Proliferation and differentiation study of melatonin functionalized polycaprolactone/gelatin electrospun fibrous scaffolds for nerve tissue engineering.
Melatonin (MLT), a pineal neurohormone with multiple neuroprotective, is often used for peripheral nerve recovery and regenerated nerve proliferation. In this study, Polycaprolactone/Gelatin (PG) fibrous electrospun scaffolds with various percentages of MLT (0, 1, 2, and 4%wt) were fabricated for nerve cell growth, the effects of different concentrations of MLT within PG fibers (PG, PGMLT1, PGMLT2, and PGMLT4) on the proliferation and differentiation for PC12 cells were quantitatively evaluated. The microstructures and morphologies of these scaffolds were analyzed by FE-SEM and digital camera. Fourier transform infrared spectrometer (FTIR), X-ray photoelectron spectroscopy (XPS), and Water Contact Angle (WCA) were used to study the composition, ratio and properties of MLT functionalized PG scaffolds. MTT and CLSM analysis showed that appropriate amount of MLT was beneficial to the proliferation of PC12 cell. MLT can also promote cell differentiation, neurite germination, the expression levels of MAP2 mRNA and protein were dramatically increased on the composite scaffolds with the increase of MLT content, moderate addition of MLT (PGMLT2, 2%) had a prominent enhancement for neurite length. This work would provide a more comprehensive reference for further researches on MLT functionalized composite scaffolds and suggest that high-performance PGMLT fibrous scaffolds could be a promising alternative for nerve repair.


Numerical study and theoretical performance limit of interconnected multi-capillary gas chromatography columns with perfectly ordered pillar patterns.
We present the results of a theoretical and numerical study of the chromatographic performance of a novel type of microfabricated GC column. The column consists of an array of rectangular flow diverters (pillars), creating a network of perfectly ordered, interconnected and tortuous flow-through paths. Using van Deemter and kinetic plots of simulated band broadening data, we could demonstrate that the proposed column structure performs as a bundle of parallel open-tubular capillaries with rectangular cross-section, connected by a regular pattern of channel-intermixing points that allow compensating for inevitable channel-to-channel differences in migration velocity without adding any significant dispersion themselves. The established kinetic plots also allowed to propose design rules for the optimal distance between the pillars as a function of the desired separation efficiency and the available column pressure. The simulations also allowed establishing an expression for the plate height as a function of the velocity of the carrier gas. Results are also compared to the results of a recent experimental study.


High yields of specific hybridomas obtained by electrofusion of murine lymphocytes immunized in vivo or in vitro.
We have studied the use of electrofusion to obtain hybridomas producing antigen-specific antibodies after immunization of murine lymphocytes in vitro. Under optimal conditions fusion frequencies of the order of magnitude of 10(-3) were obtained, which is approximately 80-fold higher than the mean value obtained with fusion induced by polyethylene glycol. The number of antigen-specific hybridomas was also increased in a comparable way. The high yields of specific hybridomas observed with electrofusion were independent of the immunization procedure, the antigen or the hapten of interest, or the sources of the lymphocytes. The data presented in this paper indicate that electrofusion may be an extremely attractive alternative method for immortalization of human lymphocytes following immunization in vitro.


Treatment of bacterial vaginosis in pregnancy in order to reduce the risk of spontaneous preterm delivery - a clinical recommendation.
Bacterial vaginosis (BV) is characterized by a dysbiosis of the vaginal microbiota with a depletion of Lactobacillus spp. In pregnancy, prevalence's between 7 and 30% have been reported depending on the study population and the definition. BV may be associated with an increased risk of spontaneous preterm delivery (sPTD). However, it is controversial whether or not BV-positive pregnant women will benefit from treatment to reduce the risk of sPTD. We could not identify any good-quality guideline addressing this issue. Consequently we aimed to produce this clinical recommendation based on GRADE. Systematic literature searches were conducted in the following databases: Guidelines International Network: G-I-N, Medline, Embase, The Cochrane Database of Systematic Reviews, Web of Science and http://www.clinicaltrials.gov from 1999 to 3 October 2014. Hence, nine guidelines, 34 reviews, 18 randomized controlled trials and 12 observational studies were included. The GRADE quality of evidence was consistently low or very low, primarily because none of the risk ratios (RR) for the risk of sPTD at <37 weeks were statistically significant. Concerning treatment with metronidazole, RR was 1.11 (95% CI 0.93-1.34) in low-risk pregnancies and 0.96 (95% CI 0.78-1.18) in high risk pregnancies. Concerning treatment with clindamycin at any gestational age, the RR was 0.87 (95% CI 0.73-1.05). This systematic review gives a strong recommendation against treatment with metronidazole and a weak recommendation against treatment with clindamycin to reduce the sPTD rate in both high-risk and low-risk pregnancies with BV.


A Real-World, Population-Based Study for the Incidence and Outcomes of Neuroendocrine Neoplasms of Nondigestive, Nonpulmonary Primary.
The aim of this study was to assess incidence and outcomes of neuroendocrine neoplasms (NENs) arising from primary sites other than digestive organs, lung, or thymic gland. Surveillance, Epidemiology, and End Results database (1975-2016) was accessed, and cases of NENs arising from primary sites other than digestive organs, lung, or thymic gland were reviewed. Overall and cancer-specific survival outcomes for NENs arising from different organs compared with small intestinal NENs were evaluated. A total of 4405 patients were included in the study. Compared with small intestinal NENs, some NENs arising from uncommon sites in the current study have worse cancer-specific survival (hazard ratio [HR] for genitourinary vs small intestinal NENs, 1.80; 95% confidence interval [CI], 1.44-2.25; HR for gynecological vs small intestinal NENs, 1.88; 95% CI, 1.52-2.33). When the analysis was limited for patients with distant stage only, small intestinal NENs have better outcomes compared with genitourinary and gynecological NENs (HR for genitourinary NENs with distant stage vs small intestinal NENs with distant stage, 1.38; 95% CI, 1.01-1.88; HR for gynecological NENs with distant stage vs small intestinal NENs with distant stage, 2.02; 95% CI, 1.54-2.66). Compared with small intestinal NENs, NENs arising from uncommon sites (such as genitourinary, gynecological) have worse survival outcomes.


The effect of Baduanjin on the balancing ability of older adults: A systematic review and meta-analysis.
To systematically evaluate the effect of Baduanjin on the balancing ability of older adults. The systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Six electronic databases were searched for eligible studies. Data synthesis and statistical analysis using a random effects model were performed with Review Manager 5.4. Random-effects weights were used to pool the effect sizes. Publication bias was assessed by funnel plot. A total of 17 RCTs involving 1,267 patients were identified. The meta-analysis showed that the Baduanjin group was significantly superior to the control group in balancing performance measured by Berg balance scale [mean difference (MD) 4.82; 95% confidence interval (CI) 3.40 to 6.24, P < 0.00001], Timed Up and Go (MD -2.21, 95% CI -2.69 to -1.74, P < 0.00001) and Eye Closed One Leg Standing Balance (MD 2.01, 95% CI 0.79 to 3.23, P < 0.00001) tests. Baduanjin can effectively affect the balancing ability of older adults. More high-quality evidence-based studies are required to confirm these findings. [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=293183], identifier [CRD42021293183].


Larch Forests of Middle Siberia: Long-Term Trends in Fire Return Intervals.
Fire history within the northern larch forests of Central Siberia was studied (65+°N). Fires within this area are predominantly caused by lightning strikes rather than human activity. Mean fire return intervals (FRI) were found to be 112 ± 49 years (based on fire scars) and 106 ± 36 years (based on fire scars and tree natality dates). FRI were increased with latitude increase, and observed to be about 80 years at 64°N, about 200 years near the Arctic Circle, and about 300 years nearby the northern range limit of larch stands (~71°+N). Northward FRI increase correlated with incoming solar radiation (r = - 0.95). Post Little Ice Age (LIA) warming (after 1850) caused approximately a doubling of fire events (in comparison with a similar period during LIA). The data obtained support a hypothesis of climate-induced fire frequency increase.


Surfomics: shaving live organisms for a fast proteomic identification of surface proteins.
Surface proteins play a critical role in the interaction between cells and their environment, as they take part in processes like signaling, adhesion, transport, etc. In pathogenic microorganisms, they can also participate in virulence or cytotoxicity. As these proteins have the highest chances to be recognized by the immune system, they are often the targets for the discovery of new vaccines. In addition, they can serve for the development of serological-based tools to diagnose infectious diseases. First-generation proteomic strategies for the identification of surface proteins rely on the biochemical fractionation and/or enrichment of this group of molecules or organelles containing them. However, in the last years, a novel second-generation approach has been developed, consisting of the digestion of live, intact cells with proteases, so that surface-exposed moieties (i.e. the "surfome" of a cell) are "shaved" and analyzed by LC/MS/MS. Here we review such a strategy, firstly set up and developed in Gram-positive bacteria, and further applied to Gram-negative bacteria, unicellular fungi, and also pluricellular organisms. We also discuss the advantages and inconvenients of the approach, and the still unresolved question about the intriguing presence of proteins predicted as cytoplasmic in the surfomes. This article is part of a Special Issue entitled: Trends in Microbial Proteomics.


Experimental irradiation of the rat ureter: the effects of field size and the presence of contrast medium on incidence and latency of hydronephrosis.
Following X-irradiation of a 1.5 cm length of rat ureter, hydronephrosis developed after doses down to 10 Gy. The estimated ED50 was 11.8 Gy. In the dose range 37.4 Gy to 17.5 Gy there was a significant increase in latency with decreasing dose, but at lower doses the latency did not increase further. Reducing the length of ureter irradiated to 0.5 cm or 0.8 cm caused a decrease in incidence of hydronephrosis and longer latency periods. The ED50 for rats irradiated to 0.5 cm of ureter was 29.6 Gy. The possibility that secondary radiation produced as a result of interaction between X-radiation and iodinated contrast medium might affect the radiation induction of hydronephrosis was investigated. No difference was found between groups of rats irradiated with or without injection of contrast media.


