On the defence strategy of Physa fontinalis (L.), a freshwater pulmonate snail.
Physa fontinalis (L.) gives a characteristic, chemically mediated escape response when stimulated by the majority of British leeches and flatworms. The snail responds rapidly and consistently to contact with all the molluskivorous leeches but also to three species which may be considered harmless. However, no response was given to Erpobdella octoculata, the most abundant and widespread of the harmless leeches. The flatworms generally evoked less strong reactions. The adaptive significance of the pattern of responsiveness is discussed. A weaker shell-shaking response is elicited in conspecifics and it is shown that this 'antisocial' behaviour leads to a relatively spaced-out dispersion pattern. A possible adaptive advantage is the reduction of risk of detection by shell-crushing fish predators, to which the snails are otherwise extremely vulnerable.


Alterations in catecholamine levels and turnover in discrete brain areas after food deprivation.
The present study determined the levels and turnover of norepinephrine (NE), epinephrine (EPI) and dopamine (DA) in discrete brain areas of rats after 48 hr food deprivation. The steady-state levels of NE, EPI and DA in saline-treated food-deprived rats, relative to satiated rats, remained basically unchanged. However, 48 hr deprivation caused a site-selective potentiation, specifically in the hypothalamic paraventricular nucleus, in the depletion of NE after alpha-methyl-p-tyrosine injection (IP, 200 mg/kg), indicating an increase in NE turnover. While changes in EPI turnover could not be demonstrated, an apparent increase in DA turnover was detected in the perifornical lateral hypothalamus and anterior hypothalamic nucleus after deprivation, while decreased DA turnover was seen in the hypothalamic dorsomedial nucleus and caudate nucleus. These results may reflect specific functions of hypothalamic catecholamines in control of food intake.


Cyclic AMP-dependent phosphorylation of the inositol-1,4,5-trisphosphate receptor inhibits Ca2+ release from platelet membranes.
Purified internal platelet membranes were treated with the catalytic subunit of protein kinase A to determine its effect on inositol-1,4,5-trisphosphate (IP3)-mediated Ca2+ release. Release kinetics were monitored using rhod-2, a Ca(2+)-specific fluorophore. Protein kinase A maximally inhibited the rate of IP3-mediated Ca2+ release by approximately 30% at saturating IP3 (10 microM). This inhibition was eliminated by pretreatment with a specific kinase inhibitor peptide. Partial purification of the platelet IP3 receptor showed that both endogenous kinases and added A kinase directly phosphorylate the receptor. Since the IP3 receptor is phosphorylated in the absence of added kinase, the observed inhibition (30%) by protein kinase A does not represent the maximal effect of phosphorylation.


Identification of estrogen receptor alpha gene polymorphisms by SSCP and its effect on reproductive traits in Japanese flounder (Paralichthys olivaceus).
Estrogen receptor (ERalpha) modifies the expression of genes involved in cell growth, proliferation and differentiation through binding to estrogen response elements (EREs) located in a number of gene promoters, so the ERalpha gene is considered as an important factor affecting reproductive endocrinology in Japanese flounder (Paralichthys olivaceus). In this study, twelve single nucleotide polymorphisms (SNPs) within eight CDS exons and 1 kb of 3'-UTR of the ERalpha gene were tested to association with four reproductive traits in a population of 119 Japanese flounder individuals with polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP). The association analysis of SNPs within Japanese flounder ERalpha gene with the reproductive traits was carried out using General Linear Model (GLM) estimation. Results indicated that two SNPs in the exon4 of ERalpha gene, P1 (A803G and C864T), were significantly associated with hepatosomatic index (HSI) (P<0.05) in female Japanese flounder. Other ten SNPs in 3'-UTR associated to serum 17beta-estradiol (E(2)) and HSI showed that P2 (A1982T) was significantly associated with E(2) (P<0.01) and P3 (A2149G, 2181TTACAAG2182 insertion or deletion, T2324G, A2359G and G2391A) was significantly associated with HSI (P<0.05) in female Japanese flounder. However, P2 (A1982T) and P4 (G2256T, T2294C, T2309G and A2333T) had significant effects on E(2) (P<0.05 and P<0.01, respectively) in male Japanese flounder. In addition, there were significant associations between diplotype D1 based on fourteen SNPs and reproductive traits. The genetic effects for HSI (female) or E(2) (male) of diplotype D1 were significantly higher than those of other eight diplotypes (P<0.05), respectively. Our findings implied that P1 of ERalpha gene affecting the reproductive traits could be a potential QTN (quantitative trait nucleotide) which would be useful genetic marker in the selection of some reproductive traits for its in Japanese flounder.


cDNA cloning and sequencing of tarantula hemocyanin subunits.
Tarantula heart cDNA libraries were screened with synthetic oligonucleotide probes deduced from the highly conserved amino acid sequences of the two copper-binding sites, copper A and copper B, found in chelicerate hemocyanins. Positive cDNA clones could be obtained and four different cDNA types were characterized.


Use of metformin and risk of kidney cancer in patients with type 2 diabetes.
The anticancer effect of metformin has been reported in the literature but requires additional confirmation in epidemiologic studies. With respect to kidney cancer scarce data are available. This study investigates whether metformin use in patients with type 2 diabetes mellitus (T2DM) might affect kidney cancer risk. The reimbursement database of the National Health Insurance in Taiwan was used. T2DM patients aged ≥ 40 years and newly treated with either metformin (n=171,753, "ever users of metformin") or other antidiabetic drugs (n=75,499, "never users of metformin") within 1998-2002 were followed for at least 6 months for kidney cancer until 31 December 2009. The treatment effect was estimated by Cox regression using propensity score weighting by inverse probability of treatment weighting approach. Hazard ratios were estimated for ever versus never users, and for tertiles of cumulative duration of metformin therapy. During follow-up, 917 ever users and 824 never users developed kidney cancer, with respective incidence of 80.09 and 190.30 per 100,000 person-years. The hazard ratio (95% confidence intervals) for ever versus never users is 0.279 (0.254-0.307); and is 0.598 (0.535-0.668), 0.279 (0.243-0.321) and 0.104 (0.088-0.124), respectively, for the first, second, and third tertile of cumulative duration of <14.5, 14.5-45.8 and >45.8 months. In subgroup analyses, the lower risk of kidney cancer associated with metformin use is consistently observed in both sexes, and in patients with or without concomitant use of other antidiabetic drugs. Metformin use is associated with a decreased risk of kidney cancer in patients with T2DM.


Classical Biological Control of Invasive Legacy Crop Pests: New Technologies Offer Opportunities to Revisit Old Pest Problems in Perennial Tree Crops.
Advances in scientific disciplines that support classical biological control have provided "new tools" that could have important applications for biocontrol programs for some long-established invasive arthropod pests. We suggest that these previously unavailable tools should be used in biological control programs targeting "legacy pests", even if they have been targets of previously unsuccessful biocontrol projects. Examples of "new tools" include molecular analyses to verify species identities and likely geographic area of origin, climate matching and ecological niche modeling, preservation of natural enemy genetic diversity in quarantine, the use of theory from invasion biology to maximize establishment likelihoods for natural enemies, and improved understanding of the interactions between natural enemy and target pest microbiomes. This review suggests that opportunities exist for revisiting old pest problems and funding research programs using "new tools" for developing biological control programs for "legacy pests" could provide permanent suppression of some seemingly intractable pest problems. As a case study, we use citricola scale, Coccus pseudomagnoliarum, an invasive legacy pest of California citrus, to demonstrate the potential of new tools to support a new classical biological control program targeting this insect.


A new flavanone, reflexin, from Cuscuta reflexa and its selective sensing of nitric oxide.
A new compound, reflexin, 5-hydroxy-7-methoxy-6-(2,3-epoxy-3-methylbutyl)-flavanone, is isolated from the stems of Cuscuta reflexa along with three other known compounds. This new compound has good potential for application especially in the photoactivity of reflexin. It was found to be sensitive to glutathione, forming a fluorescent product that is utilized for sensing nitric oxide (NO). The lowest detection limit of NO analysis was found to be 0.05 micro/M.


[A study of the magnification of mandible pantomography image].
To study the degree of magnification of mandible pantomography image. The pantomography of 50 mandible specimens marked with lead pellets were taken by TROPHY XL-90C. The distances between each markers on film and in specimen were measured. The mean magnification(MM) of mandible pantomography image with TROPHY XL-90C was 1.22. MM of horizontal axle was 1.14. MM of vertical axle was 1.29. MM of horizontal axle was greatest (1.24) in the body of mandible,and lest (1.08) in genion. MM of vertical axle is similar among each regions. MM of vertical axle was greater than that of horizontal axle in all regions. The MM parameters of mandible pantomography image were useful to estimate the size of mandible lesions and provided a basis for dental implant more exactly.


Nigrostriatal dopaminergic activity is increased during exhaustive exercise stress in rats.
Exercise capacity is influenced by both increases and decreases in central dopaminergic activity. To investigate the effects of exercise stress on intracerebral dopamine metabolism, rats were run on a motor driven treadmill at 37 m/min for varying times up to exhaustion at 19.6 +/- 0.6 min. Dopamine, DOPAC, and HVA concentrations in striatum, brain stem, and hypothalamus increased towards exhaustion. 5-HIAA concentrations increased in striatum whereas norepinephrine concentrations decreased in hypothalamus. The results indicate that delayed increases in dopaminergic activity occurs during exercise. These, and other observations indicate that central dopaminergic activity modulates exercise performance.


Interleukin-6 plays a crucial role in the hepatic expression of SOCS3 during acute inflammatory processes in vivo.
Interleukin-6 is mandatory for liver regeneration after injury and for the hepatic expression of acute phase proteins and cytochrome P450 enzymes during inflammation. Due to its crucial contribution to the maintenance of homeostasis IL-6 signaling is tightly controlled. Suppressor of cytokine signaling (SOCS) 3 is a potent IL-6-induced feedback inhibitor terminating IL-6 signal transduction. However, several signaling pathways converge on SOCS3: SOCS3 can be induced by other mediators in vitro, and it does not exclusively inhibit IL-6 signaling. The individual contribution of each cytokine to the induction of SOCS3 in vivo is unknown. Using IL-6-deficient mice we analyzed the role of interleukin-6 for the hepatic SOCS3 expression in response to turpentine and LPS as models of aseptic and bacterial inflammation, respectively. In wild-type animals, turpentine and LPS elicited strong induction of SOCS3. IL-6-deficient mice, by contrast, showed severely impaired SOCS3 expression in response to both stimuli: turpentine failed to induce SOCS3 mRNA; in LPS-induced inflammation, the early inductive response 60min after LPS injection was absent, and the delayed expression of SOCS3 was markedly reduced. The residual delayed SOCS3 expression in IL-6-deficient mice was abolished in IL-6/TNFR-1 knockout mice. Our data strongly argue for a crucial role of IL-6 in the hepatic expression of SOCS3 during acute inflammatory processes in vivo. Although other cytokines are capable of inducing SOCS3 their contribution seems to be minor.


