Ascorbic acid deficiency and hepatic UDP-glucuronyl transferase. Qualitative and quantitative differences.
The effect of dietary ascorbate on hepatic UDP glucuronyltransferase (UDPGT) appears to be selective in that only certain isozymes of UDPGT are jeopardized. In this study, ascorbic acid deficiency produced a 68% reduction in the specific activity of hepatic UDPGT towards p-nitrophenol. Earlier studies showed a reduction in UDPGT activity towards p-aminophenol in ascorbate-deficient guinea pigs, whereas bilirubin and acetaminophen glucuronidation were unaffected. Kinetic studies suggest that p-aminophenol and p-nitrophenol are metabolized by a single isozyme in that p-nitrophenol was found to be a competitive inhibitor of p-aminophenol glucuronidation. Both qualitative and quantitative studies on partially purified UDPGT from ascorbate-deficient and ascorbate-supplemented guinea pigs were carried out to investigate the biochemical role of the vitamin. Qualitative differences were observed in UDPGT from ascorbate-deficient animals and included an increased lability to: thermal inactivation; storage at 4 degrees; and purification with UDP-glucuronic acid agarose column chromatography. Furthermore, an analysis of the microsomal membrane showed a 14% increase in membrane fluidity in ascorbate deficiency. Ascorbic acid added in vitro could not reverse the increase in fluidity observed in ascorbate-deficient microsomal membranes; however, ascorbylpalmitate, a more lipophilic form of the vitamin, was effective. Palmitic acid had no effect on membrane fluidity in microsomes from either the ascorbate-supplemented or ascorbate-deficient animals. This increase in membrane fluidity could not be explained by differences in cholesterol, total phospholipid, or phosphatidylcholine content of hepatic microsomes. Furthermore, a quantitative reduction in UDPGT partially purified from ascorbate-deficient guinea pigs was indicated by a marked reduction in protein banding at 55,000 daltons when compared to UDPGT partially purified from ascorbate-supplemented animals.


The outer membrane protein of Fusobacterium necrophorum, 43K OMP, stimulates inflammatory cytokine production through nuclear factor kappa B activation.
Fusobacterium necrophorum causes bovine hepatic abscess, foot rot, mastitis, and endometritis. The 43 kDa outer membrane protein (43 K OMP) of F. necrophorum is a porin protein that plays an important role in infections by this bacterium, but the biological function and the pathogenesis of this protein are largely unknown. In this study, we investigated the role of the 43 K OMP in bacterial infection of bovine mammary epithelial cells (MAC-T cells) by Tandem Mass Tag proteomic analysis. The RAW264.7 cells were incubated with recombinant 43 K OMP (12.5 μg/mL) for 2 h, 4 h, 6 h, and 12 h, and then the inflammatory related protein and inflammatory cytokine production were measured by Western blot analysis and ELISA, the mRNA expression levels of inflammatory cytokine were measured by Real-Time PCR. Proteomic analysis results demonstrated there were 224 differentially expressed proteins in the MAC-T cells stimulated with the 43 K OMP compared with control, and 118 proteins were upregulated and 106 proteins were downregulated. These differentially expressed proteins were mainly involved in NF-kappa B signaling, bacterial invasion of epithelial cells, cell adhesion, complement and coagulation cascades. The top six differentially expressed proteins were; MMP9, PLAU, STOM, PSMD13, PLAUR, and ITGAV, which were involved in a protein-protein interaction network. Furthermore, TLR/MyD88/NF-κB pathway related proteins and inflammatory cytokines (IL-6, TNF-α, and IL-1β) were assessed by Western blot analysis and ELISA. Results showed the 43 K OMP to enhance the expression of TLR4 protein at 2 h (P < 0.01) and the MyD88 protein at 4 h (P < 0.05) post-stimulation, and to decrease IκBα expression at 4 h, 6 h and 12 h (P < 0.05) post-infection, as well as induce phosphorylation at Ser536 (P < 0.01). Levels of IL-6, IL-1β, and TNF-α in the supernatants of mouse macrophages were increased (P < 0.05), as were mRNA expression levels of IL-6, IL-1β, and TNF-α (P < 0.05), while IL-4 mRNA expression was decreased (P < 0.05). Taken together, these results suggested the important role for 43 K OMP in F. necrophorum infection, promoting the production of pro-inflammatory cytokines (IL-6 and TNF-α) by activation of the TLR/MyD88/NF-κB pathway. These findings provided a theoretical basis for a better understanding of the pathogenesis of F. necrophorum infection.


Effectiveness of a collaborative diabetes screening campaign between community pharmacies and general practitioners.
To evaluate the impact of a collaborative screening campaign on the prevalence of pre-diabetes and diabetes among the screened population. A Longitudinal, multicentre study was developed. The Finnish Diabetes Risk Score (FINDRISC) was applied to the eligible population in the participating community pharmacies. Individuals with a FINDRISC score ≥ 15, were eligible to measure their glycated haemoglobin (HbA1c) level at the community pharmacy. If HbA1c≥ 5.7%, participants were referred to a general practitioner (GP) appointment for potential diagnosis of Diabetes. Out of 909 screened subjects, 405 (44.6%) presented a FINDRISC score ≥ 15. Among the latter, 94 (23.4%) had HbA1c levels that made them eligible for GP referral, of which 35 (37.2%) completed the scheduled appointments. 24 participants were diagnosed with pre-diabetes, and 11 with diabetes. The prevalence was estimated at 2.5% (CI95% 1.6-3.8%) and 7.8% (CI95% 6.2-9.8%) for diabetes and pre-diabetes, respectively. This collaborative model has proved to be effective in the early detection of diabetes and pre-diabetes. Joint initiatives between health professionals can play a pivotal role in the prevention and diagnosis of diabetes, which may lead to a reduction on the burden to health system and society.


Amino acid analysis by gas-liquid chromatography of N-heptafluorobutyryl isobutyl esters. Complete resolution using a support-coated open-tubular capillary column.
Amino acids have been separated by gas-liquid chromatography as their N-heptafluorobutyryl isobutyl esters. Complete resolution of derivatives of all the common amino acids has been achieved using a high-performance support-coated open-tubular capillary column. The analysis time was 30 min. Modifications to the derivatization procedure of MacKenzie and Tenaschuk have been introduced. Acylation by heating at 150 degrees was shown to be destructive; 110 degrees has been selected for routine preparation. To obtain a volatile histidine derivative it has been found necessary to add an antioxidant and to heat samples with ethoxyformic anhydride prior to injection. Amino acid analysis of beta-lactoglobulin after 6 N HCl digestion yielded results in good agreement with those obtained by the conventional ion-exchange method. The method has also been successfully applied to estimation of the different caseins in whole casein and in purified fractions by amino acid analysis of residues liberated by carboxy-peptidase digestion.


Genetic characterization and molecular mapping of a chlorophyll deficiency gene in sunflower (Helianthus annuus).
A major gene controlling chlorophyll deficiency (phenotyped by yellow leaf color, yl) in sunflower was identified and mapped in an F(2) population derived from a cross between two breeding lines. Greenness degree was scored by a hand-held chlorophyll meter in the F(2) population. Leaf tissue from the parents, F(1) hybrids, and some F(2) progenies were also sampled to determine the chlorophyll content. All F(1) plants had normal green leaf color and the segregation of the plants in the F(2) population fits the monogenic ratio (chi((3:1))(2)=0.03, p>0.9), indicating that leaf color is a monogenic trait with normal green dominant over yellow leaf color in this population. The contents of chlorophyll a, chlorophyll b, and total chlorophyll in the yellow-leafed lines were reduced by 41.6%, 53.5%, and 44.3%, respectively, in comparison with those in the green-leafed lines. Genetic mapping with molecular markers positioned the gene, yl, to linkage group 10 of sunflower. An SSR marker, ORS 595, cosegregated with yl, and a TRAP marker, B26P17ga5-300, was linked to yl with a genetic distance of 4.2cM. The molecular marker tightly linked to the chlorophyll deficiency gene will provide insight into the process of chlorophyll metabolism in sunflower.


Stimulation of human lymphocytes by cytomegalovirions and dense bodies.
Lymphocytes from healthy adult individuals were examined for their ability to incorporate thymidine in the presence of cytomegalovirus (CMV) and dense bodies. It was found that lymphocytes from donors with antibodies to CMV were stimulated to incorporate thymidine-14C both by preparation of CMV and CMV dense bodies. Lymphocytes from CMV seronegative donors did not respond. Dilution experiments and the dose-response curve indicate that the stimulation induced by the dense body preparation was not caused by the small amounts of contaminating CMV particles. These results indicate that in healthy human adults there is a correlation between CMV seropositivity and in vitro lymphocyte transformation, induced by either CMV or by dense bodies.


Ramp rate of blood pressure changes does not affect aortic afferent sensitivity in anesthetized rats.
To investigate whether the rate of change in blood pressure affects the sensitivity of the aortic baroreceptor afferent response, the change in aortic nerve activity (ANA) to two different rates of ramp increase in mean blood pressure (MBP), elicited by phenylephrine administration, was determined in the rat under urethane (1.5 g kg(-1)) anesthesia. The sensitivity of the increase in ANA following a rapid (average ramp rate, 9.14+/-0.60 mm Hg s(-1), n=11) or gradual (1.78+/-0.24 mm Hg s(-1), n=11) increase in MBP was 2.03+/-0.14% and 1.81+/-0.20% of baseline mm Hg(-1), respectively. These values were not significantly different from each other (P=0.16). Furthermore, we found no correlation between the rate of ramp increase in MBP and the sensitivity of the increase in ANA (r=0.24, P=0.29, n=22). These results suggest that, at least within the normal physiological range of MBP, the rate of the ramp change in blood pressure does not affect aortic baroreceptor afferent sensitivity in the anesthetized rat.


Relation of CD4+CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease.
Allergic diseases are frequent and rising in prevalence, and result from activation of T-helper (Th) 2 cells by allergens. CD4+CD25+ regulatory T cells suppress T-cell activation in vitro and prevent pathological findings in animal models of disease. We aimed to investigate whether the amount of inhibition of allergic responses by CD4+CD25+ T cells was related to atopy and allergic disease. Blood CD4+CD25+ and CD4+CD25- T cells were isolated from three groups of donors: non-atopic individuals; those atopic with no present symptoms; and patients with hayfever studied during and out of the grass-pollen season. We investigated the ability of CD25+ T cells from these donors to suppress allergen-stimulated T-cell proliferation and cytokine production in vitro. CD4+CD25+ T cells from non-atopic donors suppressed proliferation and interleukin 5 production by their own allergen-stimulated CD4+CD25- T cells. Inhibition of proliferation by CD4+CD25+ T cells from atopic donors was significantly reduced (p=0.0012), and was even more diminished by CD4+CD25+ T cells isolated from patients with hayfever during the pollen season (p=0.0003). In patients with hayfever, out-of-season suppression remained less than that seen by regulatory cells from non-atopic donors. Allergic disease can result from an inappropriate balance between allergen activation of regulatory CD4+CD25+ T cells and effector Th2 cells. This imbalance could result from a deficiency in suppression by regulatory T cells or strong activation signals could overcome such regulation. Treatment to enhance regulatory T-cell responses, in concert with reduction of Th2 cell activation, might be useful in prevention and treatment of allergic disease.