Cell biology of the chloroplast symbiosis in sacoglossan sea slugs.
Chloroplasts removed from their species of origin may survive for various periods and even photosynthesize in foreign cells. One of the best studied and impressively long, naturally occurring examples of chloroplast persistence, and function inside foreign cells are the algal chloroplasts taken up by specialized cells of certain sacoglossan sea slugs, a phenomenon called chloroplast symbiosis or kleptoplasty. Among sacoglossan species, kleptoplastic associations vary widely in length and function, with some animals immediately digesting chloroplasts, while others maintain functional plastids for over 10 months. Kleptoplasty is a complex process in long-term associations, and research on this topic has focused on a variety of aspects including plastid uptake and digestive physiology of the sea slugs, the longevity and maintenance of symbiotic associations, biochemical interactions between captured algal plastids and slug cells, and the role of horizontal gene transfers between the sea slug and algal food sources. Although the biochemistry underlying chloroplast symbiosis has been extensively examined in only a few slug species, it is obvious that the mechanisms vary from species to species. In this chapter, we examine those mechanisms from early discoveries to the most current research.


Hospital admission and community treatment of mental disorders in England from 1998 to 2012.
The number of psychiatric hospital beds in England has declined since the 1950s. Since the early 2000s, mental health staff increasingly work in community treatment teams. We analysed recent trends in hospital and community treatment in England for eight mental health diagnoses. We obtained data from the UK Government Health and Social Care Information Centre covering the period 1998 to 2012. We analysed hospital admissions and length of stay for each diagnosis each year using linear regression. We studied associations among admissions, community treatment and hospital bed availability each year using structural equation modeling. The number of mental health beds fell 39%, from 37,000 in 1998 to 22,300 in 2012. Hospital admissions for five diagnoses declined significantly (depression, bipolar disorder, schizophrenia, dementia and obsessive compulsive disorder, P<.01 or P<.001). The strongest decline for depression involved 1000 fewer admissions each year. Admissions for three disorders increased significantly (posttraumatic stress disorder, eating disorders and alcohol-related disorders, P<.01 or P<.001). Alcohol-related admissions increased most strongly, by more than 1700 a year, and were significantly associated with increasing liver fibrosis and cirrhosis admissions (Pearson's r=0.89, P<.001) across the National Health Service (NHS) and the affordability of alcohol (Pearson's r=0.76, P<.01). The median length of stay declined significantly for four diagnoses (P<.001); the other four diagnoses did not change significantly. Depression had the steepest decline of almost 1 less day in hospital per admission per year. Almost 300 more patients were sectioned under the Mental Health Act each year. Community activity had relatively little effect on admissions, and its direct effect was not significantly different from zero. Years with more psychiatric beds had more admissions. Mental health bed numbers have declined significantly in England. Annual admissions and lengths of stay declined for a range of severe mental disorders including schizophrenia, bipolar disorder and depression. The fall in available beds can account for much of the decline in admissions. National reports of crisis team activity are not associated with declines in hospital admissions. There may be significant needs, especially of depressive patients, not being met by secondary community services, such as 24-hour observation and care. This calls for policy review and further epidemiological study of morbidity, mortality and health needs associated with mental disorder in the community.


Erectile dysfunction (ED) after ischemic stroke: association between prevalence and site of lesion.
Stroke may cause or worsen erectile dysfunction (ED). Post-stroke ED prevalence and association with stroke location are not well established. Therefore, we assessed post-stroke ED prevalence in relation to ischemic lesion locations and stroke severity. In 57 men (62.6 ± 10.5 years) who had ischemic stroke within 24 months prior to evaluation, we used the five-item International Index of Erectile Function questionnaire (IIEF5) to evaluate ED prevalence after stroke and retrospectively 3 months prior to stroke. IIEF5 scores range from 5 to 25; scores below 22 indicate ED. We estimated stroke severity upon hospital admission, using the National Institute of Health Stroke Scale (NIHSS), and determined stroke location from cranial computed tomography or magnetic resonance imaging. We compared pre- and post-stroke results with those of 22 control persons (61.7 ± 11.2 years), calculated correlations between IIEF5 scores and NIHSS scores, and compared ED prevalence with stroke locations (significance: p < 0.05). ED was reported by 45/57 patients after stroke, 26/57 patients before stroke, and 6/22 control persons. Patients' IIEF5 values were significantly lower [median 16 interquartile range (IQR) 3.5-20.5] after than before stroke (median 23, IQR 19.0-24.0) and lower than in controls (median 24, IQR 19.8-25.0). Pre- and post-stroke IIEF5 scores did not correlate with the patients' NIHSS scores at stroke onset (p > 0.05). ED was associated with middle cerebral artery infarction in 27/34, posterior cerebral artery infarction in 4/5, anterior cerebral artery infarction in 1/1, basal ganglia infarction in 3/3, brain stem infarction in 8/10, cerebellar infarction in 2/5, and lesions in more than one region in 1/1 patients. Disruption of the central network assuring erection might contribute to increased ED severity and prevalence after stroke. Anti-erectile effects of functional and psychological impairment or medication added after stroke may also contribute to ED but must be evaluated in larger patients groups.


Nubp2 is required for cranial neural crest survival in the mouse.
The N-ethyl-N-nitrosourea (ENU) ←forward genetic screen is a useful tool for the unbiased discovery of novel mechanisms regulating developmental processes. We recovered the dorothy mutation in such a screen designed to recover recessive mutations affecting craniofacial development in the mouse. Dorothy embryos die prenatally and exhibit many striking phenotypes commonly associated with ciliopathies, including a severe midfacial clefting phenotype. We used exome sequencing to discover a missense mutation in nucleotide binding protein 2 (Nubp2) to be causative. This finding was confirmed by a complementation assay with the dorothy allele and an independent Nubp2 null allele (Nubp2null). We demonstrated that Nubp2 is indispensable for embryogenesis. NUBP2 is implicated in both the cytosolic iron/sulfur cluster assembly pathway and negative regulation of ciliogenesis. Conditional ablation of Nubp2 in the neural crest lineage with Wnt1-cre recapitulates the dorothy craniofacial phenotype. Using this model, we found that the proportion of ciliated cells in the craniofacial mesenchyme was unchanged, and that markers of the SHH, FGF, and BMP signaling pathways are unaltered. Finally, we show evidence that the phenotype results from a marked increase in apoptosis within the craniofacial mesenchyme.


Temporal Dynamics of Corticocortical Inhibition in Human Visual Cortex: A TMS Study.
Paired-pulse transcranial magnetic stimulation (ppTMS) has been used extensively to probe local facilitatory and inhibitory function in motor cortex. We previously developed a reliable ppTMS method to investigate these functions in visual cortex and found reduced thresholds for net intracortical inhibition compared to motor cortex. The current study used this method to investigate the temporal dynamics of local facilitatory and inhibitory networks in visual cortex in 28 healthy subjects. We measured the size of the visual disturbance (phosphene) evoked by stimulating visual cortex with a fixed intensity, supra-threshold test stimulus (TS) when that TS was preceded by a sub-threshold conditioning stimulus (CS). We manipulated the inter-stimulus interval (ISI) and assessed how the size of the phosphene elicited by the fixed-intensity TS changed as a function of interval for two different CS intensities (45% and 75% of phosphene threshold). At 45% of threshold, the CS produced uniform suppression of the phosphene elicited by the TS across ISIs ranging from 2 to 200 ms. At 75% of threshold, the CS did not have a significant effect on phosphene size across the 2-15 ms intervals. Intervals of 50-200 ms exhibited statistically significant suppression of phosphenes, however, suppression was not uniform with some subjects demonstrating no change or facilitation. This study demonstrates that the temporal dynamics of local inhibitory and facilitatory networks are different across motor and visual cortex and that optimal parameters to index local inhibitory and facilitatory influences in motor cortex are not necessarily optimal for visual cortex. We refer to the observed inhibition as visual cortex inhibition (VCI) to distinguish it from the phenomenon reported in motor cortex.


MULCOX2: a general computer program for the Cox regression analysis of multivariate failure time data.
Multivariate failure time data is commonly encountered in biomedicine, because each study subject may experience multiple events or because there exists clustering of subjects such that failure times within the same cluster are correlated. MULCOX2 implements a general statistical methodology for analyzing such data. This approach formulates the marginal distributions of multivariate failure times by Cox proportional hazards models without specifying the nature of dependence among related failure times. The baseline hazard functions for the marginal models may be identical or different. A variety of statistical inference can be made regarding the effects of (possibly time-dependent) covariates on the failure rates. Although designed primarily for the marginal approach, MULCOX2 is general enough to implement several alternative methods. The program runs on any computer with a FORTRAN compiler. The running time is minimal. Two illustrative examples are provided.


Radiologic Characteristics of Surgically Resected Non-Small Cell Lung Cancer With ALK Rearrangement or EGFR Mutations.
Radiogenomic features are predictive of anaplastic lymphoma kinase (ALK) rearrangement in surgically resected non-small cell lung cancer (NSCLC). ALK rearrangement was screened by fluorescent in situ hybridization in 497 patients with resected NSCLC. Of these, 198 patients screened for both ALK and epidermal growth factor receptor (EGFR) mutation were enrolled. Clinicopathologic findings, survival after surgical procedure, computed tomographic (CT) features, and maximum standardized uptake value according to different genotypes were investigated with univariate and multivariate analyses. A receiver operating characteristic (ROC) curve analysis was performed to quantify the predictive value of these factors. The prevalence of ALK positivity in resected NSCLC was 5.0% (25 of 497). Patients with ALK rearrangement showed significant differences in terms of patient's age (p = 0.006 for ALK versus EGFR, and 0.04 for ALK versus wild type [WT]/WT, respectively), solid lesion (p = 0.0074 for ALK versus EGFR), degree of contrast enhancement (p = 0.0006 for ALK versus EGFR), and lesion margin (p = 0.0011 for ALK versus EGFR, and 0.0314 for ALK versus WT/WT, respectively) compared with EGFR mutant and WT/WT cohorts. Multivariate analysis revealed that young age, solid lesion, lobulated margin, and hypoattenuation at contrast-enhanced CT scan were independent predictors of ALK positivity (p = 0.027, 0.046, 0.001, 0.021, respectively). The area under the ROC curve of the predictive model was 0.832, which suggests good discrimination. ALK-rearranged lung cancer has characteristic clinical and imaging features compared with EGFR mutant or WT/WT cohorts. Our findings suggest that young age, lobulated margin, solid lesion, and hypoattenuation at contrast-enhanced CT scan are important predictors of ALK-rearranged lung cancer.


