pairwise structural comparisons between all conformers within each cluster allows to measure the variability of the molecule. Additional annotations about structural features, molecular interactions and biological function are provided. All data in CoDNaS-RNA is free to download and available as a public website that can be of interest for researchers in computational biology and other life science disciplines. The data underlying this article are available at http://ufq.unq.edu.ar/codnasrna or https://codnas-rna.bioinformatica.org/. Supplementary data are available at Bioinformatics online.


Verrucous carcinoma of the larynx: problems of diagnosis and treatment.
The first report of a case of verrucous carcinoma from Africa is presented. Problems of diagnosis and treatment are highlighted and the need for co-operation between the clinician and the pathologist for an accurate diagnosis is emphasized.


Citrobacter diversus and neonatal brain abscess.
A 23-day-old infant presented with apnea and was found to have Citrobacter diversus meningitis and brain abscess. The organism persisted in brain abscess fluid for over 4 weeks despite adequate antibiotic therapy. Cranial computed tomography demonstrated persistent radiolucencies in both frontal lobes, and midline shift, long after completion of antibiotic therapy. Effective therapy of C. diversus meningitis and brain abscess may require use of an antibiotic active within phagocytes, and judicious surgical drainage. A high prevalence of brain abscess mandates cranial computed tomography for any infant with C. diversus meningitis.


Amino acid function and docking site prediction through combining disease variants, structure alignments, sequence alignments, and molecular dynamics: a study of the HMG domain.
The DNA binding domain of HMG proteins is known to be important in many diseases, with the Sox sub-family of HMG proteins of particular significance. Numerous natural variants in HMG proteins are associated with disease phenotypes. Integrating these natural variants, molecular dynamic simulations of DNA interaction and sequence and structure alignments give detailed molecular knowledge of potential amino acid function such as DNA or protein interaction. A total of 33 amino acids in HMG proteins are known to have natural variants in diseases. Eight of these amino acids are normally conserved in human HMG proteins and 27 are conserved in the human Sox sub-family. Among the six non-Sox conserved amino acids, amino acids 16 and 45 are likely targets for interaction with other proteins. Docking studies between the androgen receptor and Sry/Sox9 reveals a stable amino acid specific interaction involving several Sox conserved residues. The HMG box has structural conservation between the first two of the three helixes in the domain as well as some DNA contact points. Individual sub-groups of the HMG family have specificity in the location of the third helix, DNA specific contact points (such as amino acids 4 and 29), and conserved amino acids interacting with other proteins such as androgen receptor. Studies such as this help to distinguish individual members of a much larger family of proteins and can be applied to any protein family of interest.


Dipyridamole prevents the coconut oil-induced hypercholesterolemia. A study on lipid plasma and lipoprotein composition.
For a better understanding of the hypolipidemic function of dipyridamole, we have studied the comparative effects of diet supplementation with 10% coconut oil with and without dipyridamole on the lipid plasma and lipoprotein composition in chicks. This study was performed under postprandial and food-deprivation (12h) conditions. Coconut oil induced a clear hypercholesterolemia under both feeding conditions. Simultaneous administration of dipyridamole maintained total and esterified cholesterol at levels similar to those observed in control animals sacrificed under postprandial conditions. Under these conditions, our results also show that dipyridamole significantly reduced cholesterol levels in all the chick plasma lipoproteins that were increased by coconut oil administration. Nevertheless, it should be emphasised that the levels of total cholesterol found in intermediate- and very-low-density lipoproteins were lower than in control. All chemical components of these fractions were significantly decreased by dipyridamole. The effects were not significant in chicks deprived of food. In conclusion, our results show that the hypercholesterolemia induced by coconut oil was prevented by dipyridamole. To our knowledge, this is one of the first reports on the antihypercholesterolemic effects of dipyridamole.


Effect of pandemic-related debris on wildlife.
Georgina Mills reports on a study that used citizen science to assess the impact of litter from Covid-19 on wildlife.


A 4-hydroxybenzoate 3-hydroxylase mutant enables 4-amino-3-hydroxybenzoic acid production from glucose in Corynebacterium glutamicum.
Microbial production of aromatic chemicals is an attractive method for obtaining high-performance materials from biomass resources. A non-proteinogenic amino acid, 4-amino-3-hydroxybenzoic acid (4,3-AHBA), is expected to be a precursor of highly functional polybenzoxazole polymers; however, methods for its microbial production have not been reported. In this study, we attempted to produce 4,3-AHBA from glucose by introducing 3-hydroxylation of 4-aminobenzoic acid (4-ABA) into the metabolic pathway of an industrially relevant bacterium, Corynebacterium glutamicum. Six different 4-hydroxybenzoate 3-hydroxylases (PHBHs) were heterologously expressed in C. glutamicum strains, which were then screened for the production of 4,3-AHBA by culturing with glucose as a carbon source. The highest concentration of 4,3-AHBA was detected in the strain expressing PHBH from Caulobacter vibrioides (CvPHBH). A combination of site-directed mutagenesis in the active site and random mutagenesis via laccase-mediated colorimetric assay allowed us to obtain CvPHBH mutants that enhanced 4,3-AHBA productivity under deep-well plate culture conditions. The recombinant C. glutamicum strain expressing CvPHBHM106A/T294S and having an enhanced 4-ABA biosynthetic pathway produced 13.5 g/L (88 mM) 4,3-AHBA and 0.059 g/L (0.43 mM) precursor 4-ABA in fed-batch culture using a nutrient-rich medium. The culture of this strain in the chemically defined CGXII medium yielded 9.8 C-mol% of 4,3-AHBA from glucose, corresponding to 12.8% of the theoretical maximum yield (76.8 C-mol%) calculated using a genome-scale metabolic model of C. glutamicum. Identification of PHBH mutants that could efficiently catalyze the 3-hydroxylation of 4-ABA in C. glutamicum allowed us to construct an artificial biosynthetic pathway capable of producing 4,3-AHBA on a gram-scale using glucose as the carbon source. These findings will contribute to a better understanding of enzyme-catalyzed regioselective hydroxylation of aromatic chemicals and to the diversification of biomass-derived precursors for high-performance materials.


Ultrastructural studies on the morphogenesis of psammoma bodies in ovarian serous neoplasia.
Transmission electron microscopic studies have been carried out on psammoma bodies in two benign and seven malignant papillary serous neoplasms of the ovary. Ultrastructurally, psammoma bodies are composed of microcrystals in all respects similar to calcium-phosphate apatite crystals of bone. The formation of psammoma bodies is initiated intracellularly, in both the neoplastic epithelial cells and stromal histiocytes. The initial seeding site of apatite crystals is served by lipid-rich intracellular vesicles. These structures are produced in association with autophagocytosis in the neoplastic epithelial cells and heterophagocytosis of extracellular lipidic material in the stromal histiocytes. Extracellular lipids presumably derive from dehiscent tumor tissue. The close relationship between larger intraepithelial calcific bodies and microfilaments suggests that the latter provide supportive matrix for further intracellular calcification. Large extracellular psammoma bodies result from fused calcific bodies which have been extruded from calcified cells. Mineralization of extracellular collagen fibers is not observed. The results provide supportive evidence to the concept that psammoma bodies in ovarian papillary serous neoplasms and probably in other neoplastic and non-neoplastic conditions are a consequence of dystrophic calcification associated with cellular degeneration.


CCR2 deficiency decreases intimal hyperplasia after arterial injury.
Monocyte chemoattractant protein (MCP)-1 is upregulated in atherosclerotic plaques and in the media and intima of injured arteries. CC chemokine receptor 2 (CCR2) is the only known functional receptor for MCP-1. Mice deficient in MCP-1 or CCR2 have marked reductions in atherosclerosis. This study examines the effect of CCR2 deficiency in a murine model of femoral arterial injury. Four weeks after injury, arteries from CCR2(-/-) mice showed a 61.4% reduction (P<0.01) in intimal area and a 62% reduction (P<0.05) in intima/media ratio when compared with CCR2(+/+) littermates. The response of CCR2(+/-) mice was not significantly different from that of CCR2(+/+) mice. Five days after injury, the medial proliferation index, determined by bromodeoxyuridine incorporation, was decreased by 59.8% in CCR2(-/-) mice when compared with CCR2(+/+) littermates (P<0.05). Although leukocytes rapidly adhered to the injured arterial surface, there was no significant macrophage infiltration in the arterial wall of either CCR2(-/-) or CCR2(+/+) mice 5 and 28 days after injury. These results demonstrate that CCR2 plays an important role in mediating smooth muscle cell proliferation and intimal hyperplasia in a non-hyperlipidemic model of acute arterial injury. CCR2 may thus be an important target for inhibiting the response to acute arterial injury.