A Facile and Low-Cost Route to Heteroatom Doped Porous Carbon Derived from Broussonetia Papyrifera Bark with Excellent Supercapacitance and CO2 Capture Performance.
In this work, we present a facile and low-cost approach to synthesize heteroatom doped porous carbon via hydrothermal treatment of stem bark of broussonetia papyrifera (BP) as the biomass precursor in diluted sulfuric acid, and following thermal activation by KOH at 800 °C. The morphology, structure and textural property of the prepared porous carbon (PC) are investigated by scanning electron microscopy, transmission electron microscopy, N2 sorption isotherms, and X-ray photoelectron spectroscopy. The porous carbon possesses a high BET surface area of 1759 m(2) g(-1) and an average pore size of 3.11 nm as well as hetero-oxygen (9.09%) and nitrogen (1.7%) doping. Such porous carbon shows outstanding capacitive performances of 416 F g(-1) and 300 F g(-1) in three and two-electrode systems, respectively. As a solid-state adsorbent, the obtained porous carbon has an excellent CO2 adsorption capacity at ambient pressures of up to 6.71 and 4.45 mmol g(-1) at 0 and 25 °C, respectively. The results present one novel precursor-synthesis route for facile large-scale production of high performance porous carbon for a variety of great applications including energy storage and CO2 capture.


Risk of an Adverse Event in Individuals Who Aspirate: A Review of Current Literature on Host Defenses and Individual Differences.
The presence of oropharyngeal dysphagia increases the likelihood of prandial aspiration, and aspiration increases the likelihood of a dysphagia-related pulmonary sequelae such as aspiration pneumonia, acute respiratory distress syndrome, pulmonary fibrosis, and even death. Although these outcomes are unfortunate, it is important to point out that these consequences are not solely determined by the presence of aspiration. The purpose of this tutorial is to provide current information on pulmonary defenses and the variables that increase risk of an adverse outcome in individuals who aspirate. This tutorial reviews the basics of lung defenses and summarizes the literature to make the case that the host is a central theme in dysphagia management. Case studies are employed to highlight the key variables. Based on a literature review, a series of questions are proposed for consideration in dysphagia management. These questions, which take the focus away from the presence of aspiration and toward the associated risks within an individual, are then applied to two case studies. A guiding framework is proposed to encourage clinicians to assess more than the presence of aspiration and consider the individual's ability to cope with the aspirated material. In the presence of aspiration, clinicians are urged to focus on the risk factors that can lead to a negative consequence, identify which factors are modifiable, and determine when a level of risk is acceptable.


Management of breast pain and nodularity.
The management of mastalgia consists of classification into its various patterns: reassurance, drug therapy for severe cases, and, rarely, surgery. Differentiation into cyclical and noncyclical patterns on a simple pain chart is useful for objective assessment of pain severity and for selection of appropriate drug therapy and subsequent monitoring of response. About 85% of new patients will be satisfied with adequate reassurance, but some 15% will have persistent pain and warrant medical treatment. Only a small number of drugs have been adequately tested in controlled trails and have been demonstrated to be more effective than placebo; these are bromocriptine, danazol, evening primrose oil, and tamoxifen. No ideal agent exists and the choice of drug will depend on efficacy, side effects, and cost. Noncyclical pain has a lower response rate compared to cyclical mastalgia, but differentiation of a subgroup with chest wall pain leads to an overall 90% response to treatment by local infiltration with steroid and lignocaine. Newer agents such as LHRH agonists are currently undergoing evaluation in double-blind controlled trials against placebo. The management of nodularity is based on the clinical differentiation of the normal spectrum of physiological change within the breast (ANDI), requiring simple reassurance, from a true dominant breast nodule that will require excision biopsy to exclude malignancy. When pain and lumpiness coexist, some reduction in overall nodularity (with the use of agents given for mastalgia) may occur.


Detection and evaluation of volatile and non-volatile antifungal compounds produced by Bacillus spp. strains.
The identification of antifungal compounds produced by microorganisms is crucial in the context of sustainable agriculture. Bacteria of the genus Bacillus have a broad spectrum of action that can influence plant growth and control pests, vectors of public health relevance and phytopathogens. Lipopeptides are the main compounds related to the biological control of several pathogen species. Strains with biotechnological potential are identified by means of in vitro bioassays and molecular tests. In this study, strains from the Bacillus Bank of Brazilian Agricultural Research Corporation (EMBRAPA/DF/Brazil) were selected to control the fungal pathogens Sclerotinia sclerotiorum and Fusarium oxysporum by pairing assays. The detection of genes for biosynthesis of antifungal compounds from strains with high pathogen-inhibition capacity was correlated with peptide synthesis, such as bacillomycin D, fengycin d, bacilysin and surfactin. Their gene expression in contact with the pathogen was analyzed by Real-Time PCR. The volatile organic compounds produced by selected Bacillus strains were identified and quantified. In co-culture assays, the inhibition zone between Bacillus strains and Sclerotinia sclerotiorum was evaluated by scanning electron microscopy. Thirteen potentially anti-pathogenic strains were selected. Genes related to the synthesis of antifungal peptides were detected in 11 of them. In five strains, all tested genes were detected. Bacillomycin was the most frequently found lipopeptide gene. The fungus-bacteria interaction potentiated the production of volatiles. Several ketones and other volatile compounds with antifungal activity were identified. Relevant morphological changes in the fungus were observed when paired with bacteria. The study demonstrated the efficacy of the selected strains with regard to the biological control of phytopathogens and their biotechnological potential.


[Linkage analysis of X-linked nuclear protein gene in Smith-Fineman-Myers syndrome].
To determine the linkage between Smith-Fineman-Myers syndrome (SFMS) and X-linked nuclear protein(XNP) locus. Polymerase chain reaction and denaturing polyacrylamide gel electrophoresis were used to genotype two polymorphic short tandem repeats within XNP gene. One of the two short tandem repeats was informative in SFMS family from Shandong, China. Recombination between SFMS locus and XNP gene was observed in the SFMS family. XNP gene is not associated with the disease in the SFMS family from Shandong, China. SFMS exhibits locus heterogeneity at molecular level.


[Preparation of a staphylococcal immunosorbent sensitized by antibodies to the M-subunit of LDH].
A simple and rapid immunochemical procedure is developed for estimation of the LDH1 activity which involved separation of LDH1 from other LDH isoenzymes using immunosorbent. The immunosorbent consisted of killed Staphylococcus aureus cells, membrane of which contained protein A with absorbed antibodies towards M-subunits of porcine LDH.


A Role for Maternal Factors in Suppressing Cytoplasmic Incompatibility.
Wolbachia are maternally transmitted bacterial endosymbionts, carried by approximately half of all insect species. Wolbachia prevalence in nature stems from manipulation of host reproduction to favor the success of infected females. The best known reproductive modification induced by Wolbachia is referred to as sperm-egg Cytoplasmic Incompatibility (CI). In CI, the sperm of Wolbachia-infected males cause embryonic lethality, attributed to paternal chromatin segregation defects during early mitotic divisions. Remarkably, the embryos of Wolbachia-infected females "rescue" CI lethality, yielding egg hatch rates equivalent to uninfected female crosses. Several models have been discussed as the basis for Rescue, and functional evidence indicates a major contribution by Wolbachia CI factors. A role for host contributions to Rescue remains largely untested. In this study, we used a chemical feeding approach to test for CI suppression capabilities by Drosophila simulans. We found that uninfected females exhibited significantly higher CI egg hatch rates in response to seven chemical treatments that affect DNA integrity, cell cycle control, and protein turnover. Three of these treatments suppressed CI induced by endogenous wRi Wolbachia, as well as an ectopic wMel Wolbachia infection. The results implicate DNA integrity as a focal aspect of CI suppression for different Wolbachia strains. The framework presented here, applied to diverse CI models, will further enrich our understanding of host reproductive manipulation by insect endosymbionts.


PDR16 and PDR17, two homologous genes of Saccharomyces cerevisiae, affect lipid biosynthesis and resistance to multiple drugs.
The Saccharomyces cerevisiae open reading frame YNL231C was recently found to be controlled by the multiple drug resistance regulator Pdr1p. Here we characterize YNL231C (PDR16) and its homologue YNL264C (PDR17). Deletion of PDR16 resulted in hypersensitivity of yeast to azole inhibitors of ergosterol biosynthesis. While no increase in drug sensitivity was found upon deletion of PDR17 alone, a Deltapdr16,Deltapdr17 double mutant was hypersensitive to a broad range of drugs. Both mutations caused significant changes of the lipid composition of plasma membrane and total cell extracts. Deletion of PDR16 had pronounced effects on the sterol composition, whereas PDR17 deletion mainly affected the phospholipid composition. Thus, Pdr16p and Pdr17p may regulate yeast lipid synthesis like their distant homologue, Sec14p. The azole sensitivity of the PDR16-deleted strain may be the result of imbalanced ergosterol synthesis. Impaired plasma membrane barrier function resulting from a change in the lipid composition appears to cause the increased drug sensitivity of the double mutant strain Deltapdr16,Deltapdr17. The uptake rate of rhodamine-6-G into de-energized cells was shown to be almost 2-fold increased in a Deltapdr16,Deltapdr17 strain as compared with wild-type and Deltapdr5 strains. Collectively, our results indicate that PDR16 and PDR17 control levels of various lipids in various compartments of the cell and thereby provide a mechanism for multidrug resistance unrecognized so far.


Lithium Niobate Piezoelectric Micromachined Ultrasonic Transducers for high data-rate intrabody communication.
In recent years, there has been an increased interest in continuous monitoring of patients and their Implanted Medical Devices (IMDs) with different wireless technologies such as ultrasounds. This paper demonstrates a high data-rate intrabody communication link based on Lithium Niobate (LN) Piezoelectric Micromachined Ultrasonic Transducers (pMUTs). The properties of the LN allow to activate multiple flexural mode of vibration with only top electrodes. When operating in materials like the human tissue, these modes are merging and forming a large communication bandwidth. Such large bandwidth, up to 400 kHz, allows for a high-data rate communication link for IMDs. Here we demonstrate a full communication link in a tissue phantom with a fabricated LN pMUT array of 225 elements with an area of just 3 by 3 mm square, showing data-rates up to 800 kbits/s, starting from 3.5 cm and going up to 13.5 cm, which covers the vast majority of IMDs.