Minocycline does not affect long-term potentiation in the anterior cingulate cortex of normal adult mice.
It has been reported that activated microglia plays important roles in chronic pain-related sensory signaling at the spinal cord dorsal horn. Less is known about the possible contribution of microglia to cortical plasticity that has been found to be important for chronic pain. In the present study, we used a 64-channel multi-electrode array recording system to investigate the role of microglia in cortical plasticity of the anterior cingulate cortex (ACC) in normal adult mice. We found that bath application of minocycline, an inhibitor of microglial activation, had no effect on postsynaptic LTP (post-LTP) induced by theta burst stimulation in the ACC. Furthermore, presynaptic LTP (pre-LTP) induced by the combination of low-frequency stimulation with a GluK1-containing kainate receptor agonist was also not affected. The spatial distribution of post-LTP or pre-LTP among the cingulate network is also unaltered by minocycline. Our results suggest that minocycline does not affect cingulate plasticity and neurons are the major player in pain-related cortical plasticity.


Segmental aponeurectomy with Z-Plasty as a treatment option in Dupuytren's disease: A retrospective cohort study.
Aponeurectomy remains the reference standard treatment for digit tethering by palmar fascial cords in Dupuytren's disease but is associated with a substantial complication rate. An alternative technique decreases metacarpophalangeal joint (MCPJ) flexion contracture by combining palmar segmental aponeurectomy with Z-plasty skin closure. The primary objective of this study was to assess range of motion of the operated ray after the procedure. The secondary objectives were to assess the complication rate and to determine the recurrence rate after at least 1 year. Palmar segmental aponeurectomy with Z-plasty closure may provide the advantages of aponeurectomy while decreasing the surgical risk and recurrence rate. A retrospective study was conducted in 16 patients with predominant MCPJ flexion contracture due to a well-defined palmar fascial cord. Anaesthesia was loco-regional. The Z-plasty design involved a longitudinal incision along the palmar cord with an oblique incision at each end at a 60° angle to the longitudinal incision. The length of the aponeurectomy was about 1.5cm, to allow full MCPJ extension. In all, the 16 patients-13 males and 3 females-had 17 segmental palmar aponeurectomy procedures with Z-plasty closure. Mean operative time was 18minutes. Before surgery, mean loss of extension was 47° at the MCP joint and 15° at the corresponding proximal interphalangeal joint (PIPJ). Immediately after surgery, a 97% improvement in MCPJ extension was noted, leaving a mean extension deficit of 1.25°. Mean follow-up was 18.9 months. No complications occurred. Two patients experienced a recurrence. Segmental palmar aponeurectomy as described by Moermans in 1991 improves extension similarly to extensive aponeurectomy but has a lower complication rate. Z-plasty provides good exposure of the pedicles and takes advantage of the greater pliability of the skin on either side of the cord to lengthen the skin by 75%, thereby limiting the risk of the complications seen with needle aponeurotomy. Segmental palmar aponeurectomy with Z-plasty has a role in the management of Dupuytren's disease with flexion contracture predominantly involving the MCPJ.


Variable NK cell receptors and their MHC class I ligands in immunity, reproduction and human evolution.
Natural killer (NK) cells have roles in immunity and reproduction that are controlled by variable receptors that recognize MHC class I molecules. The variable NK cell receptors found in humans are specific to simian primates, in which they have progressively co-evolved with MHC class I molecules. The emergence of the MHC-C gene in hominids drove the evolution of a system of NK cell receptors for MHC-C molecules that is most elaborate in chimpanzees. By contrast, the human system of MHC-C receptors seems to have been subject to different selection pressures that have acted in competition on the immunological and reproductive functions of MHC class I molecules. We suggest that this compromise facilitated the development of the bigger brains that enabled archaic and modern humans to migrate out of Africa and populate other continents.


The components of executive functioning in a cohort of patients with chronic schizophrenia: a multiple single-case study design.
We examined the fractionation of executive functioning performance in ninety patients with schizophrenia, who were tested for initiation, sustained attention, switching/flexibility, attention allocation and impulsivity/disinhibition. The participants were also given tests of general intelligence and memory. We analysed the executive functioning performance of individual patients against normative data from our laboratory, and summary scores for all of the executive functioning components were computed. For each component, participants were classified as having impairment with a test performance of 1.5 standard deviations or more from the norm of the corresponding test. Of all of the participants, 27.8% (n=25) demonstrated poor performance in all of the components, and 5.6 % (n=5) exhibited intact or fair performance in all of the components. Furthermore, 18.9% (n=17) showed intact or fair performance in one component, 16.7% (n=15) in two components, 21.1% (n=19) in three components and 10% (n=9) in four components. The groups did not differ in education, gender or duration of illness, but the group that showed impaired performance in all of the components demonstrated the most severe psychotic symptoms after controlling for background intelligence, age and medication. The differential breakdown for the executive functioning performance across the participants suggests that the fractionation of central executive functioning occurs in schizophrenia.


A Bombyx homolog of ovo is a segmentation gene that acts downstream of Bm-wnt1(Bombyx wnt1 homolog).
Insect embryogenesis is divided into long and short/intermediate germ types. The long germ type may exhibit Drosophila-like hierarchical segmentation mechanisms, whereas the short/intermediate type assumes some repeating mechanisms that are considered to be ancestral. Embryogenesis in Bombyx mori possesses both characteristics. Here, Bombyx ovo homolog (Bm-ovo) was identified as a gene involved in segmentation. Ovo is a Drosophila gene that encodes a zinc finger transcription factor and studies on its homolog functions in other systems have suggested that it acts as a switch to enable the initiation of differentiation from a progenitor cell state. This is the first description for ovo homologs being involved in insect segmentation. Bm-ovo is expressed dynamically during embryogenesis in a pattern that resembles that of gap and pair-rule genes. In Bm-ovo RNAi knockdown embryos, posterior segmentation does not proceed. In addition, defects in anterior segments are observed. In Bm-wnt1 knockdown embryos, the Bm-ovo expression pattern was changed, suggesting that Bm-wnt1 is an upstream regulator of Bm-ovo. The involvement of Bm-ovo may represent a novel ancestral step under the control of wnt genes in insect segmentation: this step may resemble those operating in cell differentiation processes.


The psychosocial adjustment of patients and spouses to dialysis treatment.
Sixty-eight patients on hospital dialysis and their spouses were studied to compare their levels of adjustment and to examine gender differences. Two measures were used: BSI for psychological distress and PAIS for psychosocial adjustment to dialysis. High scores of psychological distress and adjustment problems were found both for patients and their spouses, with high correlations between the partners. Female patients and their husbands had higher scores than male patients and their wives respectively, and in some areas the husbands of female patients reported even more problems than the male patients. Clinical and theoretical conclusions are discussed.


A Chinese hamster ovary cell line hypersensitive to ionizing radiation and deficient in repair replication.
An X-ray-sensitive Chinese hamster ovary cell line was isolated by means of a semi-automated procedure in which mutagenized cells formed colonies on top of agar, were X-irradiated, and were photographed at two later times. We compared the photographs to identify colonies that displayed significant growth arrest. One of the colonies identified in this manner produced a stable line (irs1SF) that is hypersensitive to ionizing radiation. The X-ray dose at which 10% of the population survives (D10) is 2.25 Gy for irs1SF and 5.45 Gy for the parental line. The new mutant is also moderately sensitive to ethyl methanesulfonate. irs1SF performs only half as much X-ray-induced repair replication as the parental line, indicating a defect in excision repair. This defect is believed to be the primary cause of the line's radiosensitivity. Although irs1SF repairs DNA double-strand breaks at a normal rate, it repairs single-strand breaks more slowly than normal. irs1SF has an elevated number of spontaneous chromatid aberrations and produces significantly higher numbers of X-ray-induced chromatid aberrations after exposure during the G1 phase of the cell cycle. The line is hypomutable, with X-ray exposure inducing only one-third as many 6-thioguanine-resistant colonies as the parental line.


The interaction between duration, velocity and repetitive auditory stimulation.
Repetitive auditory stimulation (with click trains) and visual velocity signals both have intriguing effects on the subjective passage of time. Previous studies have established that prior presentation of auditory clicks increases the subjective duration of subsequent sensory input, and that faster moving stimuli are also judged to have been presented for longer (the time dilation effect). However, the effect of clicks on velocity estimation is unknown, and the nature of the time dilation effect remains ambiguous. Here were present a series of five experiments to explore these phenomena in more detail. Participants viewed a rightward moving grating which traveled at velocities ranging from 5 to 15°/s and which lasted for durations of 500 to 1500 ms. Gratings were preceded by clicks, silence or white noise. It was found that both clicks and higher velocities increased subjective duration. It was also found that the time dilation effect was a constant proportion of stimulus duration. This implies that faster velocity increases the rate of the pacemaker component of the internal clock. Conversely, clicks increased subjective velocity, but the magnitude of this effect was not proportional to actual velocity. Through considerations of these results, we conclude that clicks independently affect velocity and duration representations.


A covalently bound inhibitor triggers EZH2 degradation through CHIP-mediated ubiquitination.
Enhancer of zeste homolog 2 (EZH2) has been characterized as a critical oncogene and a promising drug target in human malignant tumors. The current EZH2 inhibitors strongly suppress the enhanced enzymatic function of mutant EZH2 in some lymphomas. However, the recent identification of a PRC2- and methyltransferase-independent role of EZH2 indicates that a complete suppression of all oncogenic functions of EZH2 is needed. Here, we report a unique EZH2-targeting strategy by identifying a gambogenic acid (GNA) derivative as a novel agent that specifically and covalently bound to Cys668 within the EZH2-SET domain, triggering EZH2 degradation through COOH terminus of Hsp70-interacting protein (CHIP)-mediated ubiquitination. This class of inhibitors significantly suppressed H3K27Me3 and effectively reactivated polycomb repressor complex 2 (PRC2)-silenced tumor suppressor genes. Moreover, the novel inhibitors significantly suppressed tumor growth in an EZH2-dependent manner, and tumors bearing a non-GNA-interacting C668S-EZH2 mutation exhibited resistance to the inhibitors. Together, our results identify the inhibition of the signaling pathway that governs GNA-mediated destruction of EZH2 as a promising anti-cancer strategy.