[Required competence in geriatrics in the view of the Competence Center for Geriatrics].
The geriatric patient is defined by a high specific risk that is taken into account by the special geriatric treatment concept. This risk relates to suffering from the permanent and significant loss of earlier functional independence caused by relatively trivial accessory conditions or other changes to the personal situation or falling in need of or increasing the need for care. It results from the geriatric patient's limited reserve capacities that are caused by physiological age-related limitations of organ and organ system reserves and/or manifested or at least latent functional impairments. A rather narrow definition of the geriatric patient based on this specific risk is a key criterion for the future systematic integration of geriatric care into the health service. In such a definition, use of the age component alone is adequate only from a very old age on. The high-risk group of geriatric patients narrowly defined in such a way also calls for primary medical geriatric case management: from commencement of a treatment throughout its entire course, from therapy to rehabilitation to longterm and outpatient care. This comprises first and foremost an comprehensive geriatric assessment and a treatment oriented primarily towards achieving quality of life and independence, medical treatment control including a systematic risk management system, continuous patient support, even in case of other temporary, specific treatments, the individual use of early rehabilitative treatments and the coordination of secondary treatment initiatives. Positioning geriatrics in the health care system in such a way means that the required skills extend beyond a general knowledge of geriatric medicine. Above all, high generic treatment expertise and experience in geriatric rehabilitation are also needed. Additionally, the guide and support function of the geriatrician demands a willingness to take special medical and ethical responsibility and an abundant ability to integrate and communicate. The education, training and development initiatives for attaining geriatric qualifications must satisfy these requirements. Lasting efficient geriatric care concepts also call for the appropriate skills in primary medical outpatient care.


We need to do better: Readability analysis of online patient information on cancer survivorship and fertility preservation.
National Institute of Health recommends that patient education material should be written at no greater than 6th-grade level. Cancer survivorship and fertility preservation discussion with patients is recommended by many national societies and being done more frequently. We sought to analyze online patient information on cancer survivorship and fertility preservation to see if they meet the criteria set by national guidelines. Online patient information on cancer survivorship and fertility preservation was collected and analyzed by six of the most common readability tests. Only websites in English and free to access were used. A total of 15 separate websites for cancer survivorship and fertility preservation was used. All websites failed to meet national guidelines. Cancer survivorship information was written at a high school senior and a 12th-grade level. Fertility preservation information was written at a high school-senior and junior college level. Online patient information on cancer survivorship and fertility preservation did not meet national guidelines. Testing across six of the most used readability indexes showed that information is challenging to understand for the general patient population. This article shares an insight into the complex and growing fields of cancer survivorship and fertility preservation. Educating patients about their condition is critical and improves outcomes and participation in shared decision making. Healthcare policy should focus on implementing a system that will provide culturally and linguistically appropriate information in the community for patients about their disease.


Synthesis of oligonucleotides carrying fluorescently labelled O(6)-alkylguanine for measuring hAGT activity.
O(6)-alkylguanine-DNA-alkyltransferase (hAGT) activity provides resistance to cancer chemotherapeutic agents and its inhibition enhances chemotherapy. We herein present the development of a novel fluorescence assay for the detection of hAGT activity. We designed a dsDNA sequence containing a fluorophore-quencher pair, where the fluorophore was attached to an O(6)-benzylguanine. This precursor was synthesized using the Mitsunobu reaction to introduce the benzyl group. The alkyl-fluorophore group is transferred to the active site during the dealkylation, producing an increase in fluorescence which is correlated to hAGT activity. This assay can be used for the evaluation of potential inhibitors of hAGT in a straightforward manner.


Integration of metal-organic frameworks into an electrochemical dielectric thin film for electronic applications.
The integration of porous metal-organic frameworks onto the surface of materials, for use as functional devices, is currently emerging as a promising approach for gas sensing and flexible displays. However, research focused on potential applications in electronic devices is in its infancy. Here we present a facile strategy by which interpenetrated, crystalline metal-organic framework films are deposited onto conductive metal-plate anodes via in situ temperature-controlled electrochemical assembly. The nanostructure of the surface as well as the thickness and uniformity of the film are well controlled. More importantly, the resulting films exhibit enhanced dielectric properties compared to traditional inorganic or organic gate dielectrics. This study demonstrates the successful implementation of the rational design of metal-organic framework thin films on conductive supports with high-performance dielectric properties.


High ammonia exposure regulates lipid metabolism in the pig skeletal muscle via mTOR pathway.
Ambient ammonia exposure has been known to perturb lipid metabolism in farm animals, but the underlying mechanism is unclear. The current study was conducted to investigate how ambient ammonia exposure influences lipid metabolism in the pig model. Twelve pigs were randomly divided into two groups, either exposed to 0 or 35 mg/m3 atmospheric ammonia for 25 days. Serum ammonia remained unchanged (p > 0.05), but increased serum urea concentration was found (p < 0.05) after ammonia exposure. Ammonia exposure also caused an increased C18:0, C18:2n6c, C18:3n6, C18:3n3, C20:0, C20:2, C20:3n6, C20:3n3, C22:0 concentrations and fat content in the longissimus dorsi muscle (p < 0.05), and also serum total triglyceride (p = 0.0294) and ApoB (p = 0.0061) contents. Analysis of serum free amino acids profile revealed that concentrations of ornithine, tyrosine, asparagine, histidine, phenylalanine, leucine, isoleucine, glutamine and valine were significantly increased in the pigs exposed to 35 mg/m3 ammonia (p < 0.05). RNA-Seq analysis showed that genes encoding enzymes involved in lipid synthesis (FASN, SCD and FADS1) and uptake (LDLR) were up-regulated, whereas genes related to lipolysis (PNPLA4, ANGPTL4 and CEL), transport (CPT1A, CPT1B and CPT2) and β-oxidation (ACADL, ACADVL, UCP2 and UCP3) were down-regulated. Furthermore, exposure to 35 mg/m3 atmospheric ammonia increased expression of mTOR (p = 0.0377) and its downstream P70S6K (p = 0.0139) and p-P70S6K (p = 0.0431), but decreased AMPK (p < 0.0001) and p-AMPK (p = 0.0071) in the longissimus dorsi muscle. In conclusion, high concentration of atmospheric ammonia exposure greatly interferes with amino acid metabolism, resulting in increased BCAAs and aromatic amino acids. The increased BCAAs production can up-regulate lipid synthesis and down-regulate β-oxidation by activating mTOR signaling and inhibiting AMPK signaling.


PKC-δ mediates TCDD-induced apoptosis of chondrocyte in ROS-dependent manner.
Exposure to dioxin-like compounds is associated with arthritis in humans. A recent study reported that 2,3,7,8,-tetrachlorodibenzo-p-dioxin (TCDD) induces apoptosis in chondrocytes, which is a critical event in the pathogenesis of cartilage disease. In this study, protein kinase C (PKC) signaling pathway was investigated to determine the mechanism of TCDD-induced rabbit articular chondrocyte apoptosis. TCDD exposure induced glutathione-mediated ROS generation and the translocation of PKC isozymes. Among the PKC isozymes tested, PKC-δ showed the most sensitive translocation. The translocation was then blocked by ROS inhibitors (trolox and N-acetyl cysteine), a PKC-δ inhibitor (rottlerin), a caspase-3 inhibitor (z-DEVD-fmk) or an AhR blocker (α-naphthoflavone). TCDD increased caspase-3 activity, the activating enzyme for PKC-δ, and prior treatment with trolox blocked such an increase. These results suggest that the translocation of PKC-δ was mediated by ROS-dependent caspase-3 activity. Pretreatment with rottlerin or trolox dampened TCDD-induced apoptosis of chondrocyte, as determined by TUNEL staining and ELISA. Taken together, this study suggests that ROS generation is an upstream event for TCDD-induced chondrocyte apoptosis and PKC-δ mediates the apoptotic processes through ROS-dependent caspase-3 activation. This is a first finding demonstrating the role of PKC-δ in chondrocyte apoptosis stimulated by an environmental pollutant. The results may contribute to understanding the mechanism of joint disease associated with the exposure of dioxin-like compounds and identifying a target for the therapeutic interventions.