A new benzophenone glycoside from the leaves of Mitracarpus villosus.
A new benzophenone glycoside, mitraphenone A (1), together with three known compounds (2-4) were isolated from the leaves of the traditionally used medicinal plant Mitracarpus villosus (Rubiaceae) collected in Nigeria. A combination of one- and two-dimensional NMR spectroscopic and mass spectrometric measurements were carried out to identify the structure of 1. All isolated compounds (1-4) were screened for their antibacterial activity against several Gram-positive and Gram-negative bacteria. Compound 1 exhibited moderate activity against Enterococcus faecium (strains ATCC 35667 and ATCC 700221) and Staphylococcus aureus ATCC 25923 with MIC values ranging from 25 to 50 μM.


Karyological difference between Sagittarius and Cariama (Aves).
Chromosome studies of 1 species of Cariamidae and Sagittarius show great karyological differences and tend to dispel the suggestion of a possible relationship between the families.


Low complication rate and an increasing incidence of surgical repair of primary indirect sliding inguinal hernia.
The purpose of the present study was to explore the risk for complications and reoperations following open repairs for sliding groin hernias. All primary indirect inguinal hernia repairs registered in the Swedish Hernia Register 1998-2011 were identified. Repeated and bilateral procedures were excluded. The epidemiology, the incidence of per- and postoperative complications, and the reoperation rate due to recurrences were analyzed. 100 240 non-repeated unilateral repairs were registered with sliding hernias in 13 132 (13.1 %) (male 14 %, female 5 %) procedures. The methods of repair for sliding and non-sliding hernias were Lichtenstein and other open anterior mesh repairs (N = 10865, 82.7 % and N = 60790, 69.8 %), endoscopic techniques (N = 136, 1.0 % and N = 4352, 5.0 %), and other techniques (N = 2131, 16.2 % and N = 21966, 25.2 %). In multivariate analyses with adjustment for gender, acute/planned surgery, reducibility, method of repair and age, sliding hernias were associated with a low but slightly increased risk for perioperative complications (hazard ratio 1.30, 95 % confidence interval 1.04-1.62, p = 0.023) and postoperative hematoma (hazard ratio 1.13, confidence interval 1.02-1.26, p = 0.019). There was no increased risk of reoperation due to recurrences. Compared to older reports, the incidence of repairs due to primary indirect sliding inguinal hernias has increased over time and it is not just a male disease. The overall results are good with low and comparable complication rates, and no increased risk of reoperations due to recurrences.


A key interaction between the alphavirus envelope proteins responsible for initial dimer dissociation during fusion.
Alphaviruses such as Semliki Forest virus (SFV) are enveloped viruses whose surface is covered by an organized lattice composed of trimers of E2-E1 heterodimers. The E1 envelope protein, a class II fusion protein, contains the hydrophobic fusion loop and refolds to drive virus fusion with the endosome membrane. The E2 protein is synthesized as a precursor p62, whose processing by furin primes the heterodimer for dissociation during virus entry. Dissociation of the E2-E1 heterodimer is an essential step during low-pH-triggered fusion, while the dissociation of the immature p62-E1 dimer is relatively pH resistant. Previous structural studies described an "acid-sensitive region" in E2 that becomes disordered at low pH. Within this region, the conserved E2 H170 is in position to form a hydrogen bond with the underlying E1 S57. Here we experimentally tested the role of this interaction in regulating dimer dissociation in mature and immature virus. Alanine substitutions of E1 S57 and E2 H170 destabilized the heterodimer and produced a higher pH threshold for exposure of the E1 fusion loop and for fusion of the immature virus. E1 S57K or S57D mutations were lethal and caused transport and assembly defects that were partially abrogated by neutralization of the exocytic pathway. The lethal phenotype of E1 S57K was rescued by second-site mutations at E2 H170/M171. Together, our results define a key role for the E1 S57-E2 H170 interaction in dimer stability and the pH dependence of fusion and provide evidence for stepwise dissociation of the E2-E1 dimer at low pH.


Repeated antitumour antibody therapy in man with suppression of the host response by cyclosporin A.
Antibody targeted therapy of cancer results in anti-antibody production which prevents repeated treatment. Cyclosporin A (CsA) has been used to suppress this response in patients treated with a radiolabelled antibody to carcinoembryonic antigen (CEA). Patients with CEA producing tumours received a minimum of two courses consisting of an injection of radiolabelled antibody and CsA, 24 mg kg-1 day-1, for 6 days; each course was given at 2 week intervals. Two weeks after the completion of the second course the mean human antimouse antibody (HAMA) levels were 3.5 micrograms ml-1 (s.d. 2.7) in 3 patients receiving CsA and 1,998 micrograms ml-1 (s.d. 387) in 3 patients not receiving the drug. Clearance of antitumour antibody was accelerated and tumour localisation absent when HAMA levels exceeded 30 micrograms ml-1. With lower levels of HAMA in the CsA-treated patients, further antitumour antibody accumulated in the tumour after each dose. Further therapy with antitumour antibody and CsA lead to the development of HAMA, but this was less than 25% of the amount in patients not given CsA. In this preliminary study up to 4 times as many doses of antitumour antibody could be usefully given when CsA was used. This increases the potential for effective antibody targeted therapy of cancer.


T cell responses to SARS-CoV-2 in humans and animals.
SARS-CoV-2, the causative agent of COVID-19, first emerged in 2019. Antibody responses against SARS-CoV-2 have been given a lot of attention. However, the armamentarium of humoral and T cells may have differing roles in different viral infections. Though the exact role of T cells in COVID-19 remains to be elucidated, prior experience with human coronavirus has revealed an essential role of T cells in the outcomes of viral infections. Moreover, an increasing body of evidence suggests that T cells might be effective against SARS-CoV-2. This review summarizes the role of T cells in mouse CoV, human pathogenic respiratory CoV in general and SARS-CoV-2 in specific.


CdZnS nanorods with rich sulphur vacancies for highly efficient photocatalytic hydrogen production.
A one-dimensional Cd0.6Zn0.4S nanorod (CZS NR) solid solution with rich sulfur vacancies achieved an excellent photocatalytic hydrogen production activity of 59.3 mmol h-1 g-1 under visible irradiation, which is the highest number observed for CdZnS solid solution nanomaterials to date.


[Association between the use of short-acting bronchodilators and the risk of hospitalization for asthma in a real-life clinical practice population cohort].
To determine the number of short-acting beta-agonists (SABA) canisters dispensed in a pharmacy during one year that is associated with higher asthma hospitalization risk in the same period in patients with active asthma. Multi-centre cross-sectional descriptive design. Primary care, MAJORICA cohort including sociodemographic, clinical and electronic prescription system data coded during clinical practice from 68,578 patients with COPD and asthma in the Balearic Islands. A total of 7,648 patients older than 18 years with active asthma, who got any SABA canister from the pharmacy during the 2014-2015 period were included. COPD patients were excluded. Asthma hospitalization, respiratory medication, tobacco, co-morbidities, age and gender. Mean age 47 years, 38% women, 23.2% active smokers. Seventy-seven patients (1%) were admitted for asthma exacerbation in the study period. Patients who received more than 8 SABA containers per year increased the risk of hospitalization (OR 2.81; 95% CI 1.27-6.24). Severity by therapeutic step and amount of inhaled corticosteroids, as well as heart failure and sleep apnea were also significantly associated with hospitalization. There is a significant association between the risk of hospitalization and the higher number of SABA canisters dispensed from the pharmacy. The number of canisters/year that best defines a higher risk of hospitalization is≥8 and could be used to identify asthma at risk.


Dengue Virus Capsid-Protein Dynamics in Live Infected Cells Studied by Pair Correlation Analysis.
It has become increasingly evident that unveiling the mechanisms of virus entry, assembly, and virion release is fundamental for identifying means for preventing viral spread and controlling viral disease. Due to virus mobility and structural and/or functional heterogeneity among viral particles, high spatiotemporal resolution single-virus/single-particle techniques are required to capture the behavior of viral particles inside infected cells.In this chapter, we present fluorescence imaging analysis methods for studying the mobility of fluorescently labeled dengue virus (DENV) proteins in live infected cells. Some of the most recent Fluorescence Fluctuation Spectroscopy (FFS) methods will be presented and, in particular, the pair Correlation Functions (pCF) approach will be discussed. The pCF method does not require individual molecule isolation, as in a particle-tracking experiment, to capture single viral protein behavior. In this regard, image acquisition is followed by the spatiotemporal cross-correlation function at increasing time delays, yielding a quantitative view of single-particle mobility in intact live infected cells.We provide a general overview and a practical guidance for the implementation of advanced FFS techniques, and the pair Correlation Functions analysis, as quantitative tools to reveal insights into previously unreported DENV mechanisms. We expect this protocol report will serve as an incentive for further applying correlation imaging studies in virology research.


Psychosocial factors implied in the onset and clinical picture of the primary affective disorders.
The present study is aimed to investigate the psychosocial factors acting on the individual, at the onset of depressive and/or manic episodes in primary affective disorders. Attention has been paid to the specific influence on the clinical picture, evolution and implicitly on the therapy of the disease.


Should surveillance for liver cancer be modified in hepatitis C patients after treatment-related cirrhosis regression?
Surveillance of hepatocellular carcinoma (HCC) with abdominal ultrasound (US) is recommended for patients with advanced liver fibrosis because of hepatitis C virus (HCV) infections who achieve a sustained virological response (SVR) to antiviral therapy. HCC, in fact, may still develop following SVR as a consequence of long-standing carcinogenic activity of either HCV or hepatic fibrosis, whereas HCC risk in non-viraemic patients may also be driven by cofactors like alcohol abuse or diabetes. This explains the debate on whether surveillance for HCC should be continued in patients with documented cirrhosis regression following a SVR too. While regression of cirrhosis was documented to occur in a majority of patients with compensated cirrhosis 5 years after an SVR to interferon, it should be noted that this clinical benefit could be the consequence of treating a selected population with well-compensated liver disease who in fact were interferon able. This may not be the case for most real-life patients with advanced cirrhosis receiving direct antivirals, in whom liver fibrosis may have reached a point of no-return thus potentially preventing the recovery of a normal liver architecture following SVR. Both invasive and non-invasive tools have suboptimal diagnostic accuracy for fibrosis regression in non-viraemic patients, and this prompts to follow international societies' recommendation to perform surveillance in patients with advanced liver fibrosis achieving a SVR, independently on liver histology outcome.