[Recombinase Polymerase Amplification for Rapid Detection of Human Bacterial Pneumonia Pathogens].
A diagnostic system based on recombinase polymerase amplification (RPA) has been developed to identify six bacterial pathogens of human pneumonia. Species-specific primers have been designed and optimized to conduct a multiplex reaction in one common volume. Labeled primers were used for reliable discrimination of amplification products that are similar in size. Identification of the pathogen was carried out by visual analysis of an electrophoregram. The analytical sensitivity of the developed multiplex RPA was 10^(2)-10^(3) copies of DNA. The specificity of the system was determined by the absence of cross-amplification of the studied DNA samples of pneumonia pathogens for each pair of primers, as well as for the DNA of Mycobacterium tuberculosis H37rv, and amounted to 100%. The execution time of the analysis is less than an 1 h, including the electrophoretic reaction control. The test system can be used in specialized clinical laboratories for rapid analysis of samples from patients with suspected pneumonia.


Trajectories of Benzodiazepine Use among Older Adults from a Concordance-with-Guidelines Perspective: A Nationwide Cohort Study.
Benzodiazepines (including zolpidem and zopiclone) are often associated with higher-than-recommended intake and durations of use, especially in older adults. The objective of this study was to characterize trajectories of benzodiazepine use according to recommended patterns in older adults, and to assess predictors of the risk of developing each of these trajectories. Using the French Health Insurance database, we constituted a cohort of adults aged ≥ 65 years who initiated benzodiazepines in 2007 and were followed for up to 8 years. Concordance with benzodiazepine use guidelines was assessed on a quarterly basis according to a "concordance-with-guideline score" with values 1-5. Group-based trajectory modeling was then applied as implemented in the Proc Traj procedure in SAS to define guideline-concordant trajectories based on seven baseline patient-centered characteristics: sex, complementary health insurance coverage, treated alcohol and tobacco use disorder, polypharmacy, hospital stay, and registered chronic diseases. Among 5080 new users (64.1% women, median age 74 years), six trajectories of benzodiazepine use were identified. Three, representing 70% of users, were concordant with guidelines, whereas three implied non-concordant benzodiazepine use for part or all of the benzodiazepine use follow-up. Polymedicated patients were more prone to develop chronic non-guideline-concordant initially guideline-concordant use, whereas those with a history of long-term disease and hospitalization were more likely to develop chronic non-guideline-concordant use. The number of prescribers during the first quarter, number of daily defined doses, use of loperamide, and use of psychostimulants were associated with a higher risk of developing an initial and persistent non-guideline-concordant use. Treatment initiation by a psychiatrist, initial use of World Health Organization (WHO) step-2 opioids and non-benzodiazepine anxiolytics or sedatives were associated with a higher risk of late non-guideline-concordant use. Concordance with guidelines varied over time during benzodiazepine use in older adults. A third of these adults will hypothetically follow one of the identified non-guideline-concordant trajectories, consisting of initial and/or late non-guideline concordance. This was associated with modifiable and nonmodifiable factors that clinicians should be aware of for tailoring the monitoring of patients.


The transverse outer preputial (TOP) island flap: an easy method to cover urethroplasties and skin defects in hypospadias repair.
The transverse outer preputial (TOP) island flap, a simple procedure inspired by the double-faced island flap, is proposed as a substitute for the Byars repair to provide skin coverage for most of the current reconstructive techniques for hypospadias. From 1996 to 2003, 108 consecutive children (aged 1-8 years) had a primary repair of various forms of hypospadias with different degrees of chordee; the TOP island flap was used in 66. The surgical technique is based on the use of a dorsal transverse skin flap mobilized with its own vascular pedicle from the outer foreskin, then ventrally rotated longitudinally after removing the inner part of the prepuce. Partial necrosis of the lateral border of the flap was infrequent (<2%) and did not induce urethral complications. There was no total necrosis in the series. The rate of fistula was comparable with children operated using other techniques (8%). The cosmesis was good, with no ventral bulkiness or hypertrophic scarring. The TOP island flap is a safe method for covering a new urethra and penile skin defects, with good cosmetic results.


Weighing in on monkeypox against the criteria of public health emergency.
The monkeypox, a viral zoonotic disease usually found in forest areas of Central and Western Africa, has spread worldwide through new modes of transmission little understood. The WHO on 23 July 2022, declared the virus a Public Health Emergency of International Concern (PHEIC).The declaration has stirred criticism from leading scientists that the criteria for PHEIC as defined by International Health Regulation have not been met and it is non-transparent and contradictory. This paper reviews the criteria of PHEIC and weighs the rationales behind the declaration to increase the clarity of the WHO's decision, justifications, and legitimacy in the ongoing outbreak.


The utility of prostate-specific antigen velocity thresholds in clinical practice: a population-based analysis.
To investigate the ability of prostate-specific antigen velocity (PSAV) to predict prostate cancer, and assess the test characteristics of several PSAV thresholds for identifying prostate cancer and high-grade cancers. From a population-based database of PSA results, men with an initial PSA level of <10.0 ng/mL, taken between I January 1994 and 31 December 2003, were identified. Those with three or more PSA tests before diagnosis, taken over > or =18 months, were included. Men were followed for a diagnosis of prostate cancer or histologically confirmed benign disease until 31 December 2003. In all, 24 709 men were included, with 716 (2.9%) diagnosed with prostate cancer and 1488 (6.0%) with benign histology. The mean (10.38 vs 0.43 ng/mL/year) and median (1.47 vs 0.03 ng/mL/year) PSAV were considerably higher in men with prostate cancer than in those with no cancer (P < 0.001). There was no PSAV threshold that could reliably identify prostate cancer or high-grade cancers without requiring many men to proceed to prostate biopsy. In this population, PSAV had additional value over one PSA value in identifying men with prostate cancer. Many men with prostate cancer might have a 'normal' (<0.75 ng/mL/year) PSAV. As with total PSA level, there was no PSAV threshold that could reliably predict prostate cancer, but rather a continuum of risk of cancer associated with PSAV level.


Update on the Management of Chronic Total Occlusions in Coronary Artery Disease.
Chronic total occlusions (CTOs) are found in about a third of patients with coronary artery disease (CAD) and can pose a significant challenge during percutaneous revascularization. However, advances in CTO percutaneous coronary intervention (PCI) strategies, devices, and algorithms have led to significant improvements in successful treatment of CTOs. This review summarizes current management of CTOs in the context of modern PCI techniques and current evidence. The hybrid algorithm now provides a standardized, teachable approach to CTO PCI, and success rates are approximately 90% in experienced hands. The first randomized controlled trial in patients with CTOs recently reported that patients with ST elevation myocardial infarction (STEMI) and a CTO in the non-culprit vessel showed an improvement in ejection fraction in patients undergoing CTO PCI of the LAD, but not other vessels. Updated data from the SYNTAX trial showed a benefit with complete revascularization in patients with coronary artery disease (CAD). Incomplete revascularization of CTOs in the PCI group may explain some of the benefit seen with CABG over PCI in patients with complex coronary disease. Contemporary CTO registries have reported success rates of approximately 90%, and the OPEN-CTO registry updates our understanding of CTO PCI complication rates and outcomes. The available evidence highlights the potential benefits of CTO PCI in patients with an indication for revascularization. Technological advancements have paved the way for success rates approaching 90% at high-volume centers, but further studies evaluating outcomes following CTO PCI are needed, with several currently underway.


The food plant preferences of Phratora vitellinae (Coleoptera: Chrysomelidae) : A. Field observations.
In the Upper Rhine (Petite Camargue, Saint Louis, France) study site, Ph. vitellinae are found mainly on Salix nigricans on which they are bivoltine. Some beetles are occasionally observed on S. purpurea, especially in Spring, but never on S. alba, S. caprea and S. cinerea. In other European localities, S. nigricans or S. hegetschweileri at higher elevations are frequently recorded as host-plants. However, some populations are also found on S. purpurea, P. tremula and P. trichocarpa x deltoïdes, usually when neither S. nigricans nor S. hegetschweileri are present.All the Salicaceae on which Ph. vitellinae was observed in the field have leaves rich in phenylglycosides and with glabrous lower surfaces, at least in Spring. Ph. vitellinae was never recorded on those Salix species with leaf undersurfaces densely covered with trichomes.At the time of emergence of the beetles from hibernation, S. nigricans leaves are more developed than those of S. purpurea and S. cinerea. Moreover, those S. nigricans trees with the longer shoots in Spring support the largest number of beetles at their emergence. The preference of Ph. vitellinae for S. nigricans might be reinforced by these plenological differences.In the Petite Camargue, the same S. nigricans trees support the largest populations of beetles from one generation to the next and from year to year. This suggests that S. nigricans does not respond to defoliation with induced resistance to the beetles.All shoots on the branch seem to be equally suitable and attractive for oviposition. The older leaves at the base of the shoot and the younger ones at the top are less favored by ovipositing females. Survival of the egg batches and the groups of freshly emerged larvae is lower on the distal shoots of the branch and on the younger leaves. This might be due to a higher degree of exposure to predators.


[Demonstration of immune complexes on erythrocytes by scanning electron microscopy].
If anti-sera are combined with native whole blood by an in-vitro technique, immunocomplexes are formed. They are fixed to erythrocytes and can be made visible by a scanning electron microscope on blood smears especially pretreated.


Patient-Reported Outcome Measures of Quality of Life in People Affected by Diabetic Foot: A Psychometric Systematic Review.
This psychometric systematic review aimed to identify the most suitable patient-reported outcome measures (PROMs) of quality of life (QoL) in people affected by diabetic foot. We performed a literature search in MEDLINE (PubMed), CINAHL (EBSCOhost), and PsycINFO (EBSCOhost) databases from inception to February 1, 2022. We also searched gray literature databases. Eligible studies were full-text reports developing a QoL condition-specific PROM or assessing one or more of its measurement properties in people affected by diabetic foot. We assessed the methodological quality of included studies independently using the "Consensus-Based Standards for the Selection of Health Measurement Instruments Risk of Bias" checklist. The measurement properties were evaluated using specific criteria. We graded the quality of the evidence using a "Grading of Recommendations Assessment, Development and Evaluation" approach modified by Consensus-Based Standards for the Selection of Health Measurement Instruments. Forty-three reports (46 studies) providing information on the measurement properties of 10 different PROMs were included. We did not identify any instruments that could be recommended for use. We identified 2 PROMs that were not recommended for use and 8 that were potentially recommended but would require further investigation. Of these 8 PROMs, 4 had better evidence for content validity. Available PROMs to measure QoL in people affected by diabetic foot have limited evidence for their measurement properties. There is no fully suitable PROM. Pending further evidence, 4 PROMs could potentially be recommended for use.