[Value of real-time elastography to guide the systematic prostate biopsy in men with normal digital rectal exam].
The aim of this study was to evaluate whether real-time elastography-guided biopsy in comparison to grey-scale ultrasound improves prostate cancer detection in patients with an unremarkable digital rectal exam.A total of 231 patients suspicious for prostate cancer were prospectively randomised to transrectal real-time elastography- (126) or grey-scale ultrasound (105)-guided biopsy. The peripheral zone was divided into 6 sectors from base, mid-gland to apex. Lesions with reduced elasticity during real-time elastography and hypoechoic areas during grey-scale ultrasound were defined as suspicious for prostate cancer. Prostate biopsy was guided by real-time elastography (RTE) or grey-scale ultrasound (GSU) using a systematic 10-core approach. Suspicious lesions on RTE or GSU in the corresponding randomised group were targeted within each sector. Accuracy of cancer prediction and histopathological cancer detection rates were evaluated and compared between the 2 imaging modalitiesBaseline characteristics of patients undergoing real-time elastography and grey-scale ultrasound, including age, prostate-specific antigen and prostate volume were not significantly different statistically (p>0.05). Overall, prostate cancer was detected in 76 of 231 cases (32.9%). The cancer detection rate was significantly higher (p=0.007) in patients who underwent a biopsy using real-time elastography (40.5%) compared to the grey-scale-guided group of men (23.8%). Sensitivity and specificity to detect prostate cancer in 1 386 prostate sectors was 53.5% and 70.5% for real-time elastography vs. 11.7% and 93.7% for grey-scale ultrasound, respectively.Compared to conventional grey-scale ultrasound, accuracy to detect prostate cancer using a systematic 10-core biopsy approach was significantly improved under the guidance of real-time elastography.


Referring wisely: orthopedic referral guidelines at an academic institution.
To develop local orthopedic guidelines for use in referral decision support and electronic consultation programs at University of California, San Francisco Health. Modified Delphi method. We performed a 2-phase modified Delphi study to identify consensus between primary care and orthopedic clinicians for common musculoskeletal problems. Clinicians agreed that confirming patient interest in an orthopedic procedure should be completed prior to referral in 81% of clinical scenarios, as well as conservative management in 80%, physical therapy in 60%, and x-ray prior to referral in 42% of scenarios. Clinicians agreed an MRI should not be performed prior to referral in most (58%) clinical scenarios. In the absence of national guidelines, a process for local guideline generation is needed in order to provide nuanced and detailed decision support at the point of referral. The Delphi method proved an effective process to achieve this end.


Type A aortic dissection with transient myocardial ischemia caused by intimal flap inverting into the left ventricle.
A 41-year-old man with sudden onset of chest oppression and downslope ST depression was diagnosed as having type A aortic dissection with angina pectoris and aortic regurgitation. Intraoperative transesophageal echocardiogram (TEE) showed intimal flap inverting into the left ventricle through the aortic valve. This case was rare in that transient myocardial ischemia was induced not by dissection of the aortic root reaching the coronary ostia but by back-and-forth movement of the intimal flap, covering the coronary ostia and interrupting the coronary artery flow. TEE was important for correct diagnosis.


Spectroscopic and quantum chemical study of an alkaloid aristolochic acid I.
Aristolochic acids (AAs) (Aristolochiaceae) are used in the traditional Chinese herb medicine. We have presented the geometry optimization, electrostatic potential surface, frontier orbital energy gap and vibrational wavenumbers of aristolochic acid I (AA I) using ab initio Hartree-Fock (HF) and density functional theory (DFT/B3LYP) method employing 6-311G(d,p) basis set. A complete vibrational assignment has been done on the basis of calculations on monomer and dimer of AA I. The UV-vis absorption spectrum has been recorded in ethanol solvent and compared with the calculated one in the gas phase as well as in solvent environment (integral-equation formalism polarizable continuum model; IEF-PCM) using TD-DFT/6-31G basis set. A short outline of the NBO analysis segment with their structural meaning has been presented. The variation of thermodynamic properties with temperature was calculated theoretically and the thermal response of the compound has been recorded with the help of differential scanning calorimetry (DSC) in N2 environment.


Elucidation of one step synthesis of PEGylated CuFe bimetallic nanoparticles. Antimicrobial activity of CuFe@PEG vs Cu@PEG.
There is a growing field of research on the physicochemical properties of bimetallic nanoparticles (BMNPs) and their potential use in different applications. Meanwhile, their antimicrobial activity is scarcely reported, although BMNPs can potentially achieve unique chemical transformations and synergetic effects can be presented. Towards this direction a reproducible simple hybrid polyol process under moderate temperature solvothermal conditions has been applied for the isolation of non-oxide contaminated bimetallic CuFe nanoparticles (NPs). 1,2-propylene glycol (PG), tetraethylene glycol (TEG) and polyethylene glycol (PEG 8000), that exhibit different physicochemical properties, have been utilized to regulate the size, structure, composition and the surface chemistry of NPs. The BMNPs were found to be of small crystalline size, 30-45nm, and high hydrophilicity, different wt% percentage of organic coating and variable hydrodynamic size and surface charge. The antimicrobial activity of the BMNPs was evaluated against the bacterial strains B. subtilis, E. coli and fungus S. cerevisiae. The IC50 values for CuFe NPs were found significantly lower compared with Cu NPs of the same size, revealing an enhancement in the antimicrobial activity when iron and copper coexist in the crystal structure. The reactive oxygen species (ROS) production was measured intracellularly and extracellularly by the nitroblue tetrazolium assay in the fungal cultures. No extracellular ROS were measured suggesting that both CuFe and Cu NPs enter the fungal cells during the incubation, also verified by optical imaging of the fungal cells in the presence of NPs. Higher ROS concentrations were generated intracellularly for CuFe NPs supporting different red/ox reaction mechanisms.


Brain Meningiomas Manifesting as Intracranial Hemorrhage: Comprehensive Systematic Review and Report of the First Case of Hemorrhagic Meningiomatosis.
To characterize the salient features of hemorrhagic manifestation of meningiomas and to report on the first case of hemorrhagic meningiomatosis. A comprehensive systematic review of the English-language literature was performed using MEDLINE, PubMed, and Google Scholar databases to identify case reports and series of brain meningiomas manifesting as intracranial hemorrhage. A total of 65 patients were evaluated. Most patients were female (64.6%). The average age at presentation was 58.1 ± 14.3 years. The most common presenting symptom was focal neurologic deficits (n = 47; 71.2%). Identification of tumor was missed/not possible in 24.6% of patients. The most common reported comorbidity was hypertension. Most tumors were located in convexity (n = 36; 55.3%). Subdural hematoma (± other hemorrhages) was the most common type of intracranial hemorrhage (n = 46; 70.7%). Computed tomography hyperintensity (25.7%) and magnetic resonance imaging T2 hypointensity (22%) were the most prevalent radiologic findings. The predominant histopathology subtype was meningothelial (syncytial) (n = 24; 36.4%). The estimated mortality was 13.8%. Among those who survived, 39.9% had residual deficits at a median follow-up of 8.1 ± 5.8 months. Intracranial hemorrhage induced by meningiomas is associated with significant mortality and morbidity. Identifying unexpected meningioma in the setting of intracranial bleed can help optimize preoperative planning (e.g., surgical approach) and facilitate total resection of the underlying tumor. Therefore, clinicians should have a high index of suspicion with a low threshold for investigation of meningiomas in the setting of intracranial hemorrhage.


Comparative studies of the haemagglutination of adult and umbilical cord erythrocytes by animal lectins.
1. The sugar specificities of four lactose-binding lectins were studied through the agglutination of adult and/or umbilical cord human erythrocytes (AHRBC and/or CHRBC). 2. Rana catesbeiana egg lectin specifically agglutinated both intact blood group A-AHRBC and intact blood group A-CHRBC. 3. Rana catesbeiana liver lectin agglutinated intact A-AHRBC much more strongly than intact A-CHRBC. 4. Xenopus laevis skin lectin nonspecifically agglutinated AHRBC and CHRBC. 5. Plecoglossus altivelis egg lectin specifically agglutinated intact B-AHRBC, but weakly agglutinated intact B-CHRBC. 6. Comparative studies of lectin-induced AHRBC or CHRBC agglutination clarified the sugar-binding specificities of these lectins.


Septic arthritis of a lumbar facet joint and a sternoclavicular joint.
This is a case report. To the authors' knowledge, simultaneous septic arthritis of a lumbar facet joint and another joint has not been described as yet. Therefore, a patient is presented in whom both a lumbar facet joint (L4-L5 on the right) and a sternoclavicular joint were involved. Septic arthritis of a lumbar facet joint is a rare condition, and only a few cases have been reported in the literature. The etiology, clinical presentation, technical examinations, and treatment are reviewed. Antibiotic treatment was sufficient to heal these lesions. Antibiotic treatment was sufficient to heal these lesions.