Extra small metacentric chromosome identified as i(18p).
A case of a supernumerary metacentric small chromosome, diagnosed at birth, is described. The cytogenetic findings support its identification as i(18p). The clinical development from birth to 12 months is reported, with particular attention given to the psychomotor retardation and to the immunological aspect.


Optimization of specimen preparation of thin cell section for AFM observation.
High resolution imaging of intracellular structures of ultrathin cell section samples is critical to the performance of precise manipulation by atomic force microscopy (AFM). Here, we test the effect of multiple factors during section sample preparation on the quality of the AFM image. These factors include the embedding materials, the annealing process of the specimen block, section thickness, and section side. We found that neither the embedding materials nor the temperature and speed of the annealing process has any effect on AFM image resolution. However, the section thickness and section side significantly affect the surface topography and AFM image resolution. By systematically testing the image quality of both sides of cell sections over a wide range of thickness (40-1000 nm), we found that the best resolution was obtained with upper-side sections approximately 50-100 nm thick. With these samples, we could observe precise structure details of the cell, including its membrane, nucleoli, and other organelles. Similar results were obtained for other cell types, including Tca8113, C6, and ECV-304. In brief, by optimizing the condition of ultrathin cell section preparation, we were able to obtain high resolution intracellular AFM images, which provide an essential basis for further AFM manipulation.


Interdependent Networks: A Data Science Perspective.
Traditionally, networks have been studied in an independent fashion. With the emergence of novel smart city technologies, coupling among networks has been strengthened. To capture the ever-increasing coupling, we explain the notion of interdependent networks, i.e., multi-layered networks with shared decision-making entities, and shared sensing infrastructures with interdisciplinary applications. The main challenge is how to develop data analytics solutions that are capable of enabling interdependent decision making. One of the emerging solutions is agent-based distributed decision making among heterogeneous agents and entities when their decisions are affected by multiple networks. We first provide a big picture of real-world interdependent networks in the context of smart city infrastructures. We then provide an outline of potential challenges and solutions from a data science perspective. We discuss potential hindrances to ensure reliable communication among intelligent agents from different networks. We explore future research directions at the intersection of network science and data science.


Trends in Prescribing Preferences for Antidiabetic Medications Among Patients With Type 2 Diabetes in the U.K. With and Without Chronic Kidney Disease, 2006-2020.
To evaluate trends in antidiabetic medication initiation patterns among patients with type 2 diabetes mellitus (T2DM) with and without chronic kidney disease (CKD). A retrospective cohort study using the UK Clinical Practice Research Datalink (2006-2020) was conducted to evaluate the overall, first-, and second line (after metformin) medication initiation patterns among patients with CKD (n = 38,622) and those without CKD (n = 230,963) who had T2DM. Relative to other glucose-lowering therapies, metformin initiations declined overall but remained the first-line treatment of choice for both patients with and those without CKD. Sodium-glucose cotransporter-2 (SGLT2i) use increased modestly among patients with CKD, but this increase was more pronounced among patients without CKD; by 2020, patients without CKD, compared with patients with CKD, were three (28.5% vs. 9.4%) and six (46.3% vs. 7.9%) times more likely to initiate SGLT2i overall and as second-line therapy, respectively. Glucagon-like peptide 1 receptor agonist (GLP-1RA) use was minimal regardless of CKD status (<5%), whereas both dipeptidyl peptidase-4 inhibitor (DPP4i) and sulfonylurea use remained high among patients with CKD. For instance, by 2020, and among patients with CKD, DPP4i and sulfonylureas constituted 28.3% and 20.6% of all initiations, and 57.4% and 30.3% of second-line initiations, respectively. SGLT2i use increased among patients with T2DM, but this increase was largely driven by patients without CKD. Work is needed to identify barriers associated with the uptake of therapies with proven cardiorenal benefits (e.g., SGLT2i, GLP-1RA) among patients with CKD.


CisPG21 and CisCEL16 are involved in the regulation of the degradation of cell walls during secretory cavity cell programmed cell death in the fruits of Citrus sinensis (L.) Osbeck.
Pectinase and cellulase participate in cell wall degradation during secretory cavity formation in Citrus fruits. However, it remains unknown how secretory cavity formation is regulated by pectinase and cellulase genes in a schizolysigenous model. Our Results showed that PCD was involved in the schizolysigenous formation of the secretory cavities, and pectinase was involved in the degradation of the middle lamella while pectinase combined with cellulase were responsible for the degradation of the primary cell wall. Furthermore, the expression levels of CisPG21 and CisCEL16 at the intercellular space-forming and lumen-expanding stages with the continuous degradation of the cell wall were significantly higher than those at the initial cell stage and mature stage. The in situ hybridization (ISH) results also showed that CisPG21 and CisCEL16 were mainly located in the degrading cells of secretory cavities, and signals were very strong at the intercellular space-forming and lumen-expanding stages. In conclusion, pectinase and cellulase are directly involved in the degradation of PCD cell walls during schizolysigenous formation in the secretary cavity of Citrus sinensis (L.) Osbeck fruit, while CisPG21 and CisCEL16 are important regulatory genes of pectinase and cellulose during cell wall degradation.


Renal osteodystrophy: a pediatric perspective, 2005.
Renal osteodystrophy (ROD) associated with chronic kidney disease (CKD) involves a complex interrelationship of the loss of divalent mineral homeostasis, hyperparathyroidism, and gene modulation. In affected children, ROD leads to impaired linear growth as well as to the development of other significant skeletal and extraskeletal manifestations. Despite the success of kidney transplantation, many ROD complications cannot be completely reversed; and thus, patients with CKD and ROD require long-term follow-up. Although the availability of vitamin D analogues has advanced ROD management, it has also created new issues for clinicians to address, motivating future investigations of calcimimetic therapies. An algorithmic approach to the management of ROD in children is presented; to be most effective, this approach requires close and frequent surveillance to prevent side effects related to potent therapies.


Levetiracetam versus Phenobarbital for Neonatal Seizures: A Retrospective Cohort Study.
Although phenobarbital (PB) is commonly used as a first-line antiseizure medication (ASM) for neonatal seizures, in 2015 we chose to replace it with levetiracetam (LEV), a third-generation ASM. Here, we compared the safety and efficacy of LEV and PB as first-line ASM, considering the years before and after modifying our treatment protocol. We conducted a retrospective cohort study of 108 neonates with electroencephalography (EEG)-confirmed seizures treated with first-line LEV or PB in 2012 to 2020. First-line ASM was LEV in 33 (31%) and PB in 75 (69%) neonates. The etiology included acute symptomatic seizures in 69% of cases (30% hypoxic-ischemic encephalopathy, 32% structural vascular, 6% infectious, otherwise metabolic) and neonatal epilepsy in 22% (5% structural due to brain malformation, 17% genetic). Forty-two of 108 (39%) neonates reached seizure freedom following first-line therapy. Treatment response did not vary by first-line ASM among all neonates, those with acute symptomatic seizures, or those with neonatal-onset epilepsy. Treatment response was lowest for neonates with a higher seizure frequency, particularly for those with status epilepticus versus rare seizures (P < 0.001), irrespective of gestational age, etiology, or EEG findings. Adverse events were noted in 22 neonates treated with PB and in only one treated with LEV (P < 0.001). Our study suggests a potential noninferiority and a more acceptable safety profile for LEV, which may thus be a reasonable option as first-line ASM for neonatal seizures in place of PB. Treatment should be initiated as early as possible since higher seizure frequencies predispose to less favorable responses.


First-line treatment of advanced gastric cancer and hepatic dysfunction with oxaliplatin, 5-fluorouracil and cetuximab.
There is no standard chemotherapy regimen in advanced gastric cancer with poor performance status and hepatic dysfunction. New chemotherapeutical agents and targeted therapy have demonstrated promising results in terms of efficacy and safety in phase II clinical trials. We report the case of a 68-year-old man with stage IV gastric cancer and severe hepatic dysfunction due to liver metastases treated with a combination of oxaliplatin, 5-fluorouracil and cetuximab.


Cholinergic innervation of pig pancreas.
Pancreases from 5 sexually mature sows were used in this investigation. In order to detect cholinergic fibers in the pancreas, the method of Karnovsky and Roots (1964) was applied. It was shown that cholinergic nerve fibers occur in the whole organ as perivascular plexuses, interlobular nerves, perilobular and periinsular plexuses. The existence of individual cholinergic neurons in the pig pancreas also has been stated.


Thromboxane release after reperfusion of chronically ischemic limbs in patients.
We hypothesized that chronic ischemia of peripheral vascular disease would lead to increased thromboxane A2 (TxA2) and decreased prostacyclin (PGI2) production and surgical correction of the ischemia would stabilize TxA2 and PGI2 at normal levels. TxA2 and PGI2 concentrations were determined in 22 patients before, during, and after arterial reconstruction for limb salvage and in 10 control subjects. Control samples and preoperative patient samples had no detectable TxA2 or PGI2 (less than 26 pg/ml). Five minutes after reperfusion TxA2 increased (TxA2 = 76.27 +/- 48.9 pg/ml, mean +/- SEM) and persisted at 1 day (TxA2 = 190.1 +/- 80.1 pg/ml), 2 days (TxA2 = 224.7 +/- 131.7 pg/ml), 5 days (TxA2 = 334.8 +/- 272.8 pg/ml), and 7 days postoperatively (TxA2 = 256.6 +/- 149.0 pg/ml). Elevated TxA2 production was not associated with chronic ischemia of peripheral vascular disease. Reperfusion of the severely ischemic limb caused significant TxA2 release.


Search for basic relationships between "molecular size" and "chemical structure" of aquatic natural organic matter--answers from 13C and 15N CPMAS NMR spectroscopy.
To investigate the structural composition of natural organic matter (NOM), a 3-step micro- and ultrafiltration procedure was applied to 3 surface waters from southern Germany, and fractions from all filtration steps were collected. The NOM was characterized using solid-state 13C and 15N nuclear magnetic resonance (NMR) techniques. Routine integration of the 13C NMR spectra and extended data analysis procedures were carried out for a quantitative comparison of the structural components as well as for the elucidation of structural fractionation patterns. A common feature of the large molecular size fractions was the predominance of polysaccharide material, with the dissolved high molecular weight organics being mostly enriched in N-acetylated polysaccharides derived from microbial leftovers. Aromatic structures like lignin and tannin derivatives were most abundant in the intermediate size fraction. All membranes were found to be highly permeable for branched aliphatics, i.e. isoprenoids. Fouling layers of the ultrafiltration membrane were significantly enriched in long-chain aliphatics (lipids). Biofouling was not observed on any of the membranes. Overall, a strong interdependence between the chemical structural characteristics of NOM components and their size, shape, or interaction characteristics could be shown. The results provide the basis for a better understanding of water process technologies as treatment effectiveness is strongly dependent on the chemical composition and the "size" distribution of NOM.