Pupillary assessment and computational modeling of the Stroop task in depression.
Depressed individuals frequently display disruptions in selective attention, but the time course and specificity of these difficulties are not well-understood. To better understand the nature of attentional disruptions in depression, 28 healthy adults and 23 unmedicated depressed adults completed a Stroop color-naming task using a long inter-stimulus interval and pupil dilation was recorded as a measure of cognitive load. Both groups took longer to name the color for incongruent than congruent trials. Pupil dilation was also larger for incongruent trials than for congruent trials across groups, which suggested that pupil dilation reflected cognitive load on the task. Though the groups did not differ in the magnitude of Stroop effect in pupil dilation, depressed individuals displayed decreased pupil dilation in the seconds following stimuli relative to controls. Computational neural network modeling further suggested that observed effects were consistent with decreased prefrontal cortex activity, associated with decreased cognitive control.


Cytotoxic activities of trichothecenes isolated from an endophytic fungus belonging to order Hypocreales.
Bioassay-guided fractionation of the extract of the endophytic fungus KLAR 5 belonging to order Hypocreales, which was isolated from the twig of Knema laurina (Blume) Warb., resulted in the isolation of brefeldin A (1), 8-deoxy-trichothecin (2), trichothecolone (3), 7alpha-hydroxytrichodermol (4), and 7alpha-hydroxyscirpene (5). Compound 5 was isolated from natural source for the first time. Compound 1 was very highly active against human epidermoid carcinoma of the mouth, human breast cancer (BC-1), and human small cell lung cancer (NCI-H187) cells whereas compounds 2 and 4 were selectively active against BC-1 and NCI-H187 cells. Compounds 3 and 5 were moderately active against these three cancer cell lines.


The objectivity illusion and voter polarization in the 2016 presidential election.
Two studies conducted during the 2016 presidential campaign examined the dynamics of the objectivity illusion, the belief that the views of "my side" are objective while the views of the opposing side are the product of bias. In the first, a three-stage longitudinal study spanning the presidential debates, supporters of the two candidates exhibited a large and generally symmetrical tendency to rate supporters of the candidate they personally favored as more influenced by appropriate (i.e., "normative") considerations, and less influenced by various sources of bias than supporters of the opposing candidate. This study broke new ground by demonstrating that the degree to which partisans displayed the objectivity illusion predicted subsequent bias in their perception of debate performance and polarization in their political attitudes over time, as well as closed-mindedness and antipathy toward political adversaries. These associations, furthermore, remained significant even after controlling for baseline levels of partisanship. A second study conducted 2 d before the election showed similar perceptions of objectivity versus bias in ratings of blog authors favoring the candidate participants personally supported or opposed. These ratings were again associated with polarization and, additionally, with the willingness to characterize supporters of the opposing candidate as evil and likely to commit acts of terrorism. At a time of particular political division and distrust in America, these findings point to the exacerbating role played by the illusion of objectivity.


Probiotic Formulations: A Patent Landscaping Using the Text Mining Approach.
The outstanding research outcomes and registrations of myriads of probiotic strains have flooded the health market with various innovative probiotic-based products and their patents. The study of patented formulations of probiotics can give an overall insight into its existing application. A landscaping review of patents for probiotic-based preparations is presented in the current work. The patent search was performed over commercially available patent databased and analysis tool-PatSeer Pro®. Search strings containing words "Formulation" and "Composition" resulted in more than 3700 patents. Landscaping review of 400 + patents from the last 20 years (2000-2020) was performed using the Text-Mining approach. Text-Mining helped to identify 19 technological clusters which represent these patents. These clusters include the patents of probiotic preparations on animal feed, human food, cosmetics, antimicrobial, antidiabetic, arthritis, etc. A review of this massive number of patents unveiled many exciting preparations. Probiotic-based innovative products for depression, diabetes, Parkinson's, tumor, acne, and animal husbandry are reviewed comprehensively. The present work also unravels a few new-flanged products like probiotic layered condoms, products for acute alcoholism, and traditional Chinese medicine with probiotics. The patent landscape of probiotic-based preparations has presented a whole scenario of probiotic-based preparations. It has also revealed many unexplored areas where innovation can be excelled.


Temporal dynamics of learning-promoted synaptic diversity in CA1 pyramidal neurons.
Although contextual learning requires plasticity at both excitatory and inhibitory (E/I) synapses in cornu ammonis 1 (CA1) neurons, the temporal dynamics across the neuronal population are poorly understood. Using an inhibitory avoidance task, we analyzed the dynamic changes in learning-induced E/I synaptic plasticity. The training strengthened GABAA receptor-mediated synapses within 1 min, peaked at 10 min, and lasted for over 60 min. The intracellular loop (Ser408-409) of GABAA receptor β3 subunit was also phosphorylated within 1 min of training. As the results of strengthening of α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor-mediated synapses, CA1 pyramidal neurons exhibited broad diversity of E/I synaptic currents within 5 min. Moreover, presynaptic glutamate release probability at basal dendrites also increased within 5 min. To further quantify the diversified E/I synaptic currents, we calculated self-entropy (bit) for individual neurons. The neurons showed individual levels of the parameter, which rapidly increased within 1 min of training and maintained for over 60 min. These results suggest that learning-induced synaptic plasticity is critical immediately following encoding rather than during the retrieval phase of the learning. Understanding the temporal dynamics along with the quantification of synaptic diversity would be necessary to identify a failure point for learning-promoted plasticity in cognitive disorders.-Sakimoto, Y., Kida, H., Mitsushima, D. Temporal dynamics of learning-promoted synaptic diversity in CA1 pyramidal neurons.


Raptor breeding sites indicate high plant biodiversity in urban ecosystems.
Preserving biodiversity in urban ecosystems has become an urgent conservation priority, given the rapid upsurge in global urbanization. As woody plants play essential ecological roles and provide psychological benefits to human city dwellers, their preservation is of particular interest to conservation scientists. However, considering that extensive censuses of woody plants are resource-intensive, a key accomplishment is to find reliable conservation proxies that can be quickly used to locate biologically diverse areas. Here, we test the idea that sites occupied by apex predators can indicate high overall biodiversity, including high diversity of woody plants. To this end, we surveyed woody plant species within 500 m of Northern Goshawk (Accipiter gentilis) breeding sites in urban ecosystems of Japan and compared them with non-breeding control sites without goshawks. We found that goshawks successfully identified and signposted high levels of richness, abundance, and diversity of woody plants. Our findings show that sites occupied by top predatory species could be exploited as conservation proxies for high plant diversity. Due to their exigent ecological requirements, we would expect apex predators to be tied to high biodiversity levels in many other urban ecosystems worldwide.


Comprehensive analysis of synonymous codon usage patterns in orf3 gene of porcine epidemic diarrhea virus in China.
The ORF3 protein of porcine epidemic diarrhea virus (PEDV) is found to function as an ion channel which influences virus virulence and production. Taking consideration of the importance of PEDV orf3 gene, we have performed comprehensive analysis to investigate its synonymous codon usage patterns. In this study, the results of base composition analysis showed A/T rich and G/C poor in PEDV orf3 genes, and the most abundant base was nucleotide T. The relative synonymous codon usage value in each codon revealed that codon usage bias existed. The mean ENC value of each gene was 48.75, indicating a low codon usage bias, as well as a relatively instable change in PEDV orf3 genes. The general correlation analysis between base composition and codon usage bias indicated that mutational bias has an impact on the PEDV codon usage bias. Neutral analysis suggested that natural selection pressure takes a more important influence than mutational bias in shaping codon usage bias. Moreover, other factors including hydrophobicity and aromaticity have been also found to influence the codon usage variation among the PEDV orf3 genes. This study not only represents the most systematic analysis of codon usage patterns in PEDV orf3 genes, but also provides a basic shaping mechanism of the codon usage bias.


Investigating different approaches to develop informative priors in hierarchical Bayesian safety performance functions.
The Bayesian inference method has been frequently adopted to develop safety performance functions. One advantage of the Bayesian inference is that prior information for the independent variables can be included in the inference procedures. However, there are few studies that discussed how to formulate informative priors for the independent variables and evaluated the effects of incorporating informative priors in developing safety performance functions. This paper addresses this deficiency by introducing four approaches of developing informative priors for the independent variables based on historical data and expert experience. Merits of these informative priors have been tested along with two types of Bayesian hierarchical models (Poisson-gamma and Poisson-lognormal models). Deviance information criterion (DIC), R-square values, and coefficients of variance for the estimations were utilized as evaluation measures to select the best model(s). Comparison across the models indicated that the Poisson-gamma model is superior with a better model fit and it is much more robust with the informative priors. Moreover, the two-stage Bayesian updating informative priors provided the best goodness-of-fit and coefficient estimation accuracies. Furthermore, informative priors for the inverse dispersion parameter have also been introduced and tested. Different types of informative priors' effects on the model estimations and goodness-of-fit have been compared and concluded. Finally, based on the results, recommendations for future research topics and study applications have been made.


Thrombocytopenia associated with chlorpromazine, haloperidol and thiothixene: a case report.
Hematological side effects of neuroleptic drugs occur infrequently but remain a potential cause of serious toxicity. A case of recurrent thrombocytopenia due to the repeated exposure to chlorpromazine (twice), haloperidol (four times) and thiothixene (twice) in a 59 year old female treated for schizophrenia is reported. Treatment difficulties and implications of this case are discussed.


The association of physician-specialty density and melanoma prognosis in the United States, 1988 to 1993.
Studies suggest physician workforce may influence cancer outcomes. We sought to quantify the effect of physician-specialty density on melanoma prognosis. Data from 17,702 melanoma cases reported to the Surveillance, Epidemiology, and End Results program from 1988 to 1993 were merged with sociodemographic data (1990 US Census) and dermatologist, family practitioner, and internist density data (Area Resource File). Linear and logistic regression analyses were used to model prognosis (melanoma mortality to incidence ratio). A higher density of dermatologists was associated with better prognosis (lower mortality to incidence ratio) (beta = -50 x 10(-4); SE 8 x 10(-4)). Internist density was also a significant predictor of better prognosis whereas increased family practitioner density was associated with worse prognosis. Controlling for sociodemographics, physician density remained a significant predictor of the mortality to incidence ratio. Socioeconomic factors were estimated. Physician density was examined by county. Controlling for sociodemographic factors, physician-specialty density predicted melanoma prognosis. This suggests that specialist health care availability may affect melanoma outcomes.