Formation factors and hazard evaluation of halogenated methyl sulfonic acid in drinking water.
Halogenated methyl sulfonic acid (HMSAs) is a new type of disinfection by-product recently reported, and there are few relevant studies, so its source and harm are still unclear. This study mainly discusses the source of halogenated methyl sulfonic acid from the macroscopic level and evaluates the harm to human health. This study clarified that chlorine disinfection is one of the main ways of generating halogenated methyl sulfonic acids (HMSAs) in drinking water. The macroscopic properties of HMSA precursors were analyzed through liquid chromatograph-mass spectrometry (LC-MS/MS), 3D fluorescence, and Fourier transform infrared spectrometry. The results showed that polar and positively charged organic compounds with molecular weights of >3 KDa or <0.5 KDa can readily generate HMSAs. By analyzing the main components of natural organic compounds in water and comparing them with the characteristics of organic compounds such as dimethyl sulfoxide and ethyl mercaptan, it meant that natural organic compounds are easily degraded. Humic and fulvic acids contribute the most to HMSA generation. This study lasted for three years and collected water samples from 102 waterworks in 24 cities in China, and the existence of HMSAs in drinking water in different cities was analyzed. The potential health risks associated with HMSAs were used by the United States Environmental Protection Agency (U.S. EPA) health risk assessment model. The average and maximum concentrations of HMSAs in tap water from key cities in China were taken as evaluation objects. The results showed that the carcinogenic risk coefficient (R) value of both concentrations was far lower than the lowest acceptable carcinogenic risk (1.0 × 10-6) provided by U.S. EPA. Therefore, HMSAs in drinking water in China currently pose no human health risks.


Biochemical analysis of cerebrum of fetal rat X-irradiated in utero--DNA, RNA, superoxide dismutase and lipid peroxide--.
Wistar rats were X-irradiated in utero and biochemical analysis of the cerebrum was performed on gestational day (g d) 21. The cerebral weight was significantly lower in the irradiated group on g d 13 with above 75R than in the control group. The contents of DNA, RNA and protein were decreased in the cerebrum of the fetuses irradiated with 100R on g d 13 when calculated per cerebrum, and DNA only was decreased occasionally when expressed as per gm wet weight. The lipid peroxide level of the cerebrum in the irradiated group was increased compared to that of the control group. The superoxide dismutase (SOD; E.C. 188.8.131.52.) activity was extremely low and lipid peroxidation in vitro was considerably enhanced in fetal cerebrum. The low activity of SOD may be one of the factors which cause the vulnerability of fetal brain to irradiation.


Cytological characteristics of cultured epithelial cells from thymomas in BUF/Mna rats.
Epithelial cells (ECs) from spontaneously developed thymomas in BUF/Mna rats were cultured, characterized and compared with ECs from normal thymuses. The ECs from thymomas had many more keratin filaments and PAS-positive vesicles in the cytoplasm than ECs from normal thymuses. The size and shape of ECs and their nuclei were heterogeneous and about 20% of ECs from thymomas had more than one nucleus. However, the growth rates and saturation densities of ECs from thymomas in monolayer culture were not markedly different from those of normal thymuses. The ECs from thymomas cultured in soft agar did not form any colonies. The distribution of the numbers of chromosomes found in ECs from thymomas was slightly broader than that in normal ECs, but no specific abnormalities nor marker chromosomes were noted. These findings indicate that ECs from thymomas are abnormal, but suggest that they are not malignant in nature.


Impregnation of Scots pine and beech with tannin solutions: effect of viscosity and wood anatomy in wood infiltration.
The impregnation process of Scots pine and beech samples with tannin solutions was investigated. The two materials involved in the process (impregnation solution and wood samples) are studied in depth. Viscosity of mimosa tannin solutions and the anatomical aspect of beech and Scots pine were analysed and correlated. The viscosity of tannin solutions presents a non-newtonian behaviour when its pH level increases, and in the case of addition of hexamine as a hardener, the crosslinking of the flavonoids turns out to be of great importance. During the impregnation of Scots pine (Pinus sylvestris L.) and beech (Fagus sylvatica L.), the liquid and solid uptakes were monitored while taking into consideration the different conditions of the impregnation process. This method allowed to identify the best conditions needed in order to get a successful preservative uptake for each wooden substrate. The penetration mechanism within the wood of both species was revealed with the aid of a microscopic analysis. Scots pine is impregnated through the tracheids in the longitudinal direction and through parenchyma rays in the radial direction, whereas in beech, the penetration occurs almost completely through longitudinal vessels.


Exploring Metastable Phases During Lithiation of Organic Battery Electrode Materials.
In this work, the Li-ion insertion mechanism in organic electrode materials is investigated through the lens of atomic-scale models based on first-principles theory. Starting with a structural analysis, the interplay of density functional theory with evolutionary and potential-mapping algorithms is used to resolve the crystal structure of the different (de)lithiated phases. These methods elucidate different lithiation reaction pathways and help to explore the formation of metastable phases and predict one- or multi-electron reactions, which are still poorly understood for organic intercalation electrodes. The cathode material dilithium 2,5-oxyterephthalate (operating at 2.6 V vs. Li/Li+) is investigated in depth as a case study, owing to its rich redox chemistry. When compared with recent experimental results, it is demonstrated that metastable phases with peculiar ring-ring molecular interactions are more likely to be controlling the redox reactions thermodynamics and consequently the battery voltage.


Laboratory dielectric measurements to evaluate the conductivity change in the presence of chelating agent with different brines.
In the oil and gas reservoirs, the interaction between the injected fluids and the reservoir fluids and rocks plays a major role in the productivity of any oil and gas field. Studying the ion exchange between reservoir fluids and the injected fluids for water flooding or chemical enhanced oil recovery purposes would help in optimizing the oil displacement process and hence the productivity form such secondary or tertiary recovery mechanisms. Chelating agents are used for enhance oil recovery to improve the oil displacement and sweep efficiency by altering the reservoir rock's surface. When it comes to fluid-rock interaction, conductivity and ionic activity of the injected water will have a great impact on the rock's surface charge and therefore in the reservoir's wettability. Dielectric laboratory measurements have the ability to observe the change in conductivity at high frequency due to the presence of free ions and salts in fluids. In this work, observing the effect of chelating agent with different salts on high frequency conductivity using laboratory dielectric measurements has been conducted. Introducing laboratory dielectric measurement could be a valuable tool in the lab as an evaluation technique into the ion exchange that occurs between different fluids from the reservoir with different brines and additives to study the fluid-fluid interaction activities. It can be also utilized to investigate the maximum chelating capacity of different chelating agents with different cations which can be reflected by the change in conductivity.


[Nutrition management of cancer patients after surgery on the esophagus and stomach: modern view on problem].
The review discusses the problem of cancer patients' nutrition, the data of the nutritional factors role in the restoring the normal functioning of the gastrointestinal tract, the basic principles of the diet after operations on the esophagus and stomach.


Short-Term Efficacy and Safety of Torasemide and Furosemide in 366 Dogs with Degenerative Mitral Valve Disease: The TEST Study.
Furosemide is the only loop diuretic recommended by the ACVIM consensus guidelines for treatment of congestive heart failure (CHF) in dogs related to degenerative mitral valve disease (DMVD). Torasemide is another potent loop diuretic with a longer half-life and a higher bioavailability. (1) To demonstrate that torasemide given once a day (q24h) is noninferior to furosemide given twice a day (q12h) for treating dogs with CHF; (2) and to compare the effect of the 2 drugs on the time to reach a composite cardiac endpoint "spontaneous cardiac death, euthanasia due to heart failure or CHF class worsening." A total of 366 dogs with CHF attributable to DMVD. Analysis of 2 prospective randomized single-blinded reference-controlled trials was performed. Dogs orally received either torasemide q24h (n = 180) or furosemide q12h (n = 186) in addition to standard CHF therapy over 3 months. The primary efficacy criterion was the percentage of dogs with treatment success assessed in each study. The time to reach the composite cardiac endpoint was used as secondary criterion in the overall population. Torasemide was noninferior to furosemide (Ptorasemide - Pfurosemide = +7%; 95% CI [-8%; +22%] and Ptorasemide - Pfurosemide = +1%; 95% CI [-12%; +14%], respectively, in Study 1 and Study 2). Torasemide (median dose = 0.24 mg/kg/d q24h; range = 0.10-0.69 mg/kg/d) was associated with a 2-fold reduction in the risk of reaching the composite cardiac endpoint (adjusted HR = 0.47; 95% CI = 0.27-0.82; P = 0.0077) as compared with furosemide (median dose = 1.39 mg/kg q12h; range = 0.70-6.30 mg/kg q12h). Torasemide q24h is an effective oral diuretic in dogs with CHF.


Recurrence of konzo in southern Tanzania: rehabilitation and prevention using the wetting method.
There have been four konzo outbreaks in Tanzania from 1985 to 2002/2003 with a total of 363 cases of konzo. Every outbreak of konzo resulted from large cyanogen intakes from bitter cassava during drought, which caused food shortages and led to people using short-cut methods of cassava processing. Rehabilitation of the 214 konzo subjects from the two most recent outbreaks of konzo in southern Tanzania was carried out by screening konzo subjects and included provision of crutches and wheel chairs. The wetting method was taught to 216 women activists from the konzo-prone villages, in the first large scale community based intervention to reduce cyanogen intake. Using cassava cyanide kits, the average total cyanide content was reduced by the wetting method about 4-fold, in agreement with previous studies. This model to help prevent konzo requires the widespread education of women activists to use the wetting method.


Protective and destructive immunity in the periodontium: Part 2--T-cell-mediated immunity in the periodontium.
Based on the results of recent research in the field and Part 1 of this article (in this issue), the present paper will discuss the protective and destructive aspects of the T-cell-mediated adaptive immunity associated with the bacterial virulent factors or antigenic determinants during periodontal pathogenesis. Attention will be focused on: (i) osteoimmunology and periodontal disease; (ii) some molecular techniques developed and applied to identify critical microbial virulence factors or antigens associated with host immunity (with Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis as the model species); and (iii) summarizing the identified virulence factors/antigens associated with periodontal immunity. Thus, further understanding of the molecular mechanisms of the host's T-cell-mediated immune responses and the critical microbial antigens related to disease pathogenesis will facilitate the development of novel therapeutics or protocols for future periodontal treatments.


Assessment of travel distance for hyperthermic intraperitoneal chemotherapy in women with ovarian cancer.
To evaluate travel distance in women with advanced or recurrent epithelial ovarian cancer (OC) undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) and the subsequent impact upon outcomes. An IRB-approved single-institution prospective registry was queried for women with OC who underwent HIPEC from 1/1/2009-12/1/2020. Demographic, oncologic, and surgical data were recorded. The patient's home zip code was compared to the institutional zip code to determine travel distance using Google Maps. Patients were divided into three strata for analysis: 1) local: ≤50 miles, 2) regional: 51-99 miles, and 3) distant: ≥100 miles and univariate analysis was performed. Of 127 women, the median distance travelled was 57.0 miles (IQR: 20.6, 84.6). There were no significant differences in mild (28.3% vs. 26.3 vs. 24.1%), moderate (21.7% vs. 15.8% vs. 17.2%) or severe postoperative complications (11.7% vs. 5.3% vs. 17.2%) (p = 0.75) for local, regional and distant patients, respectively. There was no difference in progression-free survival (17.4 vs. 22.2 vs. 12.8 months, p > 0.05) or overall survival (57.3 vs. 61.6 vs. 29.2 months, p > 0.05) for local, regional or distant patients, respectively. This study demonstrates that women with OC are willing to travel for HIPEC, with over 50% traveling > 50 miles. Our results suggest that women who travel for HIPEC procedures are not at increased risk for perioperative complications or worse oncologic outcomes than those local to HIPEC centers.