Farmers' trust in government and participation intention toward rural tourism through TAM: The moderation effect of perceived risk.
At present, there are almost 700 million rural population in China, and the farm and farmers in China are highly associated with the steadiness and development of the country and even the world. Farmers are the main subjects in rural development and play a vital role in the reception, management, and benefit distribution in rural tourism activities during the development of rural tourism. Farmers' perception and participation intention in rural tourism development are directly related to the sustainable development of rural tourism and the realization of rural revitalization goals. The decision-making process of participation in the rural tourism development fits the application conditions of the technology acceptance model (TAM). Therefore, in order to explore the influencing factors of farmers' decision-making process in participating in the rural tourism, this study employs the technology acceptance model to predict and judge individual farmers' willingness and behavior to participate in the rural tourism. The government trust and perceived risk in the real problem of low participation of farmers in the rural tourism development are considered. Then, an extended technology acceptance model was established by taking 409 farm households as research samples. The influence of government trust on farmers' participation intention in the rural tourism was empirically analyzed based on the PLS-SEM model. The results show that farmers' perceived usefulness and perceived ease of use in rural tourism affect their participation intention. Farmers' judgments on whether governments can assume public responsibilities and achieve public interests through rural tourism development affects their trust in government, while the government trust can positively affect farmers' participation intention via perceived usefulness and perceived ease of use. This indicates that government trust is an important antecedent variable influencing farmers' participation in the rural tourism. The perceived risk affects farmers' perceived usefulness and participation intention in the rural tourism, and plays a moderating role in the relationship between government trust and perceived usefulness. Finally, this study recommends to highlight the utility and convenience of rural tourism participation during the promotion of farmers' participation in rural tourism development, enhance the ability of farmers to participate in rural tourism development, and choose multiple channels to increase government trust to reduce farmers' risk concerns.


Five point initiative: a community-informed bundled implementation strategy to address HIV in Black communities.
Black individuals in the U.S. remain the most disproportionately impacted by new HIV diagnoses, represent the highest portion of individuals living with HIV, and have the highest morbidity rates. Structural inequities and historical oppression are the primary drivers. Such drivers limit access to HIV prevention tools that need to be delivered with culturally congruent and community-informed approaches. The Five Point Initiative (FPI) is a community-informed bundled implementation strategy developed and piloted between September 2019 and March 2020 in Miami, Florida in communities heavily impacted by HIV. Key components of the strategy included community consultants/experts, five categories (hence the "Five Point") of community businesses (e.g., corner stores, beauty supply stores, laundromats, mechanics, barbershops), local health organizations, an academic research program engrossed in community engaged research, and community residents who provided ongoing feedback throughout. Outcomes of FPI included (a) survey information (e.g., knowledge of and access to PrEP, barriers to care) and pilot data (acceptability and feasibility), (b) expansion of reach to Black individuals in HIV high impact zip codes in Miami, (c) insights on our bundled implementation strategy, (d) condom distribution, and (e) HIV testing. Over the course of six months FPI carried out 10 outreach events, partnered with 13 community businesses and 5 health organizations, engaged 677 community residents, collected health information via a survey, distributed 12,434 condoms, provided information on PrEP, and offered voluntary HIV testing (131 completed). FPI's ability to reach residents who are not being reached (e.g., 68.8% never heard of PrEP, 8% no HIV testing ever, 65.9% no primary care provider), positive feedback from residents (e.g., 70% very satisfied, 21% satisfied; 62% strongly agree and 25% agree they would participate again) and qualitative interviews with businesses provide evidence of acceptability and feasibility. Further, survey data provided insights on factors such as socio-demographics, discrimination experiences, barriers to care, social-structural factors, physical and sexual health, and mental health and substance use. The FPI bundled implementation strategy shows promise to deliver health prevention/intervention for HIV and other health conditions to communities facing health inequities and for whom the current system for delivering care is insufficient.


Solid-state conformations of aminosuccinyl peptides: crystal structure of tert-butyloxycarbonyl-L-leucyl-L-aminosuccinyl-L-phenylalaninami de.
The protected tripeptide tert-butyloxycarbonyl-L-leucyl-L-aminosuccinyl-L-phenylalaninamide crystallizes in the orthorhombic space group P2(1)2(1)2(1), with a = 6.214(3), b = 12.832(3), c = 33.094(4) A, Z = 4. The structure was solved by direct methods using MULTAN 80 and refined to an R value of 0.055 for 1458 reflections. The bond lengths and angles are in good agreement with the standard values. The peptide backbone adopts a type II' beta-bend conformation with a weak intramolecular hydrogen bond between the CO group of the leucyl residue and the C-terminal NH2 group. In agreement with previous studies, this structure confirms the high propensity of aminosuccinyl peptides to adopt a type II' beta-bend conformation. The role of this conformation in relation to the deamidation process in proteins is also discussed.


NPY suppressed development of experimental autoimmune encephalomyelitis in Dark Agouti rats by disrupting costimulatory molecule interactions.
Neuropeptide Y (NPY) suppressed clinical experimental autoimmune encephalomyelitis (EAE) and reduced numbers of CD28+, CD11b+ and CD80+ cells among spinal cord infiltrating cells at the peak of disease in Dark Agouti rat strain. Suppression of EAE was accompanied by the reduced expression of costimulatory CD80 and CD86 molecules on ED1+ macrophages and OX62+ dendritic cells in draining lymph nodes during the inductive phase of EAE. An inhibitor of dipeptidyl peptidase 4, an enzyme which terminates the action of NPY on Y1 receptor subtype, did not sustain the suppressive effect of NPY on the EAE development, suggesting involvement of Y2 and Y5 receptors.


Angioarchitectural structure and functional distributive pattern of the filiform papillae on the meso-dorsal surface of the rabbit tongue.
The angioarchitectural classification and distributive patterns were investigated in the filiform papillae (FiP) on the meso-dorsal surface of the rabbit tongue by using microvascular cast specimens (MVCS) and the scanning electron microscope (SEM). The author examined the microvascular network structures, which consisted of ascending and descending branches entering the FiP. They inclined in a posterior (pharynx) direction, and densely and geometrically covered the meso-dorsal surface, directing the spoon-like concave face in an anterior direction. FiPs could be classified into three types: a small filiform papilla (SfP) covering on the meso-dorsal surface except for the marginal part of the intermolar eminence (MIME) and the intermolar eminence itself (IME): a spoon-like concave structure facing in an anterior (apex) direction with an arrowhead-like top: a middle filiform papilla (MfP) on the MIME, made up of a long triangle-like concave structure with a sharp arrowhead-like top and inclined at right angles to the IME. A large filiform papilla (LfP) on the whole swelling dorsal area of the IME was formed by a long triangle-like concave structure with a sharper arrowhead-like top. LfPs are longer and larger than MfPs and inclined towards the pharynx.


Evaluation of anatomical consistency in craniofacial superimposition images.
Using 52 skulls in forensic cases, the anatomical consistency of cranio-facial superimposition images was investigated for evaluating the validity in personal identification by the superimposition method. In 35 out of 52 cases the unknown skull was positively identified as the missing person by matching of the outline and anatomical relation in skull and face images taken from frontal, oblique and lateral directions. The unknown skull in two cases was exclusive of the presumed person since the outline of the skull was not anatomically consistent with that of the face. In the remaining 15 cases, the skull in question was examined using only a frontal face photograph of the missing person and matched with it because of the lack of other photographs taken from different angles, giving a probable identification. From our practical examination, it is stated that the outline from the trichion to the gnathion in the lateral or oblique view is the preferable portion for personal identification, and the cranio-facial super-imposition method is reliable for individualization when two or more facial photographs taken from different angles are used in the examination.


Hypermethylation of tumor suppressor genes is a risk factor for poor prognosis in ovarian cancer: A meta-analysis.
DNA methylation is the earliest and most studied epigenetic modification in cancer. The literature reported that the abnormal methylation level of multiple genes was associated with poor prognosis in ovarian cancer. However, due to a small sample size, the results reported in the literature vary widely. In this study, the correlation between aberrant methylation level of genes and poor prognosis of ovarian cancer was reviewed in order to clarify the role of DNA methylation in the prognosis of ovarian cancer. A systematic research of PubMed, EMbase, Cochrane Library, China Biology Medicine disc (CBMdisc), China National Knowledge Infrastructure (CNKI), Wanfang databases, and EMBASE was performed, and calculated the hazard ratio (HR) of overall survival (OS) and progression-free survival (PFS) and its 95% confidence interval. HR of the OS obtained of target genes was 2.32 (95% CI: 1.54-3.48, P = .000); HR of the PFS obtained of target genes was 1.318 (95% CI: 0.848-2.050, P = .220). HR of OS achieved by tumor suppressor genes was 3.09 (95% CI 1.80 - 5.30, P = .000). Hypermethylation of tumor suppressor genes indicate poor prognosis of ovarian cancer.


Developing on-machine 3D profile measurement for deterministic fabrication of aspheric mirrors: erratum.
This erratum adds a reference to the published paper, Appl. Opt.53, 4997 (2014)APOPAI0003-693510.1364/AO.53.004997.


Effects of contextual support on preschoolers' accented speech comprehension.
Young children often hear speech in unfamiliar accents, but relatively little research characterizes their comprehension capacity. The current study tested preschoolers' comprehension of familiar-accented versus unfamiliar-accented speech with varying levels of contextual support from sentence frames (full sentences vs. isolated words) and from visual context (four salient pictured alternatives vs. the absence of salient visual referents). The familiar accent advantage was more robust when visual context was absent, suggesting that previous findings of good accent comprehension in infants and young children may result from ceiling effects in easier tasks (e.g., picture fixation, picture selection) relative to the more difficult tasks often used with older children and adults. In contrast to prior work on mispronunciations, where most errors were novel object responses, children in the current study did not select novel object referents above chance levels. This suggests that some property of accented speech may dissuade children from inferring that an unrecognized familiar-but-accented word has a novel referent. Finally, children showed detectable accent processing difficulty despite presumed incidental community exposure. Results suggest that preschoolers' accented speech comprehension is still developing, consistent with theories of protracted development of speech processing.