Allotypic determinants (Igh-3) associated with the IgG2c subclass of rat immunoglobulins.
Rat antibodies to group A streptococcal carbohydrate are primarily of the IgM and IgG isotypes. Hyperimmunization often results in antibodies of a restricted molecular heterogeneity of the IgG2c isotype. An allotypic marker, designated Igh-3a, was detected on the heavy chains of the IgG2c isotype from Copenhagen rats. Igh-3b was detected on the heavy chains of IgG2c from SHR rats. A strain distribution of the Igh-3 determinants as well as inheritance patterns for their expression are presented.


Transitory block of the arachnoid granulations following subarachnoid haemorrhage. A postmortem study.
The arachnoid granulations of the superior sagittal sinus were examined for blockage by erythrocytes in 43 cases of subarachnoid haemorrhage. Ten cases had survived for more than two weeks after the haemorrhage. Among 33 cases with acute haemorrhage, 17 had evidence of blocking of the granulations. The severity of the block varied from complete clogging of nearly all granulations to slight filling of a few of them. Cases with some days' survival showed evidence of phagocytosis of the entrapped erythrocytes by macrophages. Several of the cases with old haemorrhage had groups of haemosiderin macrophages in the granulations but none showed fibrosis (except for one single villus). It is concluded that clogging of the arachnoid granulations may contribute to the raised intracranial pressure in some cases of acute subarachnoid haemorrhage. However, the observations do not support the hypothesis that the haemorrhage may lead to fibrosis or scarring of the granulations with chronic impairment of the cerebrospinal fluid resorption and subsequent hydrocephalus.


Increased aqueous lactate dehydrogenase in Coats' disease.
A 3-year-old boy had glaucoma and a total left retinal detachment that displayed peripheral intraretinal telangiectasis. The most probable clinical diagnosis was Coats' disease. A suspicion of retinoblastoma also existed, and an aqueous aspirate was assayed for lactate dehydrogenase (LDH) and found to contain three times the level present in a matching sample of serum. We enucleated the eye and verified the diagnosis of Coats' disease pathologically. The results of aqueous LDH determinations in eyes with glaucoma, phthisis, or large numbers of histiocytes, erythrocytes, and polymorphonuclear leukocytes should be interpreted with caution.


Growth potential of the transplanted lung in the infant primate.
Success in neonatal lung transplantation depends on the growth of the transplanted lung. To study the effects of transplantation and denervation on primate lung growth without rejection or immunosuppression, an autotransplant model was chosen. Eight-week-old baboons underwent left lung autotransplantation (n = 5) or sham operation (n = 1). At age 13 weeks and 9 months, single lung volumes were calculated by nitrogen washout and computed tomography. Results were compared with those of 4 unoperated weight-matched controls (2 per age group). Over the growth period, mean total lung capacity in operated baboons increased 82% (137 to 249 mL) by nitrogen washout and 70% (182 to 309 mL) by computed tomography compared with 85% (128 to 237 mL) and 74% (141 to 245 mL) for the sham-operated baboon, respectively. Transplanted left lung volume increased 91% (53 to 101 mL) by nitrogen washout and 75% (68 to 119 mL) by computed tomography compared with 85% (54 to 100 mL) and 80% (56 to 101 mL) for the sham-operated baboon, respectively. In the absence of rejection and immunosuppression, normal volume growth occurs in the transplanted infant primate lung.


Electroencephalographic slowdowns during sleep are associated with cognitive impairment in patients who have obstructive sleep apnea but no dementia.
To research the relationship between quantitative electroencephalogram (qEEG) and impaired cognitive function patients who have obstructive sleep apnea (OSA) but no dementia. Subjects who complained of snoring between March 2020 and April 2021 in the Sleep Medicine Center of Weihai Municipal Hospital were included. All subjects underwent overnight in-laboratory polysomnography (PSG) and were assessed using a neuropsychological scale. Standard fast fourier transform (FFT) was used to obtain the electroencephalogram (EEG) power spectral density curve, and to calculate the delta, theta, alpha, and beta relative power and the ratio between slow and fast frequencies. Binary logistic regression was used to assess the risk factors for cognitive impairment in patients who had OSA but no dementia. Correlation analysis was performed to determine the relationship between qEEG and cognitive impairment. A total of 175 participants without dementia who met the inclusion criteria were included in this study. There were 137 patients with OSA, including 76 with mild cognitive impairment (OSA + MCI), 61 without mild cognitive impairment (OSA-MCI), and 38 participants without OSA (non-OSA). The relative theta power in the frontal lobe in stage 2 of non-rapid eye movement sleep (NREM 2) in OSA + MCI was higher than that in OSA-MCI (P = 0.038) and non-OSA (P = 0.018). Pearson correlation analysis showed that the relative theta power in the frontal lobe in NREM 2 was negatively correlated with Mini-Mental State Examination (MMSE) scores, Montreal Cognitive Assessment (MoCA) Beijing version scores, and MoCA subdomains scores (visual executive function, naming, attention, language, abstraction, delayed recall and orientation) outside language. In patients who had OSA but no dementia, the EEG slower frequency power increased. The relative theta power in the frontal lobe in NREM 2 was associated with MCI of patients with OSA. These results suggest that the slowing of theta activity may be one of the neurophysiological changes in the early stage of cognitive impairment in patients with OSA.


Relationships of behavioral measures of frontal lobe dysfunction with underlying electrophysiology in cocaine-dependent patients.
Despite evidence that frontal lobe functioning is impaired in cocaine-dependent individuals, relationships between behavioral measures of frontal dysfunction and electrophysiological measures of inhibition in cocaine use have not been explored. Using the Frontal Systems Behavior Scale (FrSBe), frontal dysfunction was assessed in a group of abstinent cocaine-dependent subjects (N = 49) and healthy controls (N = 32). Using transcranial magnetic stimulation (TMS) and evoked potential (EP)-based electrophysiological measures of inhibition, we assessed associations between these measures and FrSBe estimates of frontal dysfunction. Patients had significantly higher FrSBe scores for executive dysfunction, disinhibition, and apathy than controls. Lower TMS-based resting motor thresholds (ie, hyperexcitability) were significantly associated with higher executive dysfunction scores in the patients. Relationships between FrSBe scores and TMS-based measures highlight neurophysiological aberrations underlying frontal lobe dysfunction in cocaine abusers. TMS and EP measures may be useful probes of the intermediary steps between frontal lobe dysfunction and addictive behavior.


Reactions of gold(III) ions with ribonuclease A and methionine derivatives in aqueous solution.
1. Addition of Au(III) (as chloroaurate) to folded ribonuclease A causes the formation of aggregates, as shown by chromatography and extreme broadening of the 270 MHZ 1H NMR spectrum. 2. When RNAase is partially unfolded Au(III) causes oxidation of methionines to the sulphoxide, and leads to almost complete unfolding (at molar equivalent ratios). 3. Reactions between model methionine derivatives and Au(III) show that the oxidation involves the production of Au(I)-methionine species. The stability of these complexes is dependent on the availability of free NH2 groups which catalyse their disproportionation.


Systemic Pharmacokinetics of Oxaliplatin After Intraperitoneal Administration by Electrostatic Pressurized Intraperitoneal Aerosol Chemotherapy (ePIPAC) in Patients with Unresectable Colorectal Peritoneal Metastases in the CRC-PIPAC Trial.
Electrostatic pressurized intraperitoneal aerosol chemotherapy (ePIPAC) is a palliative treatment for unresectable peritoneal metastases from various primary cancers. However, little is known about the systemic pharmacokinetics of oxaliplatin after ePIPAC. Twenty patients with unresectable colorectal peritoneal metastases were treated with repetitive ePIPAC monotherapy with oxaliplatin (92 mg/m2) and a simultaneous intravenous bolus of leucovorin (20 mg/m2) and 5-fluorouracil (400 mg/m2). Samples were collected during each ePIPAC: whole blood at t = 0, t = 5, t = 10, t = 20, t = 30, t = 60, t = 120, t = 240, t = 360 and t = 1080 min for plasma and plasma ultrafiltrate concentrations; urine at t = 0, t = 1, t = 3, t = 5 and t = 7 days. Samples were analyzed using atomic absorption spectrometry. Pharmacokinetics were analyzed using nonlinear mixed-effects modeling. Four patients received one ePIPAC, three patients received two ePIPAC, and thirteen patients received ≥ 3 ePIPAC. The population pharmacokinetic models adequately described the pharmacokinetics of oxaliplatin after ePIPAC. The plasma ultrafiltrate Cmax of oxaliplatin reached 1.36-1.90 µg/mL after 30 min with an AUC0-24 h of 9.6-11.7 µg/mL * h. The plasma Cmax reached 2.67-3.28 µg/mL after 90 min with an AUC0-24 h of 49.0-59.5 µg/mL * h. The absorption rate constant (Ka) was 1.13/h. Urine concentrations of oxaliplatin rapidly decreased to less than 3.60 µg/mL in 90% of the samples at day 7. Systemic exposure to oxaliplatin after ePIPAC seemed comparable to that after systemic chemotherapy, as described in other literature. Since this is an indirect comparison, future research should focus on the direct comparison between the systemic exposure to oxaliplatin after ePIPAC and after systemic chemotherapy. NCT03246321, Pre-results; ISRCTN89947480, Pre-results; NTR6603, Pre-results; EudraCT: 2017-000927-29, Pre-results.