Usefulness of angiography in studying carcinoma of the bladder.
Angiography of the pelvic vasculature can be quite helpful in assessing bladder tumors, for it provides useful results both when used alone and when used in combination with other methods. It is especially useful when there is doubt about the results of simpler methods, particularly in younger patients.


Significance of magnetic resonance angiography-diffusion weighted imaging mismatch in hyperacute cerebral infarction.
Therapeutic results with respect to lesion size were analyzed and compared in patients with hyperacute cerebral infarction with and without major artery lesions on magnetic resonance angiography (MRA) and in those who did and did not receive intravenous (IV) tissue plasminogen activator (t-PA). Of the patients with cerebral infarction who visited the hospital within 3 hours of onset between April 2007 and September 2009, 127 patients with cerebral infarction in the anterior circulation region in whom head magnetic resonance imaging (diffusion-weighted imaging [DWI]) or MRA was performed (81 men and 46 women; mean age, 71 ± 11 years) were enrolled. Major artery lesions (+) were defined as internal carotid artery occlusion and middle cerebral artery (M1/M2 segment) occlusion and ≥50% stenosis. Based on the presence or absence of major artery lesions and the size of DWI lesions, the subjects were divided into 3 groups: MRA-DWI mismatch (+) group [major artery lesion (+) and DWI-ASPECTS ≥6], MRA-DWI mismatch (-) group [major artery lesion (+) and DWI-ASPECTS <6], and major artery lesion (-) group. IV t-PA was given to 21 of the 64 patients in the MRA-DWI mismatch (+) group, to 1 of the 24 patients in the MRA-DWI mismatch (-) group, and to 9 of the 39 patients in the major artery lesion (-) group. In the MRA-DWI mismatch (+) group (n = 64), the median National Institutes of Health Stroke Scale (NIHSS) score on admission was higher in t-PA-treated patients than in t-PA-untreated patients (15 vs 11). The modified Rankin scale (mRS) score at day 90 after onset was more favorable in t-PA-treated patients (0-2 in 10 patients [48%] and 3-6 in 11 patients [52%]) than in t-PA-untreated patients (0-2 in 12 patients [28%] and 3-6 in 31 patients [72%]). After adjusting for admission NIHSS score, there was a significant difference in outcome (mRS score) between t-PA-treated patients (0-2 in 10 patients [48%] and 3-6 in 11 patients [52%]) and t-PA-untreated patients (0-2 in 3 patients [9%] and 3-6 in 29 patients [91%]) (P = .002). In the MRA-DWI mismatch (-) group (n = 24), mRS scores at day 90 after onset were poor in both t-PA-treated (3-6 in 1 patient [100%]) and t-PA-untreated patients (0-2 in 1 patient [4%] and 3-6 in 22 patients [96%]). In the major artery lesion (-) group (n = 39), mRS scores at day 90 after onset were favorable in both t-PA-treated (0-2 in 9 patients [100%]) and t-PA-untreated patients (0-2 in 28 patients [93%] and 3-6 in 2 patients [7%]). When comparing major artery lesions in the MRA-DWI mismatch (+) group, outcomes were more favorable in patients with M1/M2 segment lesions who received t-PA than in those who did not receive t-PA. In the MRA-DWI mismatch (+) group, the prognosis was significantly better for t-PA-treated patients than for t-PA-untreated patients, suggesting that IV t-PA is indicated in patients with MRA-DWI mismatch.


Other genetic liver diseases in children.
Wilson disease is rare but proteiform, and should be suspected in any child with liver disease and older than 3 years of age. The treatment is very efficient, and must be taken life-long. Fifteen percent of patients with alpha-1-antitrypsin deficiency develop a neonatal jaundice, and 3% a cirrhosis in childhood. There is no specific treatment except liver transplantation. Five percent of cystic fibrosis patients develop a cirrhosis, with a very slow progression. Milder abnormalities are frequent, as well as biliary stones. Liver disease in ciliopathies may be a congenital hepatic fibrosis, with risks of portal hypertension and cholangitis, or a more variable biliary disease. Gilbert disease is frequent and benign. Crigler-Najjar syndrome is rare, severe, and may be an indication for liver or liver-cell transplantation.


The effect of recombination on the accuracy of phylogeny estimation.
Phylogenetic studies based on DNA sequences typically ignore the potential occurrence of recombination, which may produce different alignment regions with different evolutionary histories. Traditional phylogenetic methods assume that a single history underlies the data. If recombination is present, can we expect the inferred phylogeny to represent any of the underlying evolutionary histories? We examined this question by applying traditional phylogenetic reconstruction methods to simulated recombinant sequence alignments. The effect of recombination on phylogeny estimation depended on the relatedness of the sequences involved in the recombinational event and on the extent of the different regions with different phylogenetic histories. Given the topologies examined here, when the recombinational event was ancient, or when recombination occurred between closely related taxa, one of the two phylogenies underlying the data was generally inferred. In this scenario, the evolutionary history corresponding to the majority of the positions in the alignment was generally recovered. Very different results were obtained when recombination occurred recently among divergent taxa. In this case, when the recombinational breakpoint divided the alignment in two regions of similar length, a phylogeny that was different from any of the true phylogenies underlying the data was inferred.


The Role of Vasculature Engineering in Dental Pulp Regeneration.
Creating an optimal microenvironment that supports angiogenesis, cell-cell cross talk, cell migration, and differentiation is crucial for pulp/dentin regeneration. It was shown that dental stem cells being seeded onto a scaffold and transplanted in vivo could give rise to a new tissue similar to that of the native pulp. However, the unique structure of the tooth with a pulp space encased within hard dentin allows only a single blood supply from a small apical opening located at the apex of the root canals. Therefore, a further strategy that can address this limitation such as the incorporation of endothelial/endothelial progenitor cells or cells with high angiogenic potential into the transplant is required so that the added cells can contribute to the vascularization within the implant. However, the placement of 2 or more different cell types inside 3-dimensional porous scaffolds is technologically challenging. In contrast to the conventional scaffolding approach, self-assembly of monodispersed cells into 3-dimensional tissue mimics permits true physiological interactions between and among different types of cells without any influence from a secondary material. In this review, we discuss potential strategies that can be used in vasculature engineering in dental pulp regeneration with a specific emphasis on combining prevascularization and scaffold-based or scaffold-free approaches.


Pioglitazone initiation and subsequent hospitalization for congestive heart failure.
Thiazolidinediones (TZD) have been associated with an expansion in plasma volume and the development of peripheral oedema. A recent study reported an association between the use of TZDs and development of congestive heart failure (CHF). The objective of this study was to determine if short-term use of pioglitazone, a TZD, is associated with increased risk of admission to hospital because of CHF in a well-characterized, community-based cohort of Type 2 diabetic patients without prevalent CHF. A cohort study of all patients in the Kaiser Permanente Medical Care Program with Type 2 diabetes (Kaiser Permanente Northern California Diabetes Registry) who initiated any diabetes pharmacotherapy (n = 23 440) between October 1999 and November 2001. Only patients initiating single new therapies ('new users') were included to reduce confounding and create mutually exclusive exposure groups. We constructed Cox proportional hazards models (with sulphonylureas initiators specified as the reference group) to evaluate the impact of initiating new diabetes therapies on time-to-incident admission to hospital because of CHF, defined by primary hospital discharge diagnosis. Patients initiated pioglitazone (15.2%), sulphonylureas (25.3%), metformin (50.9%), and insulin (8.6%) alone, or as additions to pre-existing or maintained therapies. Three hundred and twenty admissions for CHF were observed during the follow-up (mean 10.2 months) after drug initiation. Relative to patients initiating sulphonylureas, there were no significant increases in the incidence of hospitalization for CHF in those initiating pioglitazone [hazard ratio (HR) = 1.28; 95% confidence interval (CI): 0.85-1.92] after adjusting for demographic, behavioural and clinical factors. There was a significantly higher incidence among those initiating insulin (HR = 1.56; 95% CI: 1.00-2.45) and lower incidence among those initiating metformin (HR = 0.70; 95% CI: 0.49-0.99). This study of patients with Type 2 diabetes failed to find evidence that short-term pioglitazone use was associated with an elevated risk of hospitalization for CHF relative to the standard, first-line diabetes therapy.


Development and evaluation of a standardized technique to assess teat skin temperature of dairy cows using infrared thermography.
Much research has been done to develop methods to assess dimensional teat traits in dairy cows. In contrast, diagnostic techniques to reliably assess the circulatory system of teats are limited. Infrared thermography facilitates measurements of skin temperature and could be used to detect physiological and pathological changes to the teat tissue associated with machine milking, as temperature reflects the underlying blood circulation and tissue metabolism. Our objective was to develop and evaluate a scanning technique to quantify teat skin temperature in dairy cows using infrared thermography. Using a portable thermography camera, 2 operators obtained duplicate scans of both hind teats from 20 Holstein cows, resulting in 80 thermographic images (20 cows × 2 operators × 2 images). Average teat skin temperatures at the proximal, middle, and distal teat aspects were determined. We used Pearson correlation coefficients (r), intraclass correlation coefficients (ICC), and concordance correlation coefficients (CCC) to assess interoperator reproducibility (i.e., agreement between measurements performed by different operators) and intraoperator repeatability (i.e., agreement between measurements performed by the same operator). Pearson correlation coefficients revealed a very strong correlation for measurements at the proximal, middle, and distal aspects of the teat, respectively, between operators (r ≥0.95) and duplicate scans (r ≥0.94) within operators. Intraclass correlation coefficients and CCC indicated excellent interoperator reproducibility (ICC ≥0.95, CCC ≥0.95) and excellent intraoperator repeatability (ICC ≥0.94, CCC ≥0.94), respectively, for measurements at all 3 aspects. Least squares means (95% confidence interval) for average teat skin temperatures at the proximal, middle, and distal teat aspects, respectively, were 33.2 (32.6-33.8), 32.4 (31.5-33.2), and 30.9 (29.8-32.0) °C for operator 1, and 33.2 (32.6-33.8), 32.4 (31.6-33.3), and 31.0 (29.9-32.0) °C for operator 2. Average temperatures between duplicate scans within operators at the proximal, middle, and distal aspects, respectively, were 33.3 (32.7-33.9), 32.5 (31.7-33.3), and 31.0 (29.9-32.1) °C for the first scan and 33.2 (32.6-33.8), 32.3 (31.5-33.1), and 30.8 (29.7-31.9) °C for the second scan. We conclude that infrared thermography facilitates precise measurements of skin temperatures of cows' hind teats.