Sedation in the neurologic intensive care unit.
Providing adequate sedation in the neurologic intensive care unit (ICU) depends on determination of proper goals for sedation, adequate assessment of the level of sedation, and appropriate choice of drug based on the patient's physiology. The management of sedation in the ICU will influence long-term outcome. Delirium, anxiety, and pain must be identified and treated separately. The use of protocols can improve compliance with published evidence-based recommendations. Propofol and dexmedetomidine may be used for rapidly titratable sedation, benzodiazepines for anxiolysis, neuroleptics for treatment of delirium, and opiates for analgesia. Unique aspects of patients with acute brain disease, such as elevated intracranial pressure or status epilepticus, require adaptation of sedative regimens. Processed EEG monitoring and volatile anesthetic agents have not yet proven beneficial or practical for use in the ICU.


High-dimensional mass cytometry analysis revealed microenvironment complexity in chronic lymphocytic leukemia.
In this study, we extensively dissected the phenotypic complexity of the splenic tumor microenvironment (TME) in chronic lymphocytic leukemia (CLL) by high-dimensional mass cytometry (CyTOF). As a result, we identified potential new targets and tested a dual immune checkpoint blockade targeting the TME in pre-clinical mouse models of CLL.


Inhibition of the metabolism of brotizolam by erythromycin in humans: in vivo evidence for the involvement of CYP3A4 in brotizolam metabolism.
To obtain in vivo evidence for the involvement of cytochrome P450 (CYP) 3A4 in the metabolism of brotizolam. Fourteen healthy male volunteers received erythromycin 1200 mg day(-1) or placebo for 7 days in a double-blind randomized crossover manner. On the 6th day they received a single oral 0.5-mg dose of brotizolam, and blood samplings were performed for 24 h. Erythromycin treatment significantly increased the peak plasma concentration (P < 0.05), total area under the plasma concentration-time curve (P < 0.01), and elimination half-life (P < 0.01) of brotizolam. The present study provides in vivo evidence for the involvement of CYP3A4 in brotizolam metabolism.


Toxicity of nanoplastics to aquatic organisms: Genotoxicity, cytotoxicity, individual level and beyond individual level.
Due to the small size, high mobility and large surface area, nanoplastics (NPs) showed high potential risks to aquatic organisms. This paper reviews the toxicity of NPs to aquatic organism at various trophic levels including bacteria, plankton (algae), zooplankton, benthos, and nekton (fish). The effects at individual level caused by NPs were explained and proved by cytotoxicity and genotoxicity, and the toxicity of NPs beyond individual level was also illustrated. The toxicity of NPs is determined by the size, dosage, and surface property of NPs, as well as environmental factors, the presence of co-contaminants and the sensitivity of tested organisms. Furthermore, the joint effects of NPs with other commonly detected pollutants such as organic pollutants, metals, and nanoparticles etc. were summarized. In order to reflect the toxicity of NPs in the real natural environment, studies on toxicity assessment of NPs with the coexistence of various environmental factors and contaminants, particularly under the concentrations in natural environment are suggested.


Analysis of local qualitative cancer patient experience alongside the 2019 results of the UK National Cancer Patient Experience Survey.
This study analyses data from local qualitative interviewing about what matters most to patients with information from the National Cancer Patient Experience Survey (NCPES) to formulate an accurate improvement plan. This study seeks to provide a deeper analysis of the results of the 2019 NCPES. Qualitative data were collected through a focus group, telephone and virtual interviews from patients in North East London. Ten questions from the NCPES were asked. Interviews were recorded, transcribed verbatim and analysed using an NVivo framework matrix. The results were analysed considering the 2019 National Cancer Patient Experience report. In total, 17 patients and 4 carers participated. The interview answers provided a more in-depth response when compared with the NCPES results, allowing for a deeper understanding of patient experience. This provided an insightful understanding of what matters most to our patients. The NCPES results are not always reflective of the patient population. Limitations of the survey make it hard for healthcare providers to develop accurate improvement plans. It is important to use other data sources such as qualitative interviewing alongside the NCPES. The data collated during this study have been used to identify themes and deliverables for achievable and sustainable improvements to be made.


Effect of dorsal periaqueductal grey lesion on baroreflex and cardiovascular response to air-jet stress.
Certain areas within the periaqueductal grey (PAG) have been implicated in cardiovascular regulation. The influence of excitotoxic lesions of the caudal dorsal periaqueductal grey on the baroreceptor-heart rate reflex and the cardiovascular response to air-jet stress was examined in awake Wistar-Kyoto rats. Pressor (11 +/- 2 mmHg) and tachycardic (25 +/- 4 beats/min) responses to air-jet were not influenced by the lesion. Similarly, the resting MAP and HR were unchanged. However, the gain of the baroreflex was reduced from -3.9 +/- 0.1 to -2.8 +/- 0.3 beats/min per mmHg and the upper threshold was increased from 120 +/- 5 to 135 +/- 7 mmHg in the lesioned group. These observations suggest that although the caudal dorsal PAG does not appear to exert a tonic influence on vasomotor tone or mediate the air-jet response, it may provide a facilitatory input to the baroreceptor-heart rate reflex.


Media experiences during the Ukraine war and their relationships with distress, anxiety, and resilience.
This study investigates the relationships between perceiving media as a positive or negative influence (both news media and fictional media) during the war in Ukraine in 2022 and anxiety, distress, and resilience. Corroborating existing research, our study (N = 393, 47.3% male) showed that there was a clear relationship between the perceived negative impact of both news and fictional media during the war and increased symptoms of anxiety (b = .09, SE = 0.04, p = .024; b = 0.16, SE = 0.04, p < .001, respectively) and distress (b = 0.08, SE = 0.04, p = .047; b = 0.17, SE = 0.04, p < .001, respectively) as well as lowered psychological resilience (b = -0.10, SE = 0.05, p = .047; b = -0.15, SE = 0.06, p = .009, respectively). The study is the first to demonstrate this association for fictional media. Contrary to expectations, however, the perception of a positive impact of both news and fiction was not associated with decreased symptoms of anxiety and distress or higher resilience.


Smart Health Caring Home: A Systematic Review of Smart Home Care for Elders and Chronic Disease Patients.
As access to health care is important to people's health especially for vulnerable groups that need nursing for a long period of time, new studies in the human sciences argue that the health of the population depend less on the quality of the health care, or on the amount of spending that goes into health care, and more heavily on the quality of everyday life. Smart home applications are designed to "sense" and monitor the health conditions of its residents through the use of a wide range of technological components (motion sensors, video cameras, wearable devices etc.), and web-based services that support their wish to stay at home. In this work, we provide a review of the main technological, psychosocial/ethical and economic challenges that the implementation of a Smart Health Caring Home raises.


Creep and friction of ice.
The creep of polycrystalline ice in uniaxial compression has been studied over a very wide range of strain rates. The creep is far too slow to explain the friction of ice observed at very low sliding speeds, but experiments with single crystals show that sliding produces recrystallization at the interface, the ice presenting an orientation favourable to easy glide in directions tangential to the interface.


Arctigenin antagonizes mineralocorticoid receptor to inhibit the transcription of Na/K-ATPase.
Hypertension is one of the most important risk factors in cardiovascular disease and is the most common chronic disease. Mineralocorticoid receptor (MR) antagonists have been successfully used in clinic for the treatment of hypertension. Our study aims to investigate whether Arctigenin can antagonize MR and inhibit the transcription of Na/K-ATPase. The yeast two-hybrid assay was used to screen natural products and Arctigenin was identified as an MR antagonist. The direct binding of Arctigenin to MR was determined using assays based on surface plasmon resonance, differential scanning calorimetry and fluorescence quenching. Furthermore, results from mammalian one-hybrid and transcriptional activation experiments also confirmed that Arctigenin can potently antagonize MR in cells. We demonstrated that Arctigenin can decrease the level of Na/K-ATPase mRNA by antagonizing MR in HK-2 cells. Our findings show that Arctigenin can effectively decrease Na/K-ATPase transcription; thus highlight its potential as an anti-hypertensive drug lead compound. Our current findings demonstrate that Arctigenin is an antagonist of MR and effectively decreases the Na/K-ATPase 1 gene expression. Our work provides a hint for the drug discovery against cardiovascular disease.


Prevalence of IDH1/2 Mutations in Different Subtypes of Glioma in the North-East Population of Morocco.
Genetic alterations in gliomas have increasing importance for classification purposes. Thus, we are especially interested in studying IDH mutations which may feature potential roles in diagnosis, prognosis and response to treatment. Our aim was to investigate IDH mutations in diffuse glioma patients diagnosed in university hospital centre of Fez in Morocco. IDH1 codon 132 and IDH2 codon 172 were direct-sequenced in 117 diffuse glioma samples diagnosed and treated in University Hospital Hassan II between 2010 and 2014. The R132H IDH1 mutation was identified in 43/117 tumor samples and R172K IDH2 mutation was detected in only one anaplastic oligodendroglioma. IDH mutations were observed in 63.2% of astrocytomas, 73.3% of diffuse oligodendrogliomas and 12.90% of glioblastomas. Our results confirmed other studies published earlier for other populations with some small discrepancies.