Contrasting effects on halothane hepatotoxicity in the phenobarbital-hypoxia and triiodothyronine model: mechanistic implications.
Factors affecting halothane (H) hepatotoxicity were investigated in two animal models: 1) the phenobarbital-hypoxia model, and 2) the triiodothyronine (T3) model; in the latter we previously have shown that centrilobular necrosis occurs in T3 pretreated rats anesthetized with 1% H, in 21% oxygen for 2 h. Feeding worsens the hepatotoxic effects of H in the T3 model. SGPT levels were higher (P less than 0.001) in T3 pretreated fed animals (641.0 +/- 182.1 U/1) than in T3 pretreated fasted animals (121.9 +/- 30.5 U/1), and histologic grading of hepatic necrosis was more extensive (P less than 0.05) in fed than fasted rats. In contrast, in the phenobarbital-hypoxia model of H hepatotoxicity fasting potentiates the lesion, the severity of histologic grading was worse (P less than 0.001) 24 h after H exposure in fasted than fed rats. Fluoride levels were elevated (P less than 0.001) over control values in the phenobarbital pretreated fasted rats anesthetized with H under hypoxic conditions (15.34 +/- 0.90 microM) but not in T3 pretreated fed rats anesthetized by H in 21% oxygen (2.37 +/- 0.15 microM), indicating that reductive metabolism may not be a prerequisite for toxicity in the T3 model. There was no significant difference in the effect of H and deuterated H on hepatotoxicity in the T3 model. SGPT levels in T3 treated female rats (62.4 +/- 5.1 U/1) were higher (P less than 0.001) than in control female rats (30.5 +/- 1.7 U/1) after H exposure but much less (P less than 0.01) than in male rats (641.0 +/- 182.1 U/1), demonstrating a gender difference for toxicity. These studies show fundamental differences between the two models: 1) hypoxia is required for the phenobarbital-hypoxia model but not for the T3 model; 2) hepatic necrosis correlates with reductive metabolism in the phenobarbital-hypoxia model but not in the T3 model; and 3) nutritional status has important but opposite effects.


Renal profile of chronic hepatitis C patients with sofosbuvir-based therapy.
The impact of SOF-based therapy on renal functions is quite controversial in clinical practice. Therefore, we aimed to evaluate the serial changes of renal indices during SOF-based therapy in CHC patients with normal kidney function or mild renal impairment. We retrospectively reviewed all CHC patients who received different SOF-based regimens from January 2015 until December 2017, and presented with a baseline eGFR ≥ 30 ml/min/1.73m2. Patients who didn't achieve SVR, with missing creatinine or eGFR data, and patients with eGFR less than 30 ml/min/1.73m2 at baseline were excluded. eGFR was calculated for each time of evaluation using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. A total of 1004 patients were finally included. The mean serum creatinine and eGFR levels varied between 0.84 mg/dl and 106.53 ml/min/1.73m2 for baseline and 0.87 mg/dl and 104.24 ml/min/1.73m2 for SVR12, respectively. The maximum increase of creatinine was 3.69 mg/dl and the maximum decrease of eGFR level was 83.30 ml/min/1.73m2 during treatment. Moreover, 74.4% of treated patients stayed in the same eGFR category, 14.3% progressed to a higher eGFR category, and 11.3% had an improvement eGFR category at EOT and continued to SVR12. Age > 65 years, baseline eGFR, and ribavirin-containing regimens were independent risk factors of eGFR decline during and after SOF-based treatment. SOF-based therapies seem to be safe in CHC patients with baseline normal or slightly impaired renal function.


Amotosalen and ultraviolet A light efficiently inactivate MERS-coronavirus in human platelet concentrates.
This study aimed to assess the efficacy of the INTERCEPT™ Blood System [amotosalen/ultraviolet A (UVA) light] to reduce the risk of Middle East respiratory syndrome-Coronavirus (MERS-CoV) transmission by human platelet concentrates. Since 2012, more than 2425 MERS-CoV human cases have been reported in 27 countries. The infection causes acute respiratory disease, which was responsible for 838 deaths in these countries, mainly in Saudi Arabia. Viral genomic RNA was detected in whole blood, serum and plasma of infected patients, raising concerns of the safety of blood supplies, especially in endemic areas. Four apheresis platelet units in 100% plasma were inoculated with a clinical MERS-CoV isolate. Spiked units were then treated with amotosalen/UVA to inactivate MERS-CoV. Infectious and genomic viral titres were quantified by plaque assay and quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR). Inactivated samples were successively passaged thrice on Vero E6 cells to exclude the presence of residual replication-competent viral particles in inactivated platelets. Complete inactivation of MERS-CoV in spiked platelet units was achieved by treatment with Amotosalen/UVA light with a mean log reduction of 4·48 ± 0·3. Passaging of the inactivated samples in Vero E6 showed no viral replication even after nine days of incubation and three passages. Viral genomic RNA titration in inactivated samples showed titres comparable to those in pre-treatment samples. Amotosalen and UVA light treatment of MERS-CoV-spiked platelet concentrates efficiently and completely inactivated MERS-CoV infectivity (>4 logs), suggesting that such treatment could minimise the risk of transfusion-related MERS-CoV transmission.


Using multi-technology to characterize transboundary Hg pollution in the largest presently active Hg deposit in China.
Active Hg mines are primary sources of Hg contamination in the environment of mining districts and surrounding areas. Alleviation of Hg pollution requires knowledge of pollution sources, migration, and transform pathways across various environmental media. Accordingly, the Xunyang Hg-Sb mine, the largest active Hg deposit in China, presently was selected as the study area. GIS, TIMA, EPMA, μ-XRF, TEM-EDS, and Hg stable isotopes were adopted to investigate the spatial distribution, mineralogical characteristics, in situ microanalysis, and pollution sources of Hg in the environment medium at the macro- and micro-levels. The total Hg concentration in samples showed a regional distribution, with higher levels in areas close to the mining operations. The in situ distribution of Hg in soil was mainly associated with the mineralogical phases of quartz, and Hg was also correlated with Sb and S. Hg was also found to be rich mainly in quartz minerals in the sediment and showed different distributions of Sb. Hg hotspots had S abundances and contained no Sb and O. The contributions from the anthropogenic sources to soil Hg were estimated to be 55.35%, among which 45.97% from unroasted Hg ore and 9.38% from tailing. Natural input of soil Hg due to pedogenic processes accounted for 44.65%. Hg in corn grain was mainly derived from the atmosphere. This study will provide a scientific basis for assessing the current environmental quality in this area and minimizing further impacts that affect the nearby environmental medium.


Adult status of mildly retarded past-pupils from special education. Part one: Employment.
Among the accepted criteria for evaluating post-school adjustment of retarded persons are variables relating to employment and financial independence. The present study examined the post-school adjustment of 382 past-pupils of special schools for mildly retarded children in Ireland. Data were collected from school records and through structured interviews. Previous studies in this area were extensively reviewed and current findings confirm previously identified trends. Approximately three-quarters were found to be employed at the time of the study and just over three-quarters of these were in open employment. Additional detail revealed that two-thirds of those in open employment earned wages regarded as sufficient for financial independence, and the main occupations listed showed two-thirds were in unskilled employment. One-third of the past-pupils suffered from physical disability additional to mental retardation and this finding, not previously documented, is worthy of note. This characteristic, together with age, sex and I. Q. were the variables found to be most relevant to employment outcomes.


LncRNA SLCO4A1-AS1 facilitates growth and metastasis of colorectal cancer through β-catenin-dependent Wnt pathway.
Emerging evidence has shown long noncoding RNAs (lncRNAs) exert important roles in colorectal cancer (CRC) tumorigenesis. However, most lncRNAs involved in this process remain undefined and the underlying molecular mechanisms mediated by lncRNAs are largely unknown. An unbiased screening was used to identify novel lncRNAs involved in CRC according to an online-available data dataset. In situ hybridization (ISH) and qRT-PCR was used to detect lncRNA expression patterns. CCK8, colony formation, fluorescence activated cell sorter (FACS), transwell, xenograft nude mouse model and western blot assays were used to analyze the functions of SLCO4A1-AS1. RNA-pulldown, western blot, RNA fluorescence in situ hybridization (RNA-FISH) and electrophoretic mobility shift assay (EMSA) assays were utilized to explore the molecular mechanism of SLCO4A1-AS1. LncRNA SLCO4A1-AS1 was significantly upregulated in CRC tissues and its overexpression was closely related with poor prognosis and tumor metastasis. By knocking down SLCO4A1-AS1, we found that SLCO4A1-AS1 promoted the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of CRC cells in vitro, as well as inhibited cell apoptosis. Moreover, SLCO4A1-AS1 dramatically delayed tumor propagation in vivo. Mechanistically, SLCO4A1-AS1 activates Wnt/β-catenin signaling. SLCO4A1-AS1 enhanced the stability of β-catenin by impairing the interaction of β-catenin with GSKβ and inhibiting its phosphorylation. Finally, restoration of β-catenin protein level rescued the proliferation, migration and invasion in SLCO4A1-AS1-depleted CRC cells. SLCO4A1-AS1 serves as an oncogenic role in CRC through activating Wnt/β-catenin signaling pathway. And SLCO4A1-AS1 might be a useful biomarker for CRC diagnosis and prognosis.


Assessing ecological literacy and its application based on linguistic ecology: a case study of Guiyang City, China.
To address the frequent emergence of ecological problems, ecology has intersected with various disciplines. From the perspective of linguistic ecology, ecological literacy is an important concept that combines the subjects of ecology and linguistics. It not only discusses ecological issues, but also establishes a linguistic framework. Here, we constructed a quantitative method of assessing ecological literacy from the perspective of linguistic ecology. Ecological literacy was divided into five parts: ecological knowledge literacy, ecological awareness literacy, ecological ethics literacy, ecological emotional literacy, and ecological behavioral literacy. Each of these was set with four quantitative indicators that were evaluated through eight questions. A case study was conducted to investigate the ecological literacy of the inhabitants of Guiyang City, one of China's top ten ecologically advanced cities. The results showed that the proposed assessment method was an effective way to evaluate the level of ecological literacy comprehensively. In the case analysis, the overall ecological literacy level of Guiyang inhabitants was relatively good, and the levels of the five specific dimensions of them in descending order were as follows: ecological ethics literacy, ecological emotional literacy, ecological awareness literacy, ecological knowledge literacy, and ecological behavioral literacy. The results of this study are conducive to the production of targeted ways to improve the level of ecological literacy for sustainable development.


Deep brain stimulation therapy for treatment-refractory Tourette's syndrome: A review.
Tourette's syndrome is a chronic neurobehavioral disorder that can demonstrate refractoriness to conservative treatments, or to invasive nonsurgical treatments such as botulinum toxin infiltration, or to psychobehavioral treatments. In these cases, the surgical option is often proposed, either with lesional interventions, or more recently with deep brain stimulation (DBS). This latter modality is currently preferred because of its reversibility and modularity. Some relevant issues, however, still persist in terms of appropriate indication to treatment, selection of target, and follow-up evaluation.


Effects of an NMDA-receptor antagonist MK-801 on an MMN-like response recorded in anesthetized rats.
In the human brain, auditory sensory memory has been extensively studied using a well-defined component of event-related potential named the mismatch negativity (MMN). The MMN is generated in the auditory and frontal cortices in response to deviant stimuli. In monkeys, cortical N-methyl-d-aspartate (NMDA) receptors have a central role in the generation of the MMN. MMN-like responses have also been recorded in other animals, including rats. The present study aimed at determining whether the MMN-like response in rats depends on an intact NMDA-receptor system. We recorded auditory evoked responses during an oddball paradigm epidurally in anesthetized rats that had received intraperitoneal injections of saline or an NMDA-receptor antagonist MK-801. An MMN-like response was recorded in the oddball paradigm in saline-treated rats. Further, this response was dose-dependently blocked by MK-801. These results suggest that the MMN-like response in rats depends on an intact NMDA-receptor system.