Update on genetics of parkinsonism.
Major progress in genetic studies of Parkinson's disease (PD) and parkinsonism has been achieved in the last two decades. We provide a brief review of the current status of PARK and non-PARK loci/genes, and discuss two new genes: eIF4G1 and VPS35. The literature on PARK and non-PARK loci/genes was reviewed and some novel information on two new genes is provided. There are 18 PARK loci. The symptomatic carriers of these genes usually present with parkinsonism, although additional clinical features can be seen during the course of the disease. Carriers of non-PARK loci/genes frequently present with a mixed phenotype that includes parkinsonism and additional clinical features. Carriers of the eIF4G1 and VPS35 genes present with a parkinsonian phenotype. The pathology of eIF4G1 is of the α-synuclein type; the pathology of VPS35 is unknown. The current genetic classification of PD/parkinsonism genes is not ideal. The pathological classification based on the accumulation of particular proteins/inclusions is also misleading since there are kindred with a single mutation but pleomorphic pathology. A better classification of neurodegenerative conditions is needed. It is hoped that the genetic studies will lead to better therapies.


Association between dental infections and the clinical course of chronic liver disease.
Dental infections are implicated in several systemic diseases due to bacteremia and pro-inflammatory effects, but their possible role in liver disease is unclear. We retrospectively analyzed the clinical course of liver disease in relation to dental health among 116 patients with liver cirrhosis who underwent dental examination before liver transplantation. The need for multiple tooth extractions, a surrogate marker of dental infections, was associated with reduced time from diagnosis of liver disease to the need for liver transplantation (P = 0.02). The association was independent of age, sex, liver disease etiology and Model for End-Stage Liver Disease (MELD) score (P = 0.04). Among 38 patients with accurate laboratory follow-up data, the number of tooth extractions correlated with the change in MELD score during the year preceding dental examination (r = 0.43, P = 0.03). Spontaneous bacterial peritonitis caused by Streptococcus viridans occurred only among patients with multiple dental infections. Dental infections may influence the clinical course of liver disease, but prospective studies are needed.


Validation of the analysis of the 15+1 European-priority polycyclic aromatic hydrocarbons by donnor-acceptor complex chromatography and high-performance liquid chromatography-ultraviolet/fluorescence detection.
The European Commission recommends to monitor the 16 polycyclic aromatic hydrocarbons (PAHs) possessing both genotoxic and carcinogenic properties. Since robust analytical methods specific for this set of European PAH are lacking, a new method for their analysis in food is proposed. The donnor-acceptor complex chromatography (DACC) is used as clean-up step and high-performance liquid chromatography-ultraviolet/fluorescence detection (HPLC-UV/FLD) is used for detection and quantification. The method has been validated for analysis of PAH in oil and in dried plants and bears very good results for all compounds.


A hybrid-capture approach to reconstruct the phylogeny of Scleractinia (Cnidaria: Hexacorallia).
A well-supported evolutionary tree representing most major lineages of scleractinian corals is in sight with the development and application of phylogenomic approaches. Specifically, hybrid-capture techniques are shedding light on the evolution and systematics of corals. Here, we reconstructed a broad phylogeny of Scleractinia to test previous phylogenetic hypotheses inferred from a few molecular markers, in particular, the relationships among major scleractinian families and genera, and to identify clades that require further research. We analysed 449 nuclear loci from 422 corals, comprising 266 species spanning 26 families, combining data across whole genomes, transcriptomes, hybrid capture and low-coverage sequencing to reconstruct the largest phylogenomic tree of scleractinians to date. Due to the large number of loci and data completeness (less than 38% missing data), node supports were high across shallow and deep nodes with incongruences observed in only a few shallow nodes. The "Robust" and "Complex" clades were recovered unequivocally, and our analyses confirmed that Micrabaciidae Vaughan, 1905 is sister to the "Robust" clade, transforming our understanding of the "Basal" clade. Several families remain polyphyletic in our phylogeny, including Deltocyathiidae Kitahara, Cairns, Stolarski & Miller, 2012, Caryophylliidae Dana, 1846, and Coscinaraeidae Benzoni, Arrigoni, Stefani & Stolarski, 2012, and we hereby formally proposed the family name Pachyseridae Benzoni & Hoeksema to accommodate Pachyseris Milne Edwards & Haime, 1849, which is phylogenetically distinct from Agariciidae Gray, 1847. Results also revealed species misidentifications and inconsistencies within morphologically complex clades, such as Acropora Oken, 1815 and Platygyra Ehrenberg, 1834, underscoring the need for reference skeletal material and topotypes, as well as the importance of detailed taxonomic work. The approach and findings here provide much promise for further stabilising the topology of the scleractinian tree of life and advancing our understanding of coral evolution.


Endobronchial valves in the management of broncho-pleural and alveolo-pleural fistulae.
Pneumothorax from bronchopleural or alveolo-pleural fistulae can be complicated by prolonged air leak (AL). This can occur in a variety of clinical settings. Examples include structural lung disease, such as bronchiectasis, and cavitary lung disorders. Prolonged AL is associated with prolonged hospital stay, atelectasis, pneumonia, and thromboembolic disease. Endobronchial valves (EBVs) have been recently introduced to manage such situations. The global experience in this novel therapeutic modality is still evolving. We report our preliminary experience with managing persistent AL treated successfully with EBVs and review the current literature on this subject. Our experience shows that EBVs are an effective tool for the management of prolonged AL from persistent bronchopleural or alveolo-pleural fistulae. It is a minimally invasive procedure recommended as an option, particularly in patients not fit for surgical repair.


Top-down influences on visual processing.
Re-entrant or feedback pathways between cortical areas carry rich and varied information about behavioural context, including attention, expectation, perceptual tasks, working memory and motor commands. Neurons receiving such inputs effectively function as adaptive processors that are able to assume different functional states according to the task being executed. Recent data suggest that the selection of particular inputs, representing different components of an association field, enable neurons to take on different functional roles. In this Review, we discuss the various top-down influences exerted on the visual cortical pathways and highlight the dynamic nature of the receptive field, which allows neurons to carry information that is relevant to the current perceptual demands.


Impact of the COVID-19 lockdown on typical ambient air pollutants: Cyclical response to anthropogenic emission reduction.
Preliminary studies have confirmed that ambient air pollutant concentrations are significantly influenced by the COVID-19 lockdown measures, but little attention focus on the long term impacts of human countermeasures in cities all over the world during the period. Still, fewer have addressed their other essential properties, especially the cyclical response to concentration reduction. This paper aims to fill the gaps with combined methods of abrupt change test and wavelet analysis, research areas were made of five cities, Wuhan, Changchun, Shanghai, Shenzhen and Chengdu, in China. Abrupt changes in contaminant concentrations commonly occurred in the year prior to the outbreak. The lockdown has almost no effect on the short cycle below 30 d (days) for both pollutants, and a negligible impact on the cycle above 30 d. PM2.5 (fine particulate matter) has a stable short-cycle nature, which is greatly influenced by anthropogenic emissions. The analysis revealed that the sensitivity of PM2.5 to climate is increased along with the concentrations of PM2.5 were decreasing by the times when above the threshold (30-50 μg m-3), and which could lead to PM2.5 advancement relative to the ozone phase over a period of 60 d after the epidemic. These results suggest that the epidemic may have had an impact earlier than when it was known. And significant reductions in anthropogenic emissions have little impact on the cyclic nature of pollutants, but may alter the inter-pollutant phase differences during the study period.


Anomalous origins of left anterior descending and circumflex coronary arteries from separate orifices in the right coronary sinus.
A case is described of a 69-year-old man with angina pectoris who was found at coronary angiography to have all three coronary arteries arising by separate orifices from the right coronary sinus. This appears to be a previously unreported anomaly. The embryological origin and mechanisms of angina in coronary arterial anomalies are discussed.


Tai Chi as a complementary exercise for pulmonary rehabilitation in chronic obstructive pulmonary disease: A randomised controlled trial.
With the characteristics of mindfulness and breathing techniques, Tai Chi has been recommended with therapeutic values in chronic obstructive pulmonary disease (COPD). However, its strengths as a complementary exercise for conventional pulmonary rehabilitation (PR) remain unclear. This single-blinded randomised controlled trial recruited patients with mild to severe stable COPD. Eligible participants were randomly assigned to the group with usual care (control), total body recumbent stepper (TBRS) exercise, Tai Chi (TC), or combined TBRS exercise and Tai Chi (TBRS-TC). Patients received a two-month hospital-based supervised exercise, followed by a ten-month community- or home-based rehabilitation program. A total of 120 participants were recruited, and 102 were included in the per-protocol analysis. The mean changes in St George's Respiratory Questionnaire (SGRQ) total score from baseline to the post-hospital exercise in the control group, TBRS group, TC group, and TBRS-TC group was 2.62 (95 % CI -8.99 to 8.99), -9.28 (95 % CI -13.96 to -4.60), -10.19 (95 % CI -13.72 to -6.67), and -16.75 (95 % CI -20.25 to -13.24), respectively, with a statistically significant difference between groups in favor of the TBRS-TC exercise (P < 0.001). The remarkable effect of TBRS-TC exercise in improving the quality of life maintained until the end of the community- or home-based rehabilitation training (P < 0.001). Besides, a statistically better effect with the TBRS-TC exercise was also observed in the outcomes regarding exercise capacity, pulmonary function, symptom burden, and systemic inflammation after the whole process of 12-month integrative PR exercise programme. Based on the results, a novel integrated exercise modality combining Tai Chi and conventional pulmonary rehabilitation was developed. It might contribute to more positive effects in patients with stable COPD. The study was registered with the Chinese Clinical Trial Registry (ChiCTR-IOR-15006874) prior to commencing recruitment.