Oviposition choices by a pre-dispersal seed predator (Hylemya sp.) : II. A positive association between female choice and fruit set.
Pre-dispersal seed predators must choose proper hosts and flowers on those hosts that have a high probability of setting seed. In this study, I documented that flowers of Ipomopsis aggregata (Polemoniaceae) chosen by a pre-dispersal seed predator (Anthomyiidae: Hylemya sp.) had a higher probability of seed set than flowers the fly did not choose. I experimentally tested the hypothesis that Hylemya uses a post-fertilization cue in making oviposition choices. I found no evidence for this hypothesis.


Pediatric Odontogenic Tumors.
Pediatric odontogenic tumors are rare, and are often associated with impacted teeth. Although they can develop anywhere in the jaws, odontogenic tumors mainly occur in the posterior mandible. This article discusses the diagnosis and treatment of the most common pediatric odontogenic tumors, such as ameloblastoma, keratocystic odontogenic tumor, odontoma, and cementoblastoma.


Efficient affinity maturation of antibody variable domains requires co-selection of compensatory mutations to maintain thermodynamic stability.
The ability of antibodies to accumulate affinity-enhancing mutations in their complementarity-determining regions (CDRs) without compromising thermodynamic stability is critical to their natural function. However, it is unclear if affinity mutations in the hypervariable CDRs generally impact antibody stability and to what extent additional compensatory mutations are required to maintain stability during affinity maturation. Here we have experimentally and computationally evaluated the functional contributions of mutations acquired by a human variable (VH) domain that was evolved using strong selections for enhanced stability and affinity for the Alzheimer's Aβ42 peptide. Interestingly, half of the key affinity mutations in the CDRs were destabilizing. Moreover, the destabilizing effects of these mutations were compensated for by a subset of the affinity mutations that were also stabilizing. Our findings demonstrate that the accumulation of both affinity and stability mutations is necessary to maintain thermodynamic stability during extensive mutagenesis and affinity maturation in vitro, which is similar to findings for natural antibodies that are subjected to somatic hypermutation in vivo. These findings for diverse antibodies and antibody fragments specific for unrelated antigens suggest that the formation of the antigen-binding site is generally a destabilizing process and that co-enrichment for compensatory mutations is critical for maintaining thermodynamic stability.


The Sun Health Research Institute Brain Donation Program: description and experience, 1987-2007.
The Brain Donation Program at Sun Health Research Institute has been in continual operation since 1987, with over 1000 brains banked. The population studied primarily resides in the retirement communities of northwest metropolitan Phoenix, Arizona. The Institute is affiliated with Sun Health, a nonprofit community-owned and operated health care provider. Subjects are enrolled prospectively to allow standardized clinical assessments during life. Funding comes primarily from competitive grants. The Program has made short postmortem brain retrieval a priority, with a 2.75-h median postmortem interval for the entire collection. This maximizes the utility of the resource for molecular studies; frozen tissue from approximately 82% of all cases is suitable for RNA studies. Studies performed in-house have shown that, even with very short postmortem intervals, increasing delays in brain retrieval adversely affect RNA integrity and that cerebrospinal fluid pH increases with postmortem interval but does not predict tissue viability.


Correction to: Sucrose isomers as alternative sweeteners: properties, production, and applications.
There is an error in the original publication of this paper. Figures 1 and 2 have been interchanged. The corrected version of these figures is shown below.


Ectopic extra-cranial meningioma presenting as an aural polyp.
Ectopic meningiomas located within the external auditory canal without any intracranial connection are an extremely rare finding. A report is made of a 38-year-old woman presenting with a conductive hearing loss due to an aural polyp, which was subsequently diagnosed as a meningioma. Computer-aided tomography (CT) and magnetic resonance imaging (MRI) showed the tumour to be entirely extracranial. Complete tumour excision was achieved using a modified radical mastoidectomy approach.


Discovery of 2-aminobuta-1,3-enynes in asymmetric organocascade catalysis: construction of drug-like spirocyclic cyclohexanes having five to six contiguous stereocenters.
We present herein for the first time the asymmetric synthesis of drug-like spiranes through reflexive-Michael reaction by using 2-aminobuta-1,3-enyne catalysis under mild conditions.


Correlates of first-episode polarity in a French cohort of 1089 bipolar I disorder patients: role of temperaments and triggering events.
As only a few studies so far systematically reported on bipolar patients subtyped according to first-episode polarity, we took the opportunity of having at disposal a large sample of bipolar I patients to specify the characteristics of patients included in these subtypes, with a special focus on temperament and triggering events. A total of 1089 consecutive DSM-IV bipolar I manic inpatients were subtyped in manic onset (MO), depressive onset (DO) and mixed onset (MXO), and assessed for demographic, illness course, clinical, psychometric, comorbidity and temperament characteristics. The main characteristics of MO patients were a hyperthymic temperamental predisposition, a first episode triggered by substance abuse and an illness course with pure, severe and psychotic mania. In comparison, DO patients had more depressive temperaments, a first episode triggered by stress and alcohol, an illness course with more episodes, cyclicity, suicide attempts, anxious comorbidity and residual symptoms. Although sharing characteristics with either MO or DO, MXO patients had more mixed episodes and cyclothymic temperament. The following are the limitations of this study: retrospective design, bias toward preferential enrolment of MO patients, and lack of information on the number and polarity of lifetime episodes. Findings from this study tend to confirm most of the differences previously evidenced among patients subtyped according to first-episode polarity. Differences found in temperamental predisposition and illness onset triggering events are worth noting and may help target early preventive interventions as well as orientate the search for specific genetic risk factors.


Reduction of energy metabolism in rat hippocampus by arginine administration.
Hyperargininemia is an inherited metabolic disease biochemically characterized by tissue accumulation of arginine. Mental retardation and other neurological features are common symptoms in hyperargininemic patients. Considering that the underlying mechanisms of brain damage in this disease are poorly established, in this work we investigated the effect of arginine administration to adult Wistar rats on some parameters of energy metabolism (CO(2) production, glucose uptake, lactate release and the activities of succinate dehydrogenase, complexes II and IV of the respiratory chain) in rat hippocampus. The action of L-NAME, an inhibitor of oxide nitric oxide synthase, on the effects produced by arginine was also tested. Sixty-day-old rats were treated with a single intraperitoneal injection of saline (group I, control), arginine (0.8 g/kg) (group II) or arginine (0.8 g/kg) plus L-NAME (2 mg/kg) (group III) and were killed 1 h later. Results showed that arginine administration significantly increased lactate release and diminished CO(2) production, glucose uptake, succinate dehydrogenase and complex II activities. In contrast, complex IV (cytochrome c oxidase) activity was not changed by this amino acid. Furthermore, simultaneous injection of L-NAME prevented some of these effects, except CO(2) production and lactate release. The present data indicate that in vivo arginine administration impairs some parameters of energy metabolism in hippocampus of rats probably through NO formation.


Scanning electron microscopy of the respiratory surfaces of Saccobranchus (= Heteropneustes) fossilis (Bloch).
The gill secondary lamellae are generally covered with epithelial cells whose outer surfaces form numerous microvilli. The surface of the primary lamellae is characterised by microridges. A particular type of surface sculpturing seems to be associated with given cell boundaries. Further evidence for the derivation of the air tube and fans which guard its entrance by modification of the basic gill structure has been obtained from both the gross surface architecture and microstructure of the individual cell surfaces. Secondary lamellae are represented by stubby projections which generally have a biserial arrangement. The outer surfaces of the epithelia overlying the capillaries of these respiratory islets are coated with microvilli as in the secondary lamellae. On the other hand, the relatively smooth-surfaced 'lanes' between groups of respiratory islets have a microridged surface similar to that of the primary gill lamellae. It is suggested that previous estimates of surface area, and consequently diffusing capacities of the air-breathing organ, have been low in view of the increased surface, due to both their gross and microstructure. Estimates for gill surface area may need very little correction as the spaces between the microvilli and microridges are probably filled with mucus under normal conditions.