Paediatric nurses' burnout and perceived health: The moderating effect of the common work-shift.
This study aimed to: (1) explore the relationship between paediatric nurses' burnout, perceived health and common work-shift, (2) examine the moderating effect of the common work-shift on the relationship between paediatric nurses' burnout and perceived health, (3) compare burnout and perceived health between paediatric nurses working on day shifts and night/alternate shifts. A cross-sectional, correlational design was used in this study. A convenient sample of 225 paediatric nurses was selected from nine hospitals in Jordan. Participants were surveyed using a self-administered questionnaire. The perceived health correlated negatively with paediatric nurses' burnout and their common work-shift. Also, nurses' burnout and common work-shift were significantly correlated. The common work-shift moderated the relationship between paediatric nurses' burnout and their health. To control the impact of paediatric nurses' burnout on their health, the ratio of the night-to-day shifts should be observed and balanced.


The effect of Tribulus terrestris supplementation on inflammation, oxidative stress, and performance of recreational runners: study protocol for a randomized placebo-controlled trial.
High intensity and endurance exercises lead to exercise-induced oxidative stress (EIOS), exercise-induced muscle damage (EIMD), and inflammation, which are the influencing factors on muscle soreness, localized swelling, and sports performance decrease. Therefore, the purpose of this study is to determine the effectiveness of Tribulus terrestris (TT) as an herbal supplement with antioxidant and anti-inflammatory properties on the nutritional, oxidative, inflammatory, and anti-inflammatory status, as well as the sports performance of recreational runners. This study is a double-blind, randomized, placebo-controlled trial, which will be conducted among recreational runners of Tabriz stadiums, Iran. Thirty-four recreational runners will be selected, and participants will be assigned randomly to two groups: to receive 500 mg TT supplement or placebo capsules twice daily for 2 weeks. Both groups will do high-intensity interval training (HIIT) workouts during the study. Baseline and post-intervention body composition, muscle pain, and aerobic and anaerobic performance will be assessed. In addition, assessment of malondialdehyde (MDA), total antioxidant capacity (TAC), total oxidant status (TOS), superoxide dismutase (SOD), glutathione peroxidase (GPx), uric acid (UA), 8-iso-prostaglandin F2α (8-iso-PGF2α), protein carbonyl (PC), catalase (CAT), glutathione (GSH), nitric oxide (NO), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), creatine kinase (CK), myoglobin (MYO), lactate dehydrogenase (LDH), insulin-like growth factor-1 (IGF-1) irisin, cortisol, and brain-derived neurotrophic factor (BDNF) will be done during three blood samplings. Changes in oxidative stress, anti/inflammatory biomarkers, and sports performance will be assessed as primary outcomes. This study will be the first to assess the potential effects of TT on recreational runners. Our results will contribute to the growing body of knowledge regarding TT supplementation on the nutritional, oxidative, inflammatory, and anti-inflammatory status and sports performance in recreational runners. Iranian Registry of Clinical Trials ( www.irct.ir ) (ID: IRCT20150205020965N8 ). Registration date: 13 February 2021.


[FDG PET as an early nuclear medical diagnostic tool for aseptic wear-induced loosening of hip joint endoprostheses--a report of two cases].
To date, 2-[F-18]fluoro-2-deoxy-D-glucose PET (FDG PET) is used as a tool in oncology as well as myocardiological and cerebral functional diagnostics in the clinical routine. False positive results of tumor search imply new possibilities for use in diagnostics of inflammation. The two case reports presented here on aseptic loosening of endoprostheses caused by the rub of polyethylene with histological and immunohistological refurbishing call attention to the possible diagnostic valency of FDG PET as an early warning system regarding aseptic artificial limb loosening induced by the rub of polyethylene. By quantification of glucose metabolism with the "standard uptake value" (SUV) as well as specific storage samples from around the artificial limb, it is the aim of our study group in further examinations to develop an algorithm which permits to distinguish between septic and aseptic loosening.


Bovine hepatocyte growth factor and its receptor c-Met: cDNA cloning and expression analysis in the mammary gland.
Hepatocyte growth factor/scatter factor (HGF/SF) is a pleiotropic cytokine that plays a crucial role in the embryonic and postnatal development of various organs including the mammary gland. We cloned bovine HGF and its c-Met receptor cDNAs, and examined their expression during mammary gland development in dairy cows. The 2.5-kbp HGF cDNA clone contained a 2190 bp open reading frame coding a 730 amino acid protein, while the 4.8-kbp c-Met cDNA clone contained a 4152 bp open reading frame coding a 1384 amino acid protein. The bovine HGF and c-Met sequences exhibited more than 87% identity with those of other mammals. RT-PCR analysis revealed ubiquitous expression of both HGF and c-Met mRNAs in various bovine tissues tested. HGF mRNA was detected only in the inactive stage of bovine mammary gland development and not in the developing, lactating, and involuting stages, while c-Met mRNA was detected in the inactive and involuting stages. Immunohistochemical analysis demonstrated that the c-Met protein was found on mammary epithelial cells in the inactive, developing, and involuting stages, and on myoepithelial cells in all stages. These results suggest pivotal roles of HGF and c-Met in the development of bovine mammary gland.


Two genes encode the major membrane-associated protein of methanol-induced peroxisomes from Candida boidinii.
A massive proliferation of peroxisomes occurs in the yeast Candida boidinii when methanol is utilized as the sole carbon source; these peroxisomes contain the enzymes which catalyze the initial steps of methanol utilization. The most abundant peroxisomal membrane-associated protein has an apparent molecular mass of 20 kDa and is termed PMP20. We report the isolation of two genes that encode very similar forms of PMP20; this is the first report of genes that encode proteins associated with peroxisomal membranes. Southern analysis demonstrates that the two genes are on different loci, although there are several homologous regions of both 5'- and 3'-untranslated sequence. One of the areas of 5' homology is within the untranslated region of the mRNA. Within the coding region there are 35 base differences between the two genes that are reflected in only five amino acid differences. The mRNAs representing both genes of PMP20 are induced in cells grown in methanol-containing medium and are below detection in cells grown in glucose. S1 nuclease protection analysis indicates that there is a 2.5-fold difference in mRNA expression between the two genes when induced. The predicted sequences of both PMP20 genes show the absence of a cleaved amino-terminal leader sequence and the presence of only 1 cysteine residue. In agreement with previous biochemical data suggesting a peripheral association of this protein with the membrane (Goodman, J. M., Maher, J., Silver, P. A., Pacifico, A., and Sanders, D. (1986) J. Biol. Chem. 261, 3464-3468), there are no obvious membrane spanning regions predicted in the sequences. Both PMP20 gene products contain the carboxyl-terminal sequence AKL, similar to the putative SKL peroxisomal sorting sequence (Gould, S. J., Keller, G.-A., and Subramani, S. (1988) J. Cell Biol. 107, 897-905).


Clinical characteristics of KCNQ2 encephalopathy.
KCNQ2 mutations are associated with benign familial neonatal epilepsy (BFNE) or developmental and epileptic encephalopathy (DEE). In this study, we aimed to delineate the phenotype of KCNQ2 encephalopathy and evaluate the treatment response. Thirteen patients of KCNQ2 encephalopathy were included in the study. Characteristics of KCNQ2 mutations, electroclinical features, clinical course, and response to the treatment were analyzed. Age range of the thirteen patients was between 3 months and 20.9 years. The onset of seizures in 11 patients ranged from 1 to 3 days of age, while in the other two patients it was 7 and 40 days, respectively. Most common initial seizure types were tonic seizures. Initial EEGs were suppression burst pattern in seven patients and slow and disorganized background with multifocal epileptiform discharges in six patients. Initial epilepsy syndrome was Ohtahara syndrome in seven patients, neonatal focal seizure in five patients, and focal epilepsy beyond neonatal period in one patient. Sodium channel blockers including oxcarbazepine (OXC) (n = 3), lamotrigine (LTG) (n = 3), phenytoin (PHT) (n = 2), topiramate (TPM) (n = 2), and zonisamide (ZNS) (n = 1) were tried and found effective in eleven patients. Ultimately, 12 of 13 patients became seizure-free. However, developmental outcomes were poor. Sodium channel blockers are effective in seizure control in these patients with KCNQ2 encephalopathy. Early recognition of KCNQ2 encephalopathy and early use of sodium channel blockers might be helpful in seizure control.


Comparison of customized and cohort-based birthweight standards in identification of growth-restricted infants in GUSTO cohort study.
The aim was to evaluate the ability of customized and cohort birthweight standards in discriminating intrauterine growth retardation (IUGR). Birthweights (BWs) of GUSTO singleton infants born at gestational age (GA) 35-41 weeks were converted using two standards: (a) GUSTO cohort-based BW centile adjusted for GA and baby gender; (b) customized BW percentile calculator adjusted for maternal height and weight, race, parity, GA and gender. Infants were classified into three groups: (1) < 10th BW centile by customization- customized-SGA, (2) < 10th BW centile by GUSTO- GUSTO-SGA; and (3) > 10th BW centile by both standards - BOTH-non-SGA. Of the 1011 infant-mother dyads, 68 were customized-SGA and 104 were GUSTO-SGA, with concordance of 61% (n = 63) for SGA. While 5 (7%) of customized-SGA were not SGA by GUSTO-charts, 41 (39%) of GUSTO-SGA were not SGA by customized-charts. Customized-SGA had significantly the least growth in abdominal circumference (AC) and highest head circumference (HC): AC growth ratio between second and third trimester; and the lowest mean BW, ponderal index and placental weight than other groups. Customized-SGA standard was a better discriminator of pathologic fetal growth based on AC growth. It improved strength of association with pathology and in our population reduced false positives (41/104 = 39%) in the assessment of SGA.


Synthesis and trafficking of alkaloid biosynthetic enzymes.
The biosynthesis of plant natural products involves a large number of enzymes that create and elaborate a bewildering array of chemical structures, which are generally involved in ecophysiological interactions. Alkaloids are one of the largest groups of natural products and are generally produced through an assortment of intricate pathways. The application of molecular biochemical approaches to investigate the cell biology of alkaloid pathways has revealed a paradigm for the complex, yet highly ordered, organization of biosynthetic enzymes at both the cellular and subcellular levels. Many different cell types have been implicated in alkaloid formation and storage, in one case suggesting the intercellular transport of enzymes. The localization of enzymes to numerous cellular compartments shows the importance of protein targeting in the assembly of alkaloid pathways. Recent studies have also pointed to the possible interaction of biosynthetic enzymes in multi-enzyme complexes. These processes must be considered to be integral components of the mechanisms that regulate alkaloid biosynthesis and perhaps other natural product pathways.