Epidural analgesia and anesthesia in dogs and cats.
Current knowledge of drugs administered epidurally has allowed an effective way of providing analgesia for a wide variety of conditions in veterinary patients. Proper selection of drugs and dosages can result in analgesia of specific segments of the spinal cord with minimal side effects. Epidural anesthesia is an alternative to general anesthesia with inhalation anesthetics, although the combination of both techniques is more common and allows for reduced doses of drugs used with each technique. Epidural anesthesia and intravenous anesthetics can also be used without inhalation anesthetics in surgical procedures caudal to the diaphragm.


Nuclear control of neurite induction in neuroblastoma cells.
Induction of neurite formation in neuroblastoma cells by dibutyryl cyclic 3':5'-AMP (db-cAMP) or prostaglandin EI (PGE1) was enhanced after enucleation. Cells selected for resistance to db-cAMP were induced to form neurites by db-cAMP or PGE1 only after, but not before enucleation. Inhibition of protein synthesis inhibited neurite induction in nucleated, but not in enucleated cells, and enucleated cells were less sensitive to inhibition of neurite formation by concanavalin A (ConA). Colchicine, vinblastine and cytochalasin B (CB), compounds that interfere with the assembly of microtubules and microfilaments, inhibited induction in both types of cells. It is suggested that enucleation removes a nuclear inhibitor of neurite induction by db-cAMP and PGE1, and that neurite induction in nucleated cells requires that cAMP activates the assembly of microtubules and microfilaments and inactivates the nuclear inhibitor.


The contribution of Portuguese nursing to universal health access and coverage.
to analyze the contribution of Portuguese nursing to improving universal health access and coverage by means of the identification of nurses in the health system; evolution of health indicators; and access-promoting systems, in which nurses play a relevant role. this was documentary research of publications from national and international organizations on planning and health outcomes. Statistical databases and legislation on health reforms were consulted. nurses represent 30.18% of human resources in the national health service; the systems of access promotion performed by nurses have good levels of efficacy (95.5%) and user satisfaction (99% completely satisfied); in the local care the creation of Community Care Units (185) occurred, and 85.80% of home consultations were performed by nurses. political strategies, the National Health Service and strengthening of human resources in healthcare are the main determinants. Nursing is the most numerous professional group in the National Health Service, however numbers remain deficient in primary health care. The improvement of academic qualification and self-regulation of this professional group has allowed for better answers in improving health for the Portuguese.


Increase in differentiated type of T lineage cells in the myasthenic thymus: two-color fluorocytometric analysis.
We made use of two-color flow cytometry to examine thymic lymphoid cells from patients with myasthenia gravis. The CD4+CD8- cells and the CD4-CD8+ cells were significantly increased in the thymus from the patients, compared with findings in the control samples. Conversely, the CD4+CD8+ cells were significantly decreased. Significant increases in CD1-CD3+ cells and significant decreases in CD1+CD3- cells were noted. The percentage of CD45R+ cells also increased. There were no increases in activated T lymphocytes, defined as CD4+DR+ cells, CD8+DR+ cells, or IL2R+ cells. We conclude that the proportion of T lineage lymphocytes that are differentiated is increased in the thymus of patients with myasthenia gravis, and could reflect accelerated differentiation.


Inhibition of inflammatory cell-mediated myelin oxidation and interleukin-1 beta generation by a 21-aminosteroid, U74500A.
Inflammatory cell-mediated myelin injury may be an important cause of tissue damage in both acute and chronic central nervous system (CNS) disorders. The 21-aminosteroids are novel derivatives of methylprednisolone without obvious glucocorticoid or mineralocorticoid side effects. We evaluated the ability of 21-aminosteroid, U74500A, to inhibit oxidation of rat brain myelin by human polymorphonuclear leukocytes (PMN) and monocytes. Myelin samples, as confirmed by SDS-PAGE, were incubated with PMN or monocytes and 100 microM U74500A or vehicle. Myelin oxidation by both PMN and monocytes was significantly reduced by U74500A. These observations demonstrate that U74500A can inhibit myelin oxidation by inflammatory cells. Additionally, 100 microM U74500A significantly reduced production of interleukin 1-beta by monocytes exposed to myelin. The aminosteroids may be beneficial in CNS disorders where myelin injury by inflammatory cells appears to contribute, such as acute focal ischemia or multiple sclerosis.


Repression of the Antioxidant NRF2 Pathway in Premature Aging.
Hutchinson-Gilford progeria syndrome (HGPS) is a rare, invariably fatal premature aging disorder. The disease is caused by constitutive production of progerin, a mutant form of the nuclear architectural protein lamin A, leading, through unknown mechanisms, to diverse morphological, epigenetic, and genomic damage and to mesenchymal stem cell (MSC) attrition in vivo. Using a high-throughput siRNA screen, we identify the NRF2 antioxidant pathway as a driver mechanism in HGPS. Progerin sequesters NRF2 and thereby causes its subnuclear mislocalization, resulting in impaired NRF2 transcriptional activity and consequently increased chronic oxidative stress. Suppressed NRF2 activity or increased oxidative stress is sufficient to recapitulate HGPS aging defects, whereas reactivation of NRF2 activity in HGPS patient cells reverses progerin-associated nuclear aging defects and restores in vivo viability of MSCs in an animal model. These findings identify repression of the NRF2-mediated antioxidative response as a key contributor to the premature aging phenotype.


The effects of high pass filters on computer-reconstructed evoked potentials.
The effects of high pass filters with cut-off frequencies of 160 and 320 Hz on computer-constructed potentials with known parameters were studied. It is concluded that high pass filtering using high cut-off frequencies introduces temporal and amplitude distortions and artefacts which may not be distinguished from true potentials.


A rapid method for isolation of the plasma membrane of the myxamoebae and swarm cells of the myxomycete Didymium iridis.
A method for the isolation of the plasma membranes of the acellular slime mould, Didymium iridis in the myxamoebae and swarm cell stages was developed using a modified dextranpolyethylene glycol aqueous two-phase polymer system. It was found to be far superior to the widely accepted technique of density gradient centrifugation concerning this cellular system. Chemical and enzymatic assays performed on the plasma membranes and other cell fractions as well as microscopic examination were used as a basis for positive identification and assessment of purity. Results of the chemical and enzymatic assays indicate that plasma membranes are recovered with high yield and purity using the modified two-phase polymer technique. The method is both rapid and effective and can be performed using low-speed centrifugation.


Thromboxane modulating agents. 4. Design and synthesis of 3-(2-[[(4-chlorophenyl)sulfonyl]-amino]ethyl)benzenepropanoic acid derivatives as potent thromboxane receptor antagonists.
The design of a series of thromboxane receptor antagonists based on 3-(2-[[(4-chlorophenyl)sulfonyl]amino]ethyl)benzenepropanoic acid (1) is described. Addition of an arylmethyl group at the 5-position of 1 gave exceptionally potent agents in vitro and in vivo, with 13a (UK-147,535) giving complete blockade of the TxA2 receptor for greater than 12 hours in dogs, following an oral dose of 0.1 mg/kg.


The prognostic impact of inflammatory factors in patients with multiple myeloma treated with thalidomide in Korea.
The purpose of this study was to determine the correlations between inflammatory factors-including absolute lymphocyte count, lactate dehydrogenase, β2-microglobulin, albumin, C-reactive protein, and ferritin-and the prognosis for survival in patients with multiple myeloma (MM) treated with induction chemotherapy containing thalidomide and who underwent autologous stem cell transplantation (ASCT). Data from patients at 13 university hospitals in South Korea were collected retrospectively between December 2005 and May 2013. The median age of the 232 patients was 57 years (range, 33 to 77) and the male to female ratio was 1.09:1. In the multivariate analysis, fewer than two combined abnormal inflammatory factors was the only independent prognostic factor for superior progression-free survival (relative risk [RR], 0.618; 95% confidence interval [CI], 0.409 to 0.933; p = 0.022), and platelet count > 100 × 10(9)/L and fewer than two combined abnormal inflammatory factors were independent prognostic factors for superior overall survival (RR, 4.739; 95% CI, 1.897 to 11.839; p = 0.001 and RR, 0.263; 95% CI, 0.113 to 0.612; p = 0.002, respectively). Patients with two or more than two combined inflammatory factors who were treated with thalidomide induction chemotherapy and who underwent ASCT showed significantly shorter survival compared to those with fewer than two combined inflammatory factors. These results could be helpful for predicting prognosis in patients with MM.


Probiotics, prebiotics and synbiotics improved the functionality of aquafeed: Upgrading growth, reproduction, immunity and disease resistance in fish.
Aquaculture plays an increasingly significant role in improving the sustainability of global fish production. This sector has been intensified with the advent of new husbandry practices and the development of new technology. However, the increasing intensification and indiscriminate commercialized farming has enhanced the vulnerability of cultivated aquatic species to damage from pathogens. In efforts to confront these various diseases, frequent use of drugs, antibiotics, chemotherapeutics, and agents for sterilization have unintentionally added to the risk of transmission of pathogens and harmful chemical compounds to consumers. Some natural dietary supplements are believed to have the potential to offset this setback in aquaculture. Application of bio-friendly feed additives such as probiotics, prebiotics and synbiotics are becoming popular dietary supplements with the potential to not only improve growth performance, but in some cases can also enhance immune competence and the overall well-being of fish and crustaceans. The present review discusses and summarizes the effects of probiotics, prebiotics and synbiotics application on growth, stress mitigation, microbial composition of intestine, immune system and health condition of aquatic animals in association with existing constraints and future perspectives in aquaculture.