Seminal fructose, citric acid and acid phosphatase before and after vasectomy in man.
Seminal fructose, citric acid and acid phosphatase were estimated from 23 healthy males before vasectomy and three months later. Each subject had children and the men volunteered for sterilization because other possibilities of contraception were inapplicable. Vasectomy was performed under local anesthesia in the conventional manner. Semen of all patients was azoospermic three months after vasectomy. In this study, the amounts of seminal fructose and citric acid were significantly higher after vasectomy than before operation. The activity of seminal acid phosphatase was a little less, but the difference was not significant. The increase of seminal fructose and citric acid could be explained by the lack of spermatozoa, which normally use them into their metabolism.


Malignant gastrointestinal neuroectodermal tumor: a case report and review of the literature.
Malignant gastrointestinal neuroectodermal tumor (GNET) is an extremely rare entity that was first described by Zambrano et al. in 2003 as "Clear cell sarcoma-like tumor of the gastrointestinal tract". It shares some of the histological features of clear cell sarcoma (CCS) but lacks the immunohistochemical reactivity for melanocytic markers. We report a case of GNET that was initially misdiagnosed as gastrointestinal stromal tumor (GIST). Recognizing this entity is important to avoid misdiagnosis. A case of an 18-year-old male presented with a small intestinal tumor. Histologically it was characterized by polygonal cells arranged in pseudoalveolar pattern and situated in the muscularis propria. Scattered osteoclast-like multinucleated giant cells were also noted. The neoplastic cells were positive for S-100 protein and negative for HMB-45, Melan A, smooth muscle actin, desmin and CD117. EWSR1 gene rearrangement was detected by fluorescence in situ hybridization (FISH) analysis. The patient returned with recurrence after 36 months' management by surgical resection and died one year later. GNET can be mistaken histologically for other non-epithelial gastrointestinal tumors. Awareness of its existence and diagnostic criteria by the pathologist is necessary to avoid misdiagnosis, particularly as GIST, CCS or malignant peripheral nerve sheath tumor (MPNST).


GeLC-Orbitrap/MS and 2-DE-MALDI-TOF/TOF comparative proteomics analysis of seed cotyledons from the non-orthodox Quercus ilex tree species.
Gel electrophoresis-based and shotgun approaches are the most employed proteomic platforms in plant biology research, with the latter replacing the former in the last years. We have compared 2-DE-MALDI-TOF/TOF and GeLC-Orbitrap/MS analyses using the same protein extracts from Quercus ilex cotyledons at different development stages. The results obtained (ProteomeXchange available data, PXD020603) showed that both platforms were complementary, showing common and specific proteins identified in each case, but leading to similar biological conclusions. Protein analysis identified 562 spots in gel-based (292 variables) and 2409 proteins in shotgun (560 variables), that were detected with both platforms and represent common key pathways related to maturation and germination. The main differences concern hormone metabolism, storage and late embryogenesis abundant proteins. Deeper proteome coverage was obtained with the shotgun approach, with a greater number of metabolic pathways represented, as gibberellin biosynthesis, not observed in the gel-based analysis. Nevertheless, several storage proteins, highly abundant in cotyledons and well represented in gel-based platform were not identified using the shotgun platform. These results support that when analyzing any plant biological process, the use of both platforms is complementary rather than redundant, that favors an in-depth proteomic analysis and a more confident biological interpretation of the data obtained.


Real-World Treatment Patterns After CD19-Directed CAR T Cell Therapy Among Patients with Diffuse Large B Cell Lymphoma.
CD19-directed chimeric antigen receptor T cells (CAR T) are approved for treatment of adults with relapsed/refractory diffuse large B cell lymphoma (DLBCL) following at least two lines of therapy. This study describes real-world treatment patterns after CAR T in adults with DLBCL. It includes adults diagnosed with DLBCL in IBM MarketScan Commercial and Medicare Supplemental healthcare claims databases administered CAR T between 2017 and 2019 (index event) and at least 6 months of continuous health plan enrollment pre-index. Kaplan-Meier methods were used to estimate risk and time to first subsequent treatment after CAR T, as a proxy for CAR T failure. Among 129 patients meeting study criteria, most (123; 95.4%) were hospitalized during CAR T therapy. Median length of stay was 17 (25th-75th percentile, 13-22) days. Estimated 6-month risk of subsequent treatment was 36.2% (95% confidence interval [CI] 27.1-45.8%). During median follow-up of 195 (25th-75th percentile, 102-362) days, median time to the first line of therapy after CAR T, accounting for censoring, was 378 days (95% CI 226, not reached). Among 48 patients who received another therapy after CAR T, 58.3% received immunotherapy, 50.0% radiation therapy, 25.0% chemotherapy, 25.0% targeted therapy, and 12.5% hematopoietic stem cell transplant. Among real-world patients with DLBCL treated with CAR T, the risk of not achieving a durable response is considerable; additional, effective options for DLBCL salvage treatment are needed.


NuMA and nuclear lamins are cleaved during viral infection--inhibition of caspase activity prevents cleavage and rescues HeLa cells from measles virus-induced but not from rhinovirus 1B-induced cell death.
Nuclear matrix is a structural framework of important nuclear processes. We studied the effect of two different types of viral infections on nuclear matrix. HeLa cells were infected with human rhinovirus 1B (HRV 1B) or measles virus (MV), and Nuclear Mitotic Apparatus protein (NuMA) and lamins A/C and B were used as markers for internal nuclear matrix and peripheral nuclear lamina, respectively. We show that NuMA, lamins, and poly(ADP-ribose) polymerase-1 are cleaved during viral infection in a virus family-specific manner suggesting that these viruses activate different sets of proteases. Morphologically, NuMA was excluded from the condensed chromatin, lamins showed a folded distribution, and both proteins finally remained around the nuclear fragments. A general caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD-FMK) prevented the nuclear disintegration and the cleavage of the proteins studied. Interestingly, z-VAD-FMK rescued MV-infected but not HRV 1B-infected cells from cell death. These results show for the first time that NuMA and lamins are specific target proteins during virus-induced programmed cell death.


A Rapid Protocol for Preparing 8-Aminopyrene-1,3,6-Trisulfonate-Labeled Glycans for Capillary Electrophoresis-Based Enzyme Assays.
Purified glycan standards are required for glycan arrays, characterizing substrate specificities of glycan-active enzymes, and to serve as retention-time or mobility standards for various separation techniques. This chapter describes a method for the rapid separation, and subsequent desalting, of glycans labeled with the highly fluorescent fluorophore 8-aminopyrene-1,3,6-trisulfonate (APTS). By using fluorophore-assisted carbohydrate electrophoresis (FACE) on polyacrylamide gels, a technique amenable to equipment readily available in most molecular biology laboratories, many APTS-labeled glycans can be simultaneously resolved. Excising specific gel bands containing the desired APTS-labeled glycans, followed by glycan elution from the gel by simple diffusion and subsequent solid-phase extraction (SPE)-based desalting, affords a single glycan species free of excess labeling reagents and buffer components. The described protocol also offers a simple, rapid method for the simultaneous removal of excess APTS and unlabeled glycan material from reaction mixtures. This chapter describes a FACE/SPE procedure ideal for preparing glycans for capillary electrophoresis (CE)-based enzyme assays, as well as for the purification of rare, commercially unavailable glycans from tissue culture samples.


EQ-5D-Y-3L and EQ-5D-Y-5L proxy report: psychometric performance and agreement with self-report.
Self-report is the standard for measuring people's health-related quality of life (HRQoL), including children. However, in certain circumstances children cannot report their own health. For this reason, children's HRQoL measures often provide both a self-report and a proxy-report form. It is not clear whether the measurement properties will be the same for these two forms. We investigated whether it would be beneficial to extend the classification system of the EQ-5D-Y proxy questionnaire from 3 to 5 response levels. The agreement between self-report and proxy-report was assessed for both EQ-5D-Y measures. The study included 286 pediatric patients and their caregivers as proxies. At three consecutive measurements-baseline, test-retest and follow-up-the proxies assessed the child's HRQoL using the EQ-5D-Y-3L, EQ-5D-Y-5L, the PedsQL Generic, and matched disease-specific instruments. The proxy versions of EQ-5D-Y-3L and EQ-5D-Y-5L were compared in terms of feasibility, distribution properties, convergent validity, test-retest and responsiveness. Agreement between both EQ-5D-Y proxy versions to their respective self-report versions was assessed at baseline and follow-up. The proportion of missing responses was 1% for the EQ-5D-Y-3L and 1.4% for the EQ-5D-Y-5L. The frequency of health state with no problems in all dimensions (11111) was slightly lower for the EQ-5D-Y-5L (21.3% vs 16.7%). Regarding the convergent validity with the PedsQL and disease-specific measures, the proxy versions of EQ-5D-Y-3L and EQ-5D-Y-5L had similar magnitudes of associations between similar dimensions. The means of test-retest coefficients between the two versions of the EQ-5D-Y proxy were comparable (0.83 vs. 0.84). Regarding reported improved conditions, responsiveness of the EQ-5D-Y-5L proxy (26.6-54.1%) was higher than that of the EQ-5D-Y-3L proxy (20.7-46.4%). Except for acutely ill patients, agreement between the EQ-5D-Y-5L proxy and self-reports was at least moderate. Extending the number of levels of the proxy version of EQ-5D-Y can improve the classification accuracy and the ability to detect health changes over time. The level structure of EQ-5D-Y-5L was associated with a closer agreement between proxy and self-report. The study findings support extending the EQ-5D-Y descriptive system from 3 to 5 levels when administered by a proxy, which is often the case in the pediatric population.


Demodectic infestation of the pilosebaceous follicle.
Scanning electron microscopy revealed Demodex folliculorum on the face surface of twenty healthy subjects. The ultrastructural morphology of Demodex and the follicle parasitization process are briefly illustrated.


Tracheopathia osteochondroplastica. A cause of unexpected difficulty in tracheal intubation.
A 60-year-old man presented for aortocoronary saphenous vein grafting; tracheal intubation was found to be difficult before surgery. Bronchoscopy at the time suggested tracheal carcinoma, but subsequent biopsy of the trachea demonstrated tracheopathia osteochondroplastica. The condition is described and its implications for anaesthetists are discussed.


Real-Time Communication: Creating a Path to COVID-19 Public Health Activism in Adolescents Using Social Media.
The COVID-19 pandemic and related public health efforts limiting in-person social interactions present unique challenges to adolescents. Social media, which is widely used by adolescents, presents an opportunity to counteract these challenges and promote adolescent health and public health activism. However, public health organizations and officials underuse social media to communicate with adolescents. Using well-established risk communication strategies and insights from adolescent development and human-computer interaction literature, we identify current efforts and gaps, and propose recommendations to advance the use of social media risk communication for adolescents during the COVID-19 pandemic and future disasters.