Effects of the fruit essential oil of Cuminum cyminum L. on the acquisition and expression of morphine-induced conditioned place preference in mice.
Rewarding properties of opioids are now accepted and widely discussed. These properties can lead to long-term usage of these substances. The main purpose of this study was to investigate the effects of Cuminum cyminum fruit essential oil (FEO) on the acquisition and expression of morphine-induced conditioned place preference (CPP) in mice. CPP was induced by subcutaneous (s.c.) injection of morphine (5mg/kg) in 3 days conditioning schedule. Intraperitoneal (i.p.) administration of Cumin FEO (0.001%, 0.01%, 0.1%, 0.5%, 1% and 2%; 5 ml/kg) or Tween-80 (0.5%; 5 ml/kg) did not show any conditioning effects. Administration of Cumin FEO (0.001-2%; 5 ml/kg; i.p.), 60 min before test on day 5 (expression) decreased the conditioning scores at the doses of 1% and 2% while i.p. injection of Cumin FEO (0.001-2%; 5 ml/kg), 60 min before morphine injection (5mg/kg; s.c.) during 3 days of conditioning session (acquisition) significantly resulted in decrement of rewarding properties of morphine at the doses of 0.1%, 0.5%, 1% and 2% in dose-dependent manner. Tween-80 as a vehicle did not suppress the acquisition and expression of morphine-induced CPP. The results showed that the C. cyminum fruit essential oil reduces the acquisition and expression of morphine-induced conditioned place preference in mice.


Determination of trace element concentrations and stable lead, uranium and thorium isotope ratios by quadrupole-ICP-MS in NORM and NORM-polluted sample leachates.
This work focuses on the monitoring of the potential pollution in scenarios that involve NORM-related industrial activities (environmental or in-door scenarios). The objective was to develop a method to determine extent and origin of the contamination, suitable for monitoring (i.e. simple, fast and economical) and avoiding the use of too many different instruments. It is presented a radiochemical method that allows the determination of trace element concentrations and 206Pb/207Pb/208Pb, 238U/234U and 232Th/230Th isotope ratios using a single sample aliquot and a single instrument (ICP-QMS). Eichrom UTEVA® extraction chromatography minicolumns were used to separate uranium and thorium in sample leachates. Independent ICP-MS determinations of uranium and thorium isotope ratios were carried out afterwards. Previously a small aliquot of the leachate was used for the determination of trace element concentrations and lead isotope ratios. Several radiochemical arrangements were tested to get maximum performances and simplicity of the method. The performances of the method were studied in terms of chemical yields of uranium and thorium and removal of the potentially interfering elements. The established method was applied to samples from a chemical industry and sediments collected in a NORM-polluted scenario. The results obtained from our method allowed us to infer not only the extent, but also the sources of the contamination in the area.


The reproductive effects of beta interferon therapy in pregnancy: a longitudinal cohort.
To determine whether interferon therapy during human pregnancy increases reproductive risks in women. This longitudinal, controlled cohort study consisted of three groups of women: an exposed group, a disease matched unexposed group, and a healthy comparative group. Subjects were selected from women contacting the Motherisk Program regarding maternal beta interferon exposure, mostly for multiple sclerosis during pregnancy, from 1997 to 2004. After delivery all of the women were re-contacted for a follow-up interview regarding maternal health, pregnancy outcome, and neonatal health. The study group (n = 16 women, 23 pregnancies) were exposed to interferon beta-1a (Avonex, Rebif) and interferon-1b (Betaseron). There was a decrease in mean birth weight in the exposed group (3,189 +/- 416 g) as compared to healthy controls (3,783 +/- 412 g, p = 0.002). Women exposed to beta interferon had a higher rate of miscarriages and stillbirths (39.1%) vs healthy controls (5%) (p = 0.03), even after correction for potential confounders. There were two major malformations (abnormality in the X chromosome, Down's syndrome) among exposed fetuses. Beta interferon therapy in the first trimester of pregnancy appears to be associated with an increased risk for fetal loss and low birth weight.


B and T cell immune response to small nuclear ribonucleoprotein particles in lupus mice: autoreactive CD4(+) T cells recognize a T cell epitope located within the RNP80 motif of the 70K protein.
Systemic lupus erythematosus is characterized by the presence of high titers of autoantibodies reacting with various components of the U1 small nuclear ribonucleoprotein particle (snRNP). It has been suggested that these antibodies are produced by an antigen-driven mechanism under the dependence of antigen-specific T cells. To investigate the role of T cell help in this process, we sought, with 20 overlapping peptides, the Th epitopes on the U1-70K snRNP in unprimed H-2(k) MRL / lpr lupus mice and immunized CBA normal mice. The peptide 131 - 151 was recognized by both IgG autoantibodies and CD4(+) T cells from 7 - 9-week-old MRL / lpr mice. In this test, antigen-presenting cells (APC) from MRL / lpr mice were required; APC from naive CBA mice failed to stimulate CD4(+) cells from MRL / lpr mice. The potential role of MRL / lpr B cells as APC, the expression of MHC class II molecules at their surface and their activation state (expression of CD69, CD80 / B7-1 and CD86 / B7-2 molecules) were studied. Peptide 131 - 151 bound both I-A(k) and I-E(k) class II molecules and favored an IL-2-positive T cell response but not IFN-gamma, IL-6 and IL-10 secretion. Segment 131 - 151 is localized within the RNP80 motif and contains residues that are highly conserved in many nuclear, nucleolar and cytoplasmic RNA binding proteins.


Re-socializing pre-health education in the context of COVID: Pandemic prompts for bio-social approaches.
COVID-19 has underlined the critical importance of bringing biosocial and biopsychosocial approaches to pre-health education. Given the striking social inequalities that the pandemic has both exposed and exacerbated, we argue that bridging between the biomedical and social sciences with such approaches is now more appropriate and urgently needed than ever. We therefore call for the re-socialization of pre-health education by teaching to develop socio-structural competencies alongside physical and biological science knowledge. We suggest that community partnerships, which address local inequalities and their global interdependencies, should be encouraged as an essential element in all pre-health education. Educators should also support such partnerships as opportunities for students who come from more minoritized and impoverished social backgrounds to see their own social knowledge-including community-based knowledge of health-injustices revealed by the pandemic-as the basis of biopsychosocial expertise. By prioritizing this reconceptualization of pre-health education, we can empower future health workers to prepare more adequately for future health crises in ways that are socially aware and structurally transformative.


A data storage and retrieval system for clinical research.
A data storage and retrieval system is presented that can be used for clinical research studies. The system is designed in such a way that the programs are independent of the application. It can be used by non-computer experts via a simple query language. Since it is bulit up in a modular way extensions can be easily made. The system is implemented on a PDP 11/70 under FORTRAN.


Energetics and mechanics of nutritive sucking in the preterm and term neonate.
Energetics and mechanics of sucking in preterm and term neonates were determined by simultaneous records of intraoral pressure, flow, volume, and work of individual sucks. Nine term infants (mean postconceptional age: 38.6 +/- 0.7 SD weeks; mean postnatal age: 18.4 +/- 6.1 SD days) and nine preterm infants (mean postconceptional age: 35.2 +/- 0.7 SD weeks; mean postnatal age: 21.9 +/- 5.4 SD days) were studied under identical feeding conditions. Preterm infants generated significantly lower peak pressure (mean values of 48.5 cm H2O compared with 65.5 cm H2O in term infants; P less than 0.01), and the volume ingested per such was generally less than or equal to 0.5 mL. Term infants demonstrated a higher frequency of sucking, a well-defined suck-pause pattern, and a higher minute consumption of formula. Energy and caloric expenditure estimations revealed significantly lower work performed by preterm infants for isovolumic feeds (1190 g/cm/dL in preterm infants compared with 2030 g.cm/dL formula ingested in term infants; P less than 0.01). Furthermore, work performed by term infants was disproportionately higher for volumes greater than or equal to 0.5 mL ingested. This study indicates that preterm infants expend less energy than term infants to suck the same volume of feed and also describes an objective technique to evaluate nutritive sucking during growth and development.


Rapid and differential diagnosis of foot-and-mouth disease, swine vesicular disease, and vesicular stomatitis by a new multiplex RT-PCR assay.
A highly sensitive and specific one-step multiplex RT-PCR assay has been developed and standardised for the simultaneous and differential detection of the most important vesicular viruses affecting livestock: foot-and-mouth disease virus (FMDV), swine vesicular disease virus (SVDV), and vesicular stomatitis virus (VSV). The method uses three primer sets, each one specific for the corresponding virus, selected to detect of all serotypes of FMD and VS. The detection range was confirmed by examination of a collection of 31 isolates of the three target viruses. The specificity of the assay was also demonstrated by testing other related viruses, uninfected cell line cultures and healthy pig tissues. The testing of blood and serum samples from animals infected experimentally proved that the method can be useful for early diagnosis of the diseases, even before the first vesicular lesions are visualized in the infected pigs. An assessment of the performance of the multiplex RT-PCR was carried out using a panel of more than 100 samples from animals infected experimentally, showing the suitability of the method for a rapid (less than 6h), sensitive and specific differential diagnosis in clinical samples. Additionally, a uniplex RT-PCR for VSV, that amplifies the two viral serotypes, was also developed and tested as a rapid tool for the diagnosis of this vesicular disease.


Study of the relation between the posterior malleolus fracture and the development of osteoarthritis.
At least 10% of ankle fractures involve the posterior malleolus of the tibia, which has been related to poorer long-term prognosis. Our aim was to analyse the clinical and functional outcomes of ankle fractures involving the posterior edge, treated surgically without direct reduction of the third malleolus. We performed a retrospective study of 45 patients aged under 60, who we classified into three groups in terms of the percentage of joint involvement of the posterior fragment (<10%, 10%-25% and >25%) assessing the functional outcomes using the visual analogue pain scale (VAS), the AOFAS scale (American Orthopedic Foot and Ankle Society) of the ankle and hindfoot and the global health questionnaire SF-36; we also analysed the degree of osteoarthritis with weight-bearing radiography, at least one year following the injury. The mean VAS pain score of the sample was 1.1 (0-5) at rest and 3 (0-8) on exercise; 88.4±10.1 on the AOFAS scale, and 68.5±19.3 points on the SF-36. Up to 18% of the patients developed radiographically significant osteoarthritis in the short and medium term (between 12 and 73months, with a mean of 33months). Of the patients, 55.6% had involvement of between 19% and 25% of the joint surface. We found that a larger posterior fragment size related to a greater degree of early-onset osteoarthritis (P<.03) and poorer AOFAS scores (P<.01). Ankle fractures involving the posterior malleolus seem to contribute to the development of early-onset osteoarthritis with functional limitation in young adults.