Is diabetic ketoacidosis a good predictor of 5-year metabolic control in children with newly diagnosed type 1 diabetes?
The study aimed to evaluate whether the presence of DKA at diabetes diagnosis was associated with poorer metabolic control during a 5-year follow-up. The study included children treated due to newly diagnosed T1D complicated with DKA between 2010 and 2014 with a complete 5-year follow-up. In every case we performed individual matching for age, gender and BMI with a person without DKA (nDKA) on recognition. We collected data regarding treatment modality, HbA1C, total daily insulin dose, basal insulin and BMI-SDS. 85 children at the median age of 7.93 years had DKA at diabetes diagnosis. The median pH was 7.19.Continuous subcutaneous insulin infusion (CSII) was used in 87% of participants in each group. No differences in HbA1C level (7,3%vs7,2%;p = .413) were noted after 5 years of disease duration. The severity of ketoacidosis exerted no significant effect on HbA1C. The method of insulin delivery at baseline was significantly associated with HbA1C levels after 5 years of observation, βCSII = - 1.46,95%CI[- 2.01 to - 0.92],p < .001. The presence of DKA at diabetes diagnosis is not associated with deteriorated long-term metabolic control in children using modern technologies. The early implementation of CSII into diabetes treatment may change the effect of DKA and lead to a long-term HbA1C improvement.


COVID-19 Vaccine-Related Axillary and Cervical Lymphadenopathy in Patients with Current or Prior Breast Cancer and Other Malignancies: Cross-Sectional Imaging Findings on MRI, CT, and PET-CT.
Breast radiologists are increasingly seeing patients with axillary adenopathy related to COVID-19 vaccination. Vaccination can cause levels I-III axillary as well as cervical lymphadenopathy. Appropriate management of vaccine-related adenopathy may vary depending on clinical context. In patients with current or past history of malignancy, vaccine-related adenopathy can be indistinguishable from nodal metastasis. This article presents imaging findings of oncology patients with adenopathy seen in the axilla or neck on cross-sectional imaging (breast MRI, CT, or PET-CT) after COVID-19 vaccination. Management approach and rationale is discussed, along with consideration on strategies to minimize false positives in vaccinated cancer patients. Time interval between vaccination and adenopathy seen on breast MRI, CT, or PET-CT is also reported.


Effect of Anatomically Realistic Full-Head Model on Activation of Cortical Neurons in Subdural Cortical Stimulation-A Computational Study.
Electrical brain stimulation (EBS) is an emerging therapy for the treatment of neurological disorders, and computational modeling studies of EBS have been used to determine the optimal parameters for highly cost-effective electrotherapy. Recent notable growth in computing capability has enabled researchers to consider an anatomically realistic head model that represents the full head and complex geometry of the brain rather than the previous simplified partial head model (extruded slab) that represents only the precentral gyrus. In this work, subdural cortical stimulation (SuCS) was found to offer a better understanding of the differential activation of cortical neurons in the anatomically realistic full-head model than in the simplified partial-head models. We observed that layer 3 pyramidal neurons had comparable stimulation thresholds in both head models, while layer 5 pyramidal neurons showed a notable discrepancy between the models; in particular, layer 5 pyramidal neurons demonstrated asymmetry in the thresholds and action potential initiation sites in the anatomically realistic full-head model. Overall, the anatomically realistic full-head model may offer a better understanding of layer 5 pyramidal neuronal responses. Accordingly, the effects of using the realistic full-head model in SuCS are compelling in computational modeling studies, even though this modeling requires substantially more effort.


Influence of silicon on polymerization process during lignin synthesis. Implications for cell wall properties.
Silicon (Si) is considered a beneficial element for plants, mostly accumulating in cell walls, where its location and content are primed by the chemistry and structure of lignin. It is unrevealed how Si interacts with the process of lignin formation in the CWs. We studied, in an in vitro system, the interaction of SiO2 with the peroxidase-catalyzed polymerization of a lignin monomer into the lignin model compound, imitating conditions of the last step of lignin formation. FTIR and fluorescence spectroscopy and microscopy showed that Si is bound to the final polymer, and the structure of the Si-DHP differs from pure DHP. Fluorescence spectroscopy showed that Si does not bind to the monomers, so Si probably inhibits the formation of the larger lignin fragments, as evidenced by HPLC-DAD, by binding to dimmers formed during DHP synthesis. The structural changes of the polymer are related to the changed proportion of the fractions of various MW. The enzyme catalyzing DHP synthesis was not inhibited by Si. HRP activity was increased in presence of Si except for 6 mM Si. This may indicate that the complex formed with Si and short oligomers activates the enzyme, and prevents the formation of the large fragments.


Foxo1 directly regulates the transcription of recombination-activating genes during B cell development.
Regulated expression of the recombinase RAG-1 and RAG-2 proteins is necessary for generating the vast repertoire of antigen receptors essential for adaptive immunity. Here, a retroviral cDNA library screen showed that the stress-regulated protein GADD45a activated transcription of the genes encoding RAG-1 and RAG-2 in transformed pro-B cells by a pathway requiring the transcription factor Foxo1. Foxo1 directly activated transcription of the Rag1-Rag2 locus throughout early B cell development, and a decrease in Foxo1 protein diminished the induction of Rag1 and Rag2 transcription in a model of receptor editing. We also found that transcription of Rag1 and Rag2 was repressed at the pro-B cell and immature B cell stages by the kinase Akt through its 'antagonism' of Foxo1 function. Thus, Foxo1 is a key regulator of Rag1 and Rag2 transcription in primary B cells.


The association of Alagille syndrome and craniosynostosis.
Alagille syndrome is associated with various ocular abnormalities, including pseudopapilledema or optic disk edema due to increased intracranial pressure. Several mechanisms have been proposed to explain the mechanism of intracranial hypertension in Alagille syndrome. Craniosynostosis is an unusual but significant cause of increased intracranial hypertension in Alagille syndrome. It has recently been demonstrated in animal models that Jagged1 gene in which mutations are responsible for Alagille syndrome may also take part in cranial suture formation. We report a child with Alagille syndrome and craniosynostosis who presented with pruritus, elevated liver enzymes, and suspected increased intracranial pressure.


Influence of sociocultural factors on the ovulatory status of polycystic ovary syndrome.
To evaluate the role of social and cultural differences inside the same ethnic group on the ovulatory status of women with polycystic ovary syndrome (PCOS). To correlate social and cultural status with the phenotypic expression (body weight and ovulation) and with androgen and insulin levels of PCOS. University department of medicine. Two hundred and forty-four consecutive PCOS women. All studied patients completed a simple questionnaire to indicate their mean family income and their school education. Ovulation was assessed by measurement of serum progesterone on day 22 of a spontaneous or induced menstrual cycle. Levels of blood testosterone, sex hormone-binding globulin, insulin, and blood glucose were evaluated. In the low to medium income group, 21% of patients had ovulatory PCOS, but the prevalence of the same PCOS phenotype was 43% in patients with high income. In patients with low education, only 12% presented with ovulatory PCOS compared with 47% of the patients with high education status. Mean family income negatively correlated with body mass index, waist circumference, insulin, and insulin resistance. Serum progesterone correlated negatively with insulin and insulin resistance. In an ethnically homogeneous PCOS population, high socioeconomic status was associated with a higher prevalence of the ovulatory phenotype. Differences in ovulatory status between the social classes seem to be related to differences in insulin levels and fat quantity and distribution.


A selective pretreatment method for determination of endogenous active brassinosteroids in plant tissues: double layered solid phase extraction combined with boronate affinity polymer monolith microextraction.
Brassinosteriods (BRs), a group of important phytohormones, have various effects on plant growth and development. However, their physiological functions in plants have not been fully understood to date. Endogenous BRs in plant tissue are extremely low and the elucidation of BRs functions relies on sensitive detection method. Reported methods for the determination of BRs required large amount of plant tissue, tedious pretreatment process, and were lack of selectivity. Therefore, development of a simple and selective method for the sensitive quantification of BRs is highly needed. We established a pretreatment method of BRs in plant tissues by employing double layered solid phase extraction (DL/SPE) combined with boronate affinity polymer monolith microextraction (BA/PMME). After the initial depigmentation with DL/SPE cartridge, BA/PMME was employed to selectively extract BRs from sample matrix. Uniquely, most sample matrix was successfully removed by BA monolith purification. Using this method, BRs was determined by liquid chromatography-mass spectrometry (LC-MS). Endogenous active BRs could be detected in only 1 g fresh weigh (FW) leaves or 0.5 g FW flower tissues. A DL/SPE-BA/PMME pretreatment method for the determination of endogenous brassinosteroids in plant tissues was developed and validated. The proposed method was sensitive and selective. Besides, it may be further developed for the determination of other BRs including their precursors and conjugates.


Differences in visual acuity between the eyes: determination of normal limits in a clinical population.
We determined the difference in visual acuity between the right and left eyes of patients and also determined the maximal level of acuity expected in a group of visually normal individuals. Visual acuity was measured in the right and left eyes of 72 subjects aged from 16 to 67 years using Bailey-Lovie type charts. The chart was read until fewer than three letters were read on a line and acuities were based on each letter correct contributing -0.02 to the overall score. For 12 of these subjects, visual acuity was measured a further four times. Average visual acuities for right and left eyes were -0.137 and -0.126log MAR, respectively. The signed visual acuity difference was normally distributed and had a standard deviation of 0.050log MAR. The mean visual acuity difference for the 12 subjects for whom the measures were repeated was 0.033log MAR (SD of the signed visual acuity difference: 0.049log MAR). We conclude that if a patient has a difference in visual acuity between the two eyes of more than 5 letters on a Bailey-Lovie style chart, further investigation is indicated.