A potential probe set of fluorescence in situ hybridization for detection of lung cancer in bronchial brushing specimens.
The study aims to find candidate probes of fluorescence in situ hybridization (FISH) for detection of lung cancer with bronchial brushings and to evaluate whether the accuracy of diagnosing lung cancer by cytological deviant and genetic abnormalities is greater than that of cytology alone. Centromeric enumeration probes (CEPs) for chromosomes 2, 3, 6, 7, 8, 9, 11, 12, and 17 were analyzed using FISH in 74 surgical resection tissues, 32 operative margin tissues without tumor involvement of lung cancer, and 174 bronchial brushings. The aneuploidy rates of the tested probes were 61.7, 89.1, 80.0, 92.7, 65.0, 70.4, 66.7, 71.8, 68.9 % in tumor tissues, and 29.3, 58.9, 33.3, 69.6, 67.0, 40.3, 38.0, 49.3, 35.1 % in bronchial brushings. The combination of cytology and FISH using the three-probe set for chromosomes 3+7+8 significantly improved the sensitivity of bronchial brushing examination for lung cancer detection (P = 0.00003), especially squamous cell carcinoma (SCC), which increased from 78.0 to 98.2 %. The specificity of the 3+7+8 probe set was 94.6 %. Moreover, a high aneuploidy rate of the probe set in bronchial brushings was detected more often in SCCs (P = 0.029) and late-stage non-small-cell lung cancer (NSCLC) (P = 0.044). Kaplan-Meier curves indicated that adenocarcinoma (ADC) patients with high aneuploidy rate of CEP3 in tissue samples exhibited poorer overall survival (P = 0.016). FISH performed on cytology preparations is useful for confirmation of cancer diagnosis. The three-probe set, 3+7+8, has potential value for the detection of SCCs in bronchial brushings.


Effect of hyperthermia on the cytotoxicity of 2',2'-difluorodeoxycytidine (gemcitabine) in cultured SW1573 cells.
Difluorodeoxycytidine (dFdCyd, gemcitabine) was tested for cytotoxicity in cultured human lung-cancer cells SW1573 in combination with 1 hr hyperthermia at 43 degrees C. The results show that the timing is extremely important. Simultaneous application led to decreased cytotoxicity, whereas an interval of 20 or 24 hr between exposure to dFdCyd and hyperthermia led to enhanced cell killing. The decrease in cytotoxicity after simultaneous hyperthermia and dFdCyd probably results from inhibition of activation of dFdCyd to the triphosphate metabolite. The enhanced cytotoxicity in sequential application of dFdCyd and hyperthermia is not caused by accumulation of cells in a sensitive cell-cycle phase. Our results show that the G1 phase becomes relatively abundant 20 hr after exposure to 0.1 microM dFdCyd, approximately 48% versus 31% in control cultures. Presumably, inhibition by hyperthermia of repair of DNA damage plays a role. Our results confirm earlier data with regard to reutilization of activated dFdCyd at high cell density. dFdCyd was clearly more toxic to SW1573 cells at 4 x 10(5) cells per dish than at 400 cells per dish. This reutilization of activated drug is evidently not a restricted property of a particular cell line and may add to the value of the drug in cancer treatment.


Nasotracheal intubation awake in a patient with multiple fractures of the maxilla and cervical spine: A case report.
Nasotracheal intubation is an advanced airway modality used in specific contexts, such as limited mouth opening, macroglossia, cervical spine instability. In addition, it can be performed with the patient awake, especially when predictors a difficult airway are unknown. A 41-year-old male with a lesion in the C1 cervical vertebra, associated with a fracture of the right maxilla, was intubated through the nasopharyngeal route while awake. The forms of induction were discussed. Based on the mechanism of trauma and on the report of pain, associated with imaging examination, fracture of the body of the right maxilla and a complex fracture of the anterior arch of the C1 cervical vertebra were diagnosed. In this case, we present a patient with trauma to the face and spine who was intubated through the nasopharyngeal route while awake and guided by video laryngoscopy and using a rigid cervical collar. The patient was operated on under total general anesthesia (propofol and remifentanil) and plates and screws were placed for maxillary osteosynthesis. The pain was alleviated with a peripheral block of the trigeminal nerve of the maxillary branch with 0.5% levobupivacaine. The patient woke up from surgery, was extubated uneventfully and without pain. Cervical spine injuries were followed up by the neurosurgery team for conservative treatment. Patients with neck injury and facial trauma may need a definitive airway either for emergencies or for elective procedures. Intubating the awake patient may be an option when the anatomy of the cavity is unknown, and inducing the anesthetic act without this knowledge may be a inappropriate option, due to the risk of intubation/ventilation difficulties.


Origin of relationship between ferromagnetic response and damage in stretched systems.
This article presents a study whose purpose is to elucidate the damage effects in thin films on their magnetic response. Co40Fe40B20 and Ni80Fe20 films of different nanometric thicknesses were stretched by more than 10% and in situ probed by atomic force microscopy measurements to determine their irreversible mechanical behavior (multi-cracking, buckling). Once these phenomena have been well identified, magnetic behavior of these stretched systems has been studied by ferromagnetic resonance to measure resulting magnetic anisotropy and damping evolutions. All of these experimental studies show that the magnetic properties are mainly affected by the stresses generated during the damage but not by the local discontinuities induced by the numerous cracks and buckles. This is in particular confirmed by the almost zero sensitivity to the damage of the magnetic properties of Ni80Fe20 alloy which is known for its vanishing magnetostriction.


Binding and functional properties of concanavalin A and its derivatives. III. Interactions with indoleacetic acid and other hydrophobic ligands.
The binding of concanavalin A to various structures via hydrophobic interactions has been studied using a variety of physicochemical assays. It was found that concanavalin A binds to nonpolar compounds such as the plant auxin beta-indoleacetic acid and its structural analogue tryptophan and that this binding is independent of the saccharide-binding activity normally associated with the lectin. The results of equilibrium dialysis experiments on the binding of beta-indoleacetic acid were consistent with the presence of a single weak binding site per subunit of protein, having an association constant of about 7 X 10(2) M-1. Competition experiments using various nonpolar compounds such as o-iodobenzoic acid suggested that this hydrophobic binding site is located in the same cavity which binds the iodine-containing ligand as shown by x-ray crystallography. Concanavalin A also binds to lipid vesicles composed of dipalmitoylphosphatidylcholine or 12-O-tetradecanoyl phorbol-13-O-acetate. This binding to lipid membranes raises the possibility that the synergistic effects of concanavalin A and tetradecanoyl phorbol acetate on lymphocyte mitogenesis may be due in part to an interaction between lectin and the phorbol ester.


Die perioperative Gabe von Tranexamsäure.
The application of tranexamic acid (TXA) during endoprosthetic surgical procedures has significantly increased in recent years. Due its ability to reduce perioperative blood loss and avert the need for blood transfusions as well as wound drainage, TXA is becoming part of a 'standard practice'. However, TXA is currently not approved for the application during endoprosthetic procedures and therefore, a benefit-risk analysis should always be conducted. Prophylactic administration of TXA without prior patient consent is only justified if fibrinolytic bleeding is expected and there are no contraindications or relevant risk factors for thromboembolic complications. Respectively, no patient consent is required when a therapeutic dose of TXA is administered in the context of fibrinolytic bleeding. The following guidelines provide updated recommendations based on the current state of knowledge on TXA optimal timing, routes of administration and dosing regimen.


Effects of taurine deficiency and chronic methanol administration on rat retina, optic nerve and brain amino acids and monoamines.
A chronic methanol (MeOH) intoxication scheme (2 g/kg/day ip for 2 weeks) was carried out in Sprague-Dawley rats, previously depleted of folates with methotrexate (MTX). beta-Alanine (beta-Ala), 5%, was also administered to some animals in the drinking water. Amino acids were determined in plasma, retina, optic nerve, hippocampus and posterior cortex by HPLC with fluorescence detection and monoamines in retina, hippocampus and posterior cortex by electrochemical detection. Beta-Ala administration reduced taurine (Tau) levels in plasma, hippocampus and posterior cortex, but not in retina and optic nerve. Aspartate (Asp) concentration in the optic nerve was increased in MTX-MeOH treated animals, and the administration of beta-Ala did not modify this elevation. The association of beta-Ala with MTX-MeOH produced an increase of threonine, and a decrease of 5-hydroxytryptamine (5-HT) in the retina without modifying 5-hydroxyindoleacetic acid, whereas in the hippocampus an elevation of asparagine was observed. We conclude that, in the retina, beta-Ala in combination with MTX-MeOH increased serotonin and decreased dopamine (DA) turnover rate, and resulted in changes in the amino acid balance, that could affect glycinergic activity. On the other hand, in the hippocampus, Asp metabolism could be affected by Tau depletion with beta-Ala.


Canine babesiosis.
Canine babesiosis is a tickborne, protozoal, hemoparasitic disease that can cause varying degrees of hemolytic anemia, splenomegaly, thrombocytopenia, and fever. Babesia organisms frequently are classified as large or small. Large Babesia infections are attributed to one of three subspecies of Babesia canis. All small Babesia infections previously were attributed to B gibsoni, but molecular analysis and DNA sequencing have revealed that there are at least three small piroplasms infecting dogs. Correctly identifying the infectious agent is important for treatment planning and prognosis.


Posterior reversible encephalopathy syndrome in a survivor of valproate-induced acute liver failure: a case report.
Posterior reversible encephalopathy syndrome is an extremely rare radiological diagnosis that has not been reported previously in association with acute liver failure. A 6-year-old Sri Lankan girl developed acute liver failure with severe hepatic encephalopathy due to sodium valproate. She was successfully treated medically with N-acetylcysteine and L-carnitine. During recovery she again developed features of encephalopathy and had repeated convulsions associated with moderate hypertension. The diagnosis of posterior reversible encephalopathy syndrome was made on clinical and radiological grounds and she showed a gradual improvement with control of blood pressure. This report adds to the evidence behind treatment of valproate-induced acute liver failure with N-acetylcysteine and L-carnitine and illustrates a rare but interesting association between acute liver failure and posterior reversible encephalopathy syndrome.