In-vivo job development training among peer providers of homeless veterans supported employment programs.
This column describes a goal-oriented, time-limited in vivo coaching/training approach for skills building among peer veterans vocational rehabilitation specialists of the Homeless Veteran Supported Employment Program (HVSEP). Planning, implementing, and evaluating the training approach for peer providers was intended, ultimately, to support veterans in their goal of returning to community competitive employment. The description draws from the training experience that aimed to improve the ability of peer providers to increase both rates of employment and wages of the homeless veterans using their services. Training peers using an in vivo training approach provided a unique opportunity for the veterans to improve their job development skills with a focus to support employment outcomes for the service users. Peers who received training also expressed that learning skills through an in vivo training approach was more engaging than typical classroom trainings. (PsycINFO Database Record


Evaluation of the interchangeability between the new fully-automated affinity chrome-mediated immunoassay (ACMIA) and the Quantitative Microsphere System (QMS) with a CE-IVD-certified LC-MS/MS assay for therapeutic drug monitoring of everolimus after solid organ transplantation.
This study aims to evaluate the interchangeability between the Siemens Healthineers' "EVRO" new affinity chrome-mediated immunoassay (ACMIA/EVRO) and Thermo Fisher Scientific's "EVER" Quantitative Microsphere System (QMS/EVER) with Chromsystems' CE-IVD-certified "MassTox" liquid-chromatography/tandem-mass spectrometry (LC-MS/MS) assay for the therapeutic drug monitoring of everolimus. A single lot of reagent, calibrators and controls were used for each assay. A total of 67 whole blood samples (n=67) from patients receiving solid organ transplant were analyzed (n=31 with kidney transplant and n=36 with liver transplant); Passing-Bablok regression and Bland-Altman difference plot were used to evaluate bias and individual agreement; LC-MS/MS analysis was used to measure the actual concentrations of calibrators and controls compared to the assigned value. ACMIA/EVRO did not show any systematic bias compared to LC-MS/MS (intercept=0.244 ng/mL, 95% CI: -0.254 to 0.651 ng/mL). Nevertheless, significant proportional bias (slope=1.511, 95% CI: 1.420 to 1.619) associated to a combined bias of 44.8% (95% CI: 41.2-48.3%) was observed. Conversely, QMS/EVER did not show any bias at both systematic (intercept=-0.151 ng/mL, 95% CI: -0.671 to 0.256 ng/mL) and proportional level (slope=0.971, 95% CI: 0.895 to 1.074) with a non-statistically significant combined bias of -3.6% (95% CI: -8.4-1.1%). Based on a concentration of calibrators and controls above the assigned value for both the analytical methods, in the ACMIA/EVRO a correction which was approximately one-third of the correction for the QMS/EVER was observed. ACMIA/EVRO but not QMS/EVER shows a lack of interchangeability with the CE-IVD-certified LC-MS/MS assay. We hypothesize that, as the ACMIA/EVRO uses an anti-sirolimus antibody, the under-corrected assigned value in the assay calibrators was not sufficient to reproduce the everolimus metabolites cross-reactivity occurring in real samples.


From strict moral standards to ethical neutrality: a policy-guided shift in the patentability of human embryonic stem cells in China.
Attitudes towards human embryonic stem cells (hESCs) in China have witnessed a significant shift in 2020 that can be attributed to China's policy guidance. For ethical reasons, stricter standards are adopted to curb related regulations and patent licensing. Through the introduction of policies, some research on hESCs has been recognized as legitimate and feasible to a certain standard and scope. In the subsequent practice of patent examination, the dual influence of policy support and public interest has led to a shift in the examination standards of China's intellectual property authority from "strict morality" to "ethical neutrality", implying limited recognition of hESCs' patentability. In view of the promotion of policy incentives for the transformation and application of corresponding research, there is considerable social demand to provide patent protection for research results. In this context, an adjustment of related regulations is illustrated in this revision, manifesting a partial shift in regulations towards a supportive stance consistent with policy.


Lipid peroxidation and endothelial cell injury: implications in atherosclerosis.
Vascular endothelial cells, which play an active role in the physiological processes of vessel tone regulation and vascular permeability, form a border separating deeper layers of the blood vessel wall and cellular interstitial space from the blood and circulating cells. Damage or dysfunction of endothelial cells may reduce the effectiveness of the endothelium to act as a selectively permeable barrier to plasma components, including cholesterol-rich lipoprotein remnants. This may be involved in the etiology of atherosclerosis. Experimental evidence indicates that free radical-mediated lipid peroxidation can induce endothelial cell injury/dysfunction. Reactive oxygen species, including peroxidized lipids capable of initiating cell injury, may be generated within endothelial cells, be present in plasma components, or be derived from neutrophils or other blood-borne cells. Lipid peroxidation could initiate or promote the process of atherosclerotic lesion formation by directly damaging endothelial cells, and by enhancing the adhesion and activation of neutrophils and the susceptibility of platelets to aggregate. Endothelial cell injury by lipid hydroperoxides also could increase the uptake of LDL into the vessel wall. These events and other cellular dysfunctions may individually or collectively initiate and/or help to sustain the development of atherosclerosis.


Environmental consequences of a power plant shut-down: a three-dimensional water quality model of Dublin Bay.
A hydro-environmental model is used to investigate the effect of cessation of thermal discharges from a power plant on the bathing water quality of Dublin Bay. Before closing down, cooling water from the plant was mixed with sewage effluent prior to its discharge, creating a warmer, less-saline buoyant pollutant plume that adversely affects the water quality of Dublin Bay. The model, calibrated to data from the period prior to the power-plant shut-down (Scenario1), assessed the water quality following its shut-down under two scenarios; (i) Scenario2: continued abstraction of water to dilute sewage effluents before discharge, and (ii) Scnenario3: sewage effluents are discharged directly into the Estuary. Comparison between scenarios was based on distribution of Escherichia coli (E. coli), a main bathing quality indicator. Scenarios1 and 2, showed almost similar E. coli distribution patterns while Scenario3 displayed significantly higher E. coli concentrations due to the increased stratification caused by the lack of prior dilution.


Combined Anti-Biofilm Enzymes Strengthen the Eradicate Effect of Vibrio parahaemolyticus Biofilm: Mechanism on cpsA-J Expression and Application on Different Carriers.
Vibrio parahaemolyticus is a human foodborne pathogen, and it can form a mature biofilm on food and food contact surfaces to enhance their resistance to antibacterial agents. In this study, the effect of anti-biofilm enzymes (combined lipase, cellulase and proteinase K) on the inhibition and eradication of pathogen biofilm was evaluated. The biofilm content of V. parahaemolyticus showed the highest level at the incubation time of 24 h, and the combined enzymes significantly inhibited the biofilm's development. The biofilm's inhibition and eradication rate at an incubation time of 24 h was 89.7% and 66.9%, respectively. The confocal laser scanning microscopic images confirmed that the microcolonies' aggregation and the adhesion of biofilm were inhibited with the combined enzyme treatment. Furthermore, combined enzymes also decreased the concentration of exopolysaccharide (EPS) and disrupted the EPS matrix network, wherein the expression of the EPS-related gene, cpsA-J, was likewise suppressed. The combined enzymes showed an excellent inhibition effect of V. parahaemolyticus biofilm on different carriers, with the highest inhibition rate of 59.35% on nonrust steel plate. This study demonstrates that the combined enzyme of lipase, cellulase and proteinase K could be a novel candidate to overcome biofilm's problem of foodborne pathogens in the food industry.


Investigating anticipatory processes during sequentially changing reward prospect: An ERP study.
Performance-contingent reward prospect modulates the stability-flexibility balance in voluntary task switching. High reward prospect typically increases stability, indicated by a low voluntary switch rate (VSR). But this effect depends on the immediate reward history: Only when a high reward repeats (reward remains high), stability is increased. In contrast, when reward increases (high reward following low reward) cognitive flexibility is promoted, indicated by a relatively high VSR. To investigate the underlying mechanisms of changing reward expectations during voluntary task choice, we conducted two experiments and measured reward cue-locked event-related potentials (P2, P3b, CNV). The experiments yielded consistent findings: The P2 was stronger in response to high vs. low reward reflecting an early attentional boost by high reward anticipation. The P3b was highest in increase, intermediate in remain-high, and lowest in low reward trials suggesting responsiveness to working memory updating and motivational arousal. Finally, the CNV increased over time and was sensitive to both reward magnitude and sequence with the lowest amplitude in reward remain-low trials suggesting that preparatory control only increases when worth the effort. Taken together, early attentional processes (P2) were boosted by mere reward magnitude, while later processes (P3b, CNV) were sensitive to both reward magnitude and its sequence.


Gold-195m for serial first pass radionuclide angiocardiography during upright exercise in patients with coronary artery disease.
Sequential first pass radionuclide angiocardiography can be performed in rapid succession using gold-195m because of its low radiation dose and short half-life (30.5 seconds). In 25 patients with known or suspected coronary artery disease, first pass studies with gold-195m were obtained using a computerized multicrystal gamma camera at rest (n = 29), at the end of each 3 minute stage of exercise (n = 25) and immediately after exercise (n = 23). In 13 patients, assessment of left ventricular function during exercise with gold-195m was combined with thallium-201 stress scintigraphy. Left ventricular ejection fraction at rest assessed with technetium-99m and gold-195m correlated well (r = 0.93). In addition, repeat left ventricular ejection fractions at rest with gold-195m correlated closely (r = 0.96). Comparing peak exercise left ventricular ejection fraction with ejection fraction at rest, abnormal left ventricular reserve was found in 20 of 25 patients. Various abnormal patterns of left ventricular ejection fraction response were noted, showing the diagnostic potential of serial exercise angiocardiography. Thallium-201 myocardial images, obtained on a single crystal gamma camera after multiple gold-195m injections, were all of good diagnostic quality and were abnormal in 10 of 13 patients. Thus, multiple high count rate first pass studies can be obtained with gold-195m during and after exercise, allowing serial study of physiologic changes in left ventricular function during exercise. Thallium-201 myocardial imaging can be performed using the same exercise test, providing direct comparison of myocardial function and perfusion.


Aspirin-induced heat stress resistance in chicken myocardial cells can be suppressed by BAPTA-AM in vitro.
Our recent studies have displayed the protective functions of aspirin against heat stress (HS) in chicken myocardial cells, and it may be associated with heat shock proteins (HSPs). In this study, we further investigated the potential role of HSPs in the aspirin-induced heat stress resistance. Four of the most important HSPs including HspB1 (Hsp27), Hsp60, Hsp70, and Hsp90 were induced by aspirin pretreatment and were suppressed by BAPTA-AM. When HSPs were induced by aspirin, much slighter HS injury was detected. But more serious damages were observed when HSPs were suppressed by BAPTA-AM than those cells exposed to HS without BAPTA-AM, even the myocardial cells have been treated with aspirin in prior. Comparing to other HSPs, HspB1 presented the largest increase after aspirin treatments, 86-fold higher than the baseline (the level before HS). These findings suggested that multiple HSPs participated in aspirin's anti-heat stress function but HspB1 may contribute the most. Interestingly, during the experiments, we also found that apoptosis rate as well as the oxidative stress indicators (T-SOD and MDA) was not consistently responding to heat stress injury as expected. By selecting from a series of candidates, myocardial cell damage-related enzymes (CK-MB and LDH), cytopathological tests, and necrosis rate (measured by flow cytometry assays) are believed to be reliable indicators to evaluate heat stress injury in chicken's myocardial cells and they will be used in our further investigations.