Results from a prospective longitudinal survey of employment and work outcomes in newly diagnosed cancer patients during and after curative-intent chemotherapy: A Wisconsin Oncology Network study.
Postcancer work limitations may affect a substantial proportion of patients and contribute to the "financial toxicity" of cancer treatment. The degree and nature of work limitations and employment outcomes are poorly understood for cancer patients, particularly in the immediate period of transition after active treatment. We prospectively examined employment, work ability, and work limitations during and after treatment. A total of 120 patients receiving curative therapy who were employed prior to their cancer diagnosis and who intended to work during or after end of treatment (EOT) completed surveys at baseline (pretreatment), EOT, and 3, 6, and 12 months after EOT. Surveys included measures of employment, work ability, and work limitations. Descriptive statistics (frequencies, percentages, means with standard deviations) were calculated. A total of 111 participants completed the baseline survey. On average, participants were 48 years of age and were mostly white (95%) and female (82%) with a diagnosis of breast cancer (69%). Full-time employment decreased during therapy (from 88% to 50%) and returned to near prediagnosis levels by 12-month follow-up (78%). Work-related productivity loss due to health was high during treatment. This study is the first to report the effects of curative intent cancer therapy on employment, work ability, and work limitations both during and after treatment. Perceived work ability was generally high overall 12 months after EOT, although a minority reported persistent difficulty. A prospective analysis of factors (eg, job type, education, symptoms) most associated with work limitations is underway to assist in identifying at-risk patients.


Polychlorinated biphenyl residues in deep-sea fish from Mediterranean Sea.
Polychlorinated biphenyls including coplanar congeners were measured in the liver of different species of skates and ghostsharks. The mean concentrations of PCBs in skates (314 ng/g wet wt) were comparable with those in ghostsharks (285 ng/g wet wt). The specific analysis of PCB congeners in skates hepatic tissue revealed a profile dominated by hexa-, penta-, and heptachlorinated congeners followed by trichlorobiphenyls, tetra- and decachlorobiphenyls. A different profile dominated by hexa-, tri-, and pentachlorinated congeners, followed by heptachlorobiphenyl and decachlorobiphenyls was found in ghostsharks liver. The estimated 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents (TEQs) of coplanar PCBs in skates and ghostsharks were 0.48 and 0.33 pg/g wet weight, respectively, with mono-ortho congeners PCB105, 118 and 156 contributing more than 90% to the TEQs.


Construction of a novel port wine stain phantom and measurement of colour by digital imaging and reflectance spectrophotometry.
A novel skin phantom is described that is constructed with quantifiable amounts of skin pigments, as well as a light scattering medium in the form of barium sulphate suspension. The two predominant skin pigments (melanin and haemoglobin) are varied in controlled amounts within the phantoms to simulate skin colour in different situations. The phantoms were devised in order to simulate the changes in skin colour particularly after laser treatment of port wine stains, where superficial cutaneous vascularity is reduced. Preliminary investigations of two techniques for skin colour assessment were subsequently carried out so that their suitability for measuring colour in the skin phantoms could be considered. A specifically designed device was constructed to enable repeatable digital image capture of the phantoms. Further development of this skin phantom may enable comparison of techniques for skin colour assessment.


The oxytocinergic system modulates sadistic context-dependent empathy in humans.
The oxytocinergic system is crucial for sociality and well-being and is associated with empathy. It is suggested that the oxytocinergic system exerts context- and person-dependent effects. We examined how sexual sadistic contexts influenced the effects of the oxytocinergic system on empathic-related behaviors and brain activity in healthy adults. Combining genetic neuroimaging, pharmacological techniques and a psychological paradigm of empathy, we recorded EEG neural responses in female OXTR rs53756 G/G and A/A carriers and measured subjective empathic ratings after intranasal administration of oxytocin/placebo in healthy male adults during the perception of painful facial expressions in sadistic/general social contexts. The results revealed that sadistic contexts modulate oxytocinergic effects on empathy at both behavioral and neural levels. The oxytocinergic system preferentially modulated empathic responses to sadistic contexts. These effects are moderated by individual's trait empathy. Our combined genetic-pharmacological-imaging results provide a neurochemical mechanism for sadistic context-dependent effects of the oxytocinergic system on empathy.


Interaction with Ppil3 leads to the cytoplasmic localization of Apoptin in tumor cells.
Apoptin, a small protein encoded by chicken anemia virus (CAV), induces cell death specifically in cancer cells. In normal cells, Apoptin remains in the cytoplasm; whereas in cancerous cells, it migrates into the nucleus and kills the cell. Cellular localization appears to be crucial. Through a yeast two-hybrid screen, we identified human Peptidyl-prolyl isomerase-like 3 (Ppil3) as one of the Apoptin-associated proteins. Ppil3 could bind Apoptin directly, and held Apoptin in cytoplasm even in tumor cells. We then demonstrated that the nuclearcytoplasmic distribution of Apoptin is related to the expression level of intrinsic Ppil3. Moreover, extrinsic modifying of Ppil3 levels also resulted in nuclearcytoplasmic shuffling of Apoptin. The Apoptin P109A mutant, located between the putative nuclear localization and export signals, could significantly impair the function of Ppil3. Our results suggest a new direction for the localization mechanism study of Apoptin in cells.


Embryos, cancers, and parasites: Potential applications to the study of reproductive biology in view of their similarity as biological phenomena.
At present, there are so many living things on the earth. Most of these organisms have a reproductive strategy called sexual reproduction. Among organisms that reproduce sexually, mammals have an extremely complex and seemingly unnatural method of reproduction, or viviparity. As an approach to understanding the nature of viviparity, the author have tried to outline the common life phenomena of embryos, cancers, and parasites based on the literature to date, with internal parasites as the keyword. Embryo, cancer, and parasite are constituted as a systemic interaction with the host (mother). Based on these facts, the author proposed the hypothesis that in the case of mammals, "the fetus is essentially harmful to the mother", and that the parasitic fetus grows by skillfully evading the mother's foreign body exclusion mechanism. Comparative studies of "embryos", "cancers", and "parasites" as foreign bodies have the potential to produce unexpected discoveries in their respective fields. It is important to consider the evolutionary time axis that the basic structure of our mammalian body arose over 200 million years from the Mesozoic Triassic, the period immediately after the Paleozoic Era, when life on Earth became massively extinct.


[Health problems related to occupational activities].
Statistical data obtained from insurance companies give certainly a good picture of work effects on health in the field of accidents. This is different for occupational diseases, which are more difficult to diagnose and which are recognized on the basis of medicolegal criteria. Statistics do not involve other aspects than diseases, such as discomfort, ergonomical questions, psychophysiological consequences and situations where there is a limited role of occupation. Prevention of work related health problems has to consider these characteristics and needs to be based on risk analysis, a prospective procedure. The advantage of such an approach is the possibility of adjustment to a changing work environment and to new technologies.


Microwave ablation of hepatic tumors with a third generation system: loco‑regional efficacy in a prospective cohort study with intermediate term follow-up.
To evaluate the safety and intermediate-term efficacy of percutaneous microwave ablation (MWA) in primary and secondary liver tumors using a third generation MWA device, under ultrasound guidance. Sixty-two patients (median age 74 years, 73 % males) with 69 liver tumors were enrolled in this prospective observational study. Forty-seven patients (76 %) had hepatocellular carcinoma (HCC) and 15 (24 %) metastases. Median follow-up was 3.6 years. Median tumor diameter at contrast enhanced computed tomography was 23 mm (I-III quartiles, 18 - 31 mm). All procedures were performed percutaneously using a 2.45 GHz generator. Median ablation time was 10 minutes (I-III quartiles, 10 - 14 minutes). A single percutaneous antenna insertion was performed for 56/69 (81 %) of the tumors. Technical success was obtained in all tumors. Primary efficacy at 24 hours was achieved in 68/69 (99 %) tumors. The overall one-year cumulative local tumor progression rate was 15.1 % (95 % CI, 7.7 - 24.8 %) with no significant difference between HCC and metastases (p = 0.26). There was one procedure-related mortality (1.6 %) and one major bleeding (1.6 %). Microwave ablation is a valid option for thermal ablation of HCC and liver metastases with comparable complication rate to other local ablative procedures.