Aprepitant, granisetron, and dexamethasone versus palonosetron and dexamethasone for prophylaxis of cisplatin-induced nausea and vomiting in patients with upper gastrointestinal cancer: a randomized crossover phase II trial (KDOG 1002).
We conducted a randomized trial to compare the safety and effectiveness of aprepitant, granisetron, and dexamethasone (AGD) with those of palonosetron and dexamethasone (PD) in patients who received highly emetogenic chemotherapy (HEC). Patients with esophageal or gastric cancer who were scheduled to receive HEC including at least 60 mg/m of cisplatin as the first-line treatment were randomly assigned to receive AGD (oral aprepitant 125 mg on day 1 and 80 mg on days 2-3; intravenous granisetron 3 mg on day 1; intravenous dexamethasone 6.6 mg on day 1 and oral dexamethasone 4 mg on days 2-3) or PD (intravenous palonosetron 0.75 mg on day 1; intravenous dexamethasone 13.2 mg on day 1 and oral dexamethasone 8 mg on days 2-3). The primary endpoint was a complete response during the overall study period (0-120 h after the start of chemotherapy) in the first cycle. Eighty-five patients were enrolled, and 84 were eligible. The complete response rate did not differ between the treatment groups, but the proportion of patients with no vomiting was significantly higher in the AGD group than in the PD group (81.4 vs. 58.5%; P=0.031). The results of a quality-of-life survey indicated that the proportion of patients with no or minimal impact on daily life in the vomiting domain was significantly higher in the AGD group (79.1 vs. 53.7%; P=0.020). The primary endpoint of complete response was not achieved, but AGD seems to be more effective than PD for the prevention of HEC-induced vomiting.


A genomic enhancer signature associates with hepatocellular carcinoma prognosis.
Lifestyle and environmental-related exposures are important risk factors for hepatocellular carcinoma (HCC), suggesting that epigenetic dysregulation significantly underpins HCC. We profiled 30 surgically resected tumours and the matched adjacent normal tissues to understand the aberrant epigenetic events associated with HCC. We identified tumour differential enhancers and the associated genes by analysing H3K27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) and Hi-C/HiChIP data from the resected tumour samples of 30 patients with early-stage HCC. This epigenome dataset was analysed with previously reported genome and transcriptome data of the overlapping group of patients from the same cohort. We performed patient-specific differential expression testing using multiregion sequencing data to identify genes that undergo both enhancer and gene expression changes. Based on the genes selected, we identified two patient groups and performed a recurrence-free survival analysis. We observed large-scale changes in the enhancer distribution between HCC tumours and the adjacent normal samples. Many of the gain-in-tumour enhancers showed corresponding upregulation of the associated genes and vice versa, but much of the enhancer and gene expression changes were patient-specific. A subset of the upregulated genes was activated in a subgroup of patients' tumours. Recurrence-free survival analysis revealed that the patients with a more robust upregulation of those genes showed a worse prognosis. We report the genomic enhancer signature associated with differential prognosis in HCC. Findings that cohere with oncofoetal reprogramming in HCC were underpinned by genome-wide enhancer rewiring. Our results present the epigenetic changes in HCC that offer the rational selection of epigenetic-driven gene targets for therapeutic intervention or disease prognostication in HCC. Lifestyle and environmental-related exposures are the important risk factors of hepatocellular carcinoma (HCC), suggesting that tumour-associated epigenetic dysregulations may significantly underpin HCC. We profiled tumour tissues and their matched normal from 30 patients with early-stage HCC to study the dysregulated epigenetic changes associated with HCC. By also analysing the patients' RNA-seq and clinical data, we found the signature genes - with epigenetic and transcriptomic dysregulation - associated with worse prognosis. Our findings suggest that systemic approaches are needed to consider the surrounding cellular environmental and epigenetic changes in HCC tumours.


Bran data of total flavonoid and total phenolic contents, oxygen radical absorbance capacity, and profiles of proanthocyanidins and whole grain physical traits of 32 red and purple rice varieties.
Phytochemicals in red and purple bran rice have potential health benefit to humans. We determined the phytochemicals in brans of 32 red and purple global rice varieties. The description of the origin and physical traits of the whole grain (color, length, width, thickness and 100-kernel weight) of this germplasm collection are provided along with data of total flavonoid and total phenolic contents, oxygen radical absorbance capacity and total proanthocyanidin contents. The contents and proportions of individual oligomers, from degree of polymerization of monomers to 14-mers, and polymers in bran of these 32 rice varieties are presented (DOI: http://dx.doi.org/10.1016/j.foodchem.2016.04.004) [1].


Magnetic resonance imaging in cervical cancer: a basis for objective classification.
Conventional clinical staging of cervical cancer is subjective because it is based on palpatory findings and inadequate because it cannot assess the single most important prognostic factor--tumor size. To determine the exactitude of in vivo MRI measurements of tumor volume, 22 patients with invasive cervical cancer were studied before surgery. The volumes obtained by MRI correlated well (r = 0.983) with those obtained by histomorphometric analysis of the surgical specimens, but only weakly with clinical stage. MRI may provide a basis for precise classification of cervical cancer and for objective comparison of surgery and radiotherapy.


Vulnerable Dark Triad Personality Facets Are Associated with Religious Fundamentalist Tendencies.
This study explores the possibility that religious fundamentalism (RF) may be linked to deficits in personality structure, which is in contrast to the general assumption that religiosity and spirituality are positively related to mature personality development. To test this hypothesis, 327 (232 female) college students completed the Multidimensional Inventory for Religious/Spiritual Well-Being together with the Innsbrucker Religious Fundamentalism Scale. In addition, the 'vulnerable dark triad' of personality ('vulnerable narcissism', subscale of the Pathological Narcissism Inventory; 'secondary psychopathy', subscale of Levenson's Self-Report Psychopathy Scale; 'borderline personality', of the Borderline Personality Inventory) was assessed. In general, the relation between spirituality and healthy personality functioning was confirmed. In addition to greatly overlapping with 'general religiosity' (p < 0.001), RF was also relevantly predicted by narcissistic ('hiding the self') and borderline ('primitive defenses') personality facets (p < 0.05 for both). Based on these preliminary data, we conclude that specific structural deficits in personality might lead to more rigorous variants of religious/spiritual beliefs such as RF. Further research in clinical surroundings as well as in religious extremist groups is recommended.


Minimally Invasive Ways to Monitor Changes in Cardiocirculatory Fitness in Running-based Sports: A Systematic Review.
This systematic review provides a synthesis of research investigating submaximal protocols to monitor changes in cardiocirculatory fitness in running-based sports. Following PRISMA guidelines, 2,452 records were identified and 14 studies, representing 515 athletes, satisfied the eligibility criteria. While most studies found large associations between changes in heart rate at standardized, submaximal running speeds and changes in aerobic fitness (r=0.51-0.88), three studies failed to establish a relationship (r=0.19-0.35). The intensity of the submaximal protocols seems to be relevant, with changes in running speeds at 90% of maximal heart rate showing larger relationships with changes in aerobic fitness (r=0.52-0.79) compared to 70% of maximal heart rate (r=0.24-0.52). Conversely, changes in post-exercise heart rate variability were very largely associated with changes in aerobic fitness when the testing protocols were less intense (70% of maximal heart rate) (r=0.76-0.88), but not when the test required participants to achieve 90% of their maximal heart rate (r=-0.02-0.06). Studies on post-exercise heart rate recovery revealed inconclusive results (r=-0.01- -0.55), while rate of heart rate increase may be a promising athlete monitoring metric (r=0.08- -0.84) but requires further research. In summary, when executed, analyzed, and interpreted appropriately, submaximal protocols can provide valuable information regarding changes in athlete cardiocirculatory fitness.


Specialty Showcase Days: Can Specialist Careers Workshops Improve The Consideration Of ENT For Medical Students?
We hypothesize that poor consideration of specialist surgery is due to a lack of exposure to information about careers and practice itself. Ear, Nose, and Throat (ENT) surgery is given little weight in medical school curricula, despite ENT problems being extremely common. Our objective is to assess whether a specialty showcase day was sufficient to boost informed consideration of this career. We designed a half-day course involving an interactive careers workshop exploring ENT as a specialty choice, alongside simulation stations of commonly presenting ENT problems led by ENT doctors. We used pre- and post-course evaluation sheets to explore factors that encourage and discourage students from surgical careers and perceptions of ENT. A large proportion of UK medical schools do not offer ENT placements, and of those that do, nearly half are not compulsory. This leaves students unaware of ENT as a career option and unclear about what an ENT career comprises. Our half-day course took place in the simulation suite at St Mary's Hospital, London. Medical students were mainly in their third year of study and had aspirations towards a variety of surgical and non-surgical careers, with a minority aspiring towards ENT before the course. Our results demonstrate that all students found the session useful and had a much better understanding of ENT practice, with almost all students leaving more likely to consider a career in ENT. We would like to repeat this session in different student year groups and compare their perceptions with our results. We find our results a good case for including informative careers workshops as part of medical school teaching. We pose that interactive workshops exploring specialist surgical careers are a valid way to enable students in making informed career decisions - particularly in specialties that are under-represented at medical school.


Wnt signaling: relevance to beta-cell biology and diabetes.
Interest in the importance of Wnt signaling in diabetes has risen after identification of the transcription factor TCF7L2, a component of this pathway, as a strong risk factor for type 2 diabetes. Here, we review emerging new evidence that Wnt signaling influences endocrine pancreas development and modulates mature beta-cell functions including insulin secretion, survival and proliferation. Alterations in Wnt signaling might also impact other metabolic tissues involved in the pathogenesis of diabetes, with TCF7L2 proposed to modulate adipogenesis and regulate GLP-1 production. Together, these studies point towards a role for Wnt signaling in the pathogenesis of type 2 diabetes, highlighting the importance of further investigation of this pathway to develop new therapies for this disease.


Mutagenesis of Propionibacterium acnes and analysis of two CAMP factor knock-out mutants.
P. acnes is a skin commensal that is frequently associated with inflammatory diseases such as acne vulgaris. Despite the availability of the genome sequence functional studies on P. acnes are scarce due to a lack of methods for genetic manipulation of this bacterium. Here we present an insertional mutagenesis approach for the inactivation of specific P. acnes genes. The gene of interest can be disrupted and replaced with an erythromycin-resistance cassette by employing homologous recombination. We used this method to generate knock-out mutants of camp2 (PPA0687) and camp4 (PPA1231), encoding CAMP factor homologs with predicted co-hemolytic activities. The successful inactivation of the two genes was confirmed by PCR and Western blotting experiments using specific anti-CAMP2/CAMP4 sera. The Δcamp2 but not the Δcamp4 mutant exhibited reduced hemolytic activity in the CAMP reaction with sheep erythrocytes, indicating that CAMP2 is the major active co-hemolytic factor of P. acnes. The biological relevance of the CAMP factors remains unclear as disruption of camp2 or camp4 did not significantly alter the transcriptome response of HaCaT cells to P. acnes. The here presented insertional mutagenesis approach will facilitate future studies on P. acnes.