Beyond conventional event-related brain potential (ERP): exploring the time-course of visual emotion processing using topographic and principal component analyses.
Recent technological advances with the scalp EEG methodology allow researchers to record electric fields generated in the human brain using a large number of electrodes or sensors (e.g. 64-256) distributed over the head surface (multi-channel recording). As a consequence, such high-density ERP mapping yields fairly dense ERP data sets that are often hard to analyze comprehensively or to relate straightforwardly to specific cognitive or emotional processes, because of the richness of the recorded signal in both the temporal (millisecond time-resolution) and spatial (multidimensional topographic information) domains. Principal component analyses (PCA) and topographic analyses (combined with distributed source localization algorithms) have been developed and successfully used to deal with this complexity, now offering powerful alternative strategies for data-driven analyses in complement to more traditional ERP analyses based on waveforms and peak measures. In this paper, we first briefly review the basic principles of these approaches, and then describe recent ERP studies that illustrate how they can inform about the precise spatio-temporal dynamic of emotion processing. These studies show that the perception of emotional visual stimuli may produce both quantitative and qualitative changes in the electric field configuration recorded at the scalp level, which are not apparent when using conventional ERP analyses. Additional information gained from these approaches include the identification of a sequence of successive processing stages that may not fully be reflected in ERP waveforms only, and the segregation of multiple or partly overlapping neural events that may be blended within a single ERP waveform. These findings highlight the added value of such alternative analyses when exploring the electrophysiological manifestations of complex and distributed mental functions, as for instance during emotion processing.


Effect of high pressure processing and water activity on pressure resistant spoilage lactic acid bacteria (Latilactobacillus sakei) in a ready-to-eat meat emulsion model.
The main use of High Pressure Processing (HPP) in food processing is microorganism inactivation, and studies demonstrated that the characteristics of matrix and microorganisms can interfere on it. As the behavior of lactic acid bacteria exposed to different water activity (aw) levels in a meat product is still unclear, this study aimed to determine the effect of pressure, time, and aw to inactivate Latilactobacillus sakei, a pressure resistant lactic acid bacteria (LAB) in a meat emulsion model through a response surface methodology. The meat emulsion model was designed with adjusted aw (from 0.940 to 0.960) and was inoculated with a pressure resistant LAB and processed varying pressure (400-600 MPa) and time (180-480 s), following the Central Composite Rotational Design (CCRD). The inactivation of the microorganism ranged from 0.99 to 4.12 UFC/g depending on the applied condition. At studied conditions, according to the best fitting and most significant polynomial equation (R2 of 89.73 %), in a meat emulsion model, aw had no influenced on HPP inactivation on LAB (p > 0.05) and only pressure and holding time had significative impact on it. The results of experimental validation of the mathematical model were satisfactory, confirming the suitability of the model. The information obtained in the present study stands out the matrix, microorganism and process effects at HPP efficiency. The answers obtained support food processors in product development, process optimization and food waste reduction.


ARHGAP9 suppresses the migration and invasion of hepatocellular carcinoma cells through up-regulating FOXJ2/E-cadherin.
Rho GTPase activating protein 9 (ARHGAP9), a member of RhoGAP family, has been identified as a RhoGAP for Cdc42 and Rac1. Here, we aimed to clarify the expression and functional role of ARHGAP9 in hepatocellular carcinoma (HCC). By analyzing TCGA (The Cancer Genome Atlas) LIHC (liver hepatocellular carcinoma) database, we found that ARHGAP9 expression was lower in HCC tissues than in normal liver tissues, and that patients with ARHGAP9 lower expression had a significant shorter overall survival time than those with ARHGAP9 higher expression. Cell counting kit-8 (CCK-8), transwell assays and in vivo experimental lung metastasis assay revealed that ARHGAP9 overexpression could inhibit HCC cell proliferation, migration and invasion, as well as HCC lung metastases. By next-generation RNA-sequencing, we identified that a transcription factor, Forkhead Box J2 (FOXJ2), was significantly induced by ARHGAP9 overexpression in HepG2 cells. Ectopic expression of FOXJ2 in HCC cell lines also exerted inhibitory effects on cell migration and invasion. Moreover, the inhibitory effects of ARHGAP9 on HCC cell migration and invasion was significantly attenuated by FOXJ2 knockdown. Luciferase reporter assay demonstrated that ARHGAP9 enhanced the transcription of E-cadherin (CDH1) via FOXJ2. Chromatin immunoprecipitation (ChIP) assay demonstrated that FOXJ2 modulated the transcription of E-cadherin (CDH1) by directly binding to its promoter. Furthermore, Pearson's correlation analysis indicated that the mRNA levels of ARHGAP9 in HCC tissues were positively correlated with the mRNA levels of FOXJ2 and CDH1. These data clearly show that ARHGAP9/FOXJ2 inhibit cell migration and invasion during HCC development via inducing the transcription of CDH1.


Effect of sodium benzoate and chlorhexidine gluconate on a bio-thermoplastic elastomer made from thermoplastic starch-chitosan blended with epoxidized natural rubber.
Thermoplastic elastomer (TPE) was developed by blending thermoplastic starch (TPS) with rubber. Thermoplastic starch-chitosan (TPSC) was prepared by the solution mixing of cassava starch, chitosan (CTS) and glycerol in acidified water (lactic acid 1 wt%) at 80 °C follow by melt mixing at 130 °C. Sodium benzoate (BEN) and chlorhexidine gluconate (Cl) were added during the solution mixing as additives for antimicrobial properties. TPSC was melt-mixed with epoxidized natural rubber (ENR) (70/30 wt/wt). The tensile strength and elongation at break of the TPSC/ENR increased with the additive content. Elastic recovery was improved by the addition of Cl. A new peak in the FTIR data confirmed the reaction between the reactive functional groups of the CTS and the additives with the epoxy groups of ENR. These reactions and miscibility of the TPSC/ENR/additives blends improved the mechanical properties, elasticity, morphology, and antimicrobial properties of the blends.


The Capabilities of Upper Extremity instrument: reliability and validity of a measure of functional limitation in tetraplegia.
To evaluate the reliability and validity of the Capabilities of Upper Extremity (CUE) instrument, designed to measure upper extremity functional limitations in individuals with tetraplegia. Functional limitations are actions such as reaching or grasping and are a link between the domains of impairment and disability. Survey of people with chronic spinal cord injury. Regional spinal cord injury center. One hundred fifty-four individuals (140 male) with tetraplegia at least 1 year after injury and followed by the center. Mean age was 36.7 years (SD=11.1). Sixty-eight percent were motor complete. The 32-item CUE was administered by telephone interview twice about 2 weeks apart. The motor portion of the Functional Independence Measure (FIM) was collected during the first interview. Upper extremity motor scores and motor levels were obtained from the most recent assessment in the outpatient chart. The instrument was evaluated for internal consistency, reliability, and validity. Exploratory factor analysis was performed to examine scale structure. Homogeneity of the scale was excellent. Cronbach's alpha was .96, and item-total correlations ranged from .49 to .78. Test-retest reliability was high (ICC=.94). All but three items had desired levels of agreement (K > .60). Analysis of variance indicated that the CUE distinguished between motor levels of tetraplegia more than one level apart. The CUE was correlated highly with both motor scores and FIM. Regression analysis indicated that the CUE was better than upper extremity motor scores for predicting FIM scores. The model containing the CUE explained 73% of the variance in FIM and was not enhanced by the addition of motor scores. Factor analysis suggested four potential subscales: arm function (bilateral), right hand function, left hand function, and reaching down. The CUE exhibits good homogeneity, reliability, and validity; further work is needed to determine its sensitivity to change in function.


Actin as a model for the study of nucleocytoplasmic shuttling and nuclear dynamics.
A great number of molecules are constantly being exchanged between the nucleus and the cytoplasm via nuclear pore complexes (NPCs). Importantly, this nucleocytoplasmic trafficking is used to transfer information between the two compartments, thereby permitting the manipulation of critical nuclear processes such as transcription. Constant shuttling of actin is an example of the versatility of this regulatory avenue, as this protein has the capability to drive the transcriptional activity of certain gene sets as well as influence transcription on a global scale. Nuclear import and export are extremely dynamic phenomena and require imaging tools capable of rapid sampling rates for proper quantitative observation. Here we describe live-cell imaging assays based on fluorescence recovery after photobleaching (FRAP) and fluorescence loss in photobleaching (FLIP) for monitoring both import and export of fluorescently labelled molecules. Our assays are performed with GFP-actin, but the same principle is applicable to most proteins shuttling between the nucleus and the cytoplasm. Furthermore, these assays may also expose novel qualities of the intranuclear dynamics of a protein, which can polymerize or partake in complexes, because such behavior is mirrored in the nuclear retention of the protein detectable by both import and export assays.