Diagnostic performance of dynamic MR defecography in assessment of dyssynergic defecation.
To assess diagnostic performance of MR defecographic findings in diagnosis of dyssynergic defecation (DD). This retrospective study included 46 patients with chronic constipation who met the Rome IV criteria for diagnosis of present or absent DD and underwent MRI between Jan 2015 and June 2020. Patients were divided into DD group (n = 24) and non-DD group (n = 22). Nine parameters were analyzed by two radiologists: anorectal angle (ARA) and M line at rest, defecation, and change between 2 phases; anal canal width; prominent puborectalis muscle; abnormal evacuation. Receiver operating characteristic (ROC) curves were plotted to extract the optimal cut-offs and area under the curve (AUC). Multivariate analysis was performed. Seven findings showed statistically significant difference between DD and non-DD groups. M line at defecation had highest odds ratio, followed by ARA change, ARA at defecation, M line change, prominent puborectalis muscle, abnormal evacuation and anal canal width, respectively. ARA change and prominent puborectalis muscle had highest specificity (95.5% and 100%, respectively). The optimal cut-offs of ARA at defecation, ARA change, M line at defecation, M line change and anal canal width were 122°, 1.5°, 3.25 cm, 1.9 cm and 8.5 mm, respectively. Multivariate logistic regression revealed two significant findings in differentiating between DD and non-DD, including M line at defecation (OR 23.31, 95% CI 3.10-175.32) and ARA at defecation (OR 13.63, 95% CI 1.94-95.53) with sensitivity, specificity, PPV, NPV and AUC of 79.2%, 95.5%, 95%, 80.8% and 0.87(95% CI 0.78-0.97), respectively. MR defecography has high diagnostic performance in diagnosis of DD. Although M line and ARA at defecation are two significant findings on multivariate analysis, ARA change less than 1.5 degrees and prominent puborectalis muscle have good specificity in DD diagnosis.


New European Resuscitation Council guidelines for pediatric life support and their implications for pediatric anesthesia: An educational article.
In this educational article, we summarize the changes in the new European Resuscitation Council guidelines for Pediatric Life Support, emphasizing the most important aspects for the anesthesiologist. Among these are: the use of two-thumb-encircling technique for thorax compressions in infants, 10 ml/kg as the standard volume fluid bolus and ventilation after intubation at an age-dependent rate. Using a fictitious case, we present a point-by-point summary of the changes and briefly mention some of the evidence behind them, referring the reader to the full guidelines for further evidence. We also give a summary of the incidence, causes, challenges, treatment, and prognosis of pediatric cardiac arrest in the operating room.


Differential effects of intra-ventral tegmental area ghrelin and glucagon-like peptide-1 on the stimulatory action of D-amphetamine and cocaine-induced ethanol intake in male Sprague Dawley rats.
In order to further elucidate the role of mesolimbic peptides in the expression of ethanol reward, the present study investigated the effects of ghrelin and glucagon-like peptide-1 (GLP-1) on ethanol intake, in addition to ethanol intake stimulated by systemic d-amphetamine or cocaine treatment. While a number of studies suggest that ghrelin plays an important role in mesolimbic reward, emerging data now indicate that GLP-1 receptor mechanisms inhibit reward signaling, possibly by directly or indirectly inhibiting ghrelinergic activity within the mesolimbic system. In the present study all rats were initially habituated to a 6% ethanol solution. We then demonstrated that intraperitoneal injections of d-amphetamine and cocaine increased ethanol intake compared to the vehicle condition. In subsequent testing we examined the effects of ventral tegmental area (VTA) ghrelin or vehicle paired with a fixed dose of d-amphetamine or vehicle. In separate rats we then investigated the impact of the GLP-1 agonist exendin-4 (Ex-4), injected into the VTA, on ethanol intake alone, or when Ex-4 was co-administered with d-amphetamine or cocaine. Our results indicated that VTA ghrelin significantly increased ethanol intake, and most importantly, potentiated the effect of d-amphetamine and cocaine on ethanol consumption. Conversely, VTA Ex-4 inhibited ethanol intake and antagonized the stimulatory effect of d-amphetamine and cocaine on ethanol consumption. In a final study we further demonstrated that VTA Ex-4 treatment significantly inhibited the combined stimulatory effects of ghrelin paired with d-amphetamine or ghrelin paired with cocaine. Overall our findings are consistent with a critical role for both ghrelin and GLP-1 receptor mechanisms in mesolimbic ethanol reward circuitry. Moreover, our results further suggest that ghrelin and GLP-1 modulate the stimulatory effect of psychostimulants on ethanol intake.


Fluoro and pentafluorothio analogs of the antitumoral curcuminoid EF24 with superior antiangiogenic and vascular-disruptive effects.
A series of 14 analogs of the curcuminoid EF24, (3E,5E)-3,5-bis[(2-fluorophenyl)methylene]-4-piperidinone, bearing fluorine or pentafluorothio substituents, were prepared and tested for antiproliferative, vascular-disruptive, and antiangiogenic activity, as well as for their influence on other cancer-relevant targets. They proved antiproliferative against eight cancer cell lines with IC50 values in the low single-digit micromolar to triple-digit nanomolar range. Like EF24, the hexafluoro 3c and 3d and bis(pentafluorothio) 4f derivatives arrested HT-29 colon carcinoma cells in G2/M phase of the cell cycle, yet inhibited angiogenesis, e.g. in zebrafish larvae, to a much greater extent. The antimigratory effects in 518A2 melanoma cells of 3c, its regioisomer 3d, and of 4f, originate from an inhibition of NF-κB translocation. Moreover, 3c and 3d showed potential as vascular-disruptive agents in chorioallantoic/vitelline membrane (CA/VM) assays.


Evolution of nanomedicine formulations for targeted delivery and controlled release.
Nanotechnology research over the past several decades has been aimed primarily at improving the physicochemical properties of small molecules to produce druggable candidates as well as for tumor targeting of cytotoxic molecules. The recent focus on genomic medicine and the success of lipid nanoparticles for mRNA vaccines have provided additional impetus for the development of nanoparticle drug carriers for nucleic acid delivery, including siRNA, mRNA, DNA, and oligonucleotides, to create therapeutics that can modulate protein deregulation. Bioassays and characterizations, including trafficking assays, stability, and endosomal escape, are key to understanding the properties of these novel nanomedicine formats. We review historical nanomedicine platforms, characterization methodologies, challenges to their clinical translation, and key quality attributes for commercial translation with a view to their developability into a genomic medicine. New nanoparticle systems for immune targeting, as well as in vivo gene editing and in situ CAR therapy, are also highlighted as emerging areas.


Geomorphological effects of animals in mountain streams: Impact and role.
Elucidating the impact of faunal activity on stream channels is an emerging field wherein ecologists, fluvial geomorphologists, and engineers collaborate to research and manage fluvial ecosystems. Here, we focused on the geomorphological effects of animals in mountain streams. This ecosystem merits conservation measures as it furnishes cold-water refugia. We searched literature addressing the impact of various animal taxa on the river/stream bed structure. The citation sources were the Web of Science, Scopus, and ScienceDirect databases covering 1975-early 2020. We examined all animal taxa with documented or potential zoogeomorphological effects upon streams and assigned spatiotemporal scales to their impacts. Interpreting the literature was challenging due to a lack of uniformity in data treatment between species groups and over time. Though human interactions prevail in stream channels, animals also have a substantial effect on a spatial scale and their modifications are more durable. In general, animals markedly influence aquatic habitats. This literature compilation revealed much information about the geomorphological effects of beavers, redd-building fish, and large bottom-dwelling fish. The scale of impact of invertebrates such as crayfish or case-building caddisfly larvae on stony-gravel bottoms has previously been demonstrated. However, previous research has concentrated on only one taxon and has not demonstrated the bioaccumulation effect of multiple taxa. Quantitative data have been presented only for large terrestrial mammals crossing streams. There was comparatively little information on the impact of other terrestrial taxa on stream geomorphology. There were also few or no quantitative data on the impacts of aquatic fauna on mountain stream channels. Much has been reported about the effects of burying invertebrates but relatively little is known about the impacts of burying fish such as lamprey larvae. The present review highlights numerous outstanding information gaps. It is hoped that this review will facilitate ongoing zoogeomorphological research.


PLA2G4A mutants modified protective effect of tea consumption against colorectal cancer.
The primary aim was to respectively evaluate PLA2G4A mutants modifying protective effect of tea consumption against colorectal cancer (CRC), colon and rectal cancer. All participants were recruited from January 2006 to April 2008. The information about tea consumption was collected by a structured questionnaire. CRC patients were diagnosed based on histology. Four single-nuclear polymorphisms (SNPs) in PLA2G4A gene were selected. Multiple logistic regression models were used for assessing the joint effects between tea consumption and SNPs on CRC, colon and rectal cancer. Three hundred patients with CRC and 296 controls well-matched were used in the final analyses. The significant individual associations between four SNPs (rs6666834, rs10911933, rs4650708 and rs7526089) and CRC were not observed. However, their CTAC haplotype was significantly associated with the increased risk of CRC (OR = 3.06; 95%CI = 1.52-6.19), compared with TCAC haplotype. Drinking tea was correlated with a decreased risk of CRC after adjustment for covariates (OR = 0.61; 95%CI = 0.39-0.97). Meanwhile, compared with no-tea drinkers with TT/CT genotype of rs6666834, tea drinkers with TT/CT or CC had significant lower risk of CRC (OR = 0.6, 95%CI = 0.36-1.00 for TT/CT; 0.38, 0.19-0.74 for CC). The joint effects between the remaining three SNPs and drinking tea on CRC were observed as well. Similar findings were observed on colon and rectal cancers. Tea consumption and haplotype of mutants in PLA2G4A gene were respectively associated with the risk of CRC. PLA2G4A mutants modified the protective effect of tea consumption against CRC, colon and rectal cancers in Chinese population.


Quantitative histological studies on the lateral geniculate nucleus in the cat. IV. Numerical aspects of the transfer from restinal fibers to cortical relay.
The numerical data, gained both from the quantitative histology and Golgi stained material was completed with those of optic fibers. The number of X and Y fibers was estimated on the basis of our results, on the data of literature and from the ratio of the large and medium size relay neurons. The crossed and uncrossed fibers were counted and compared with the number of relay neurons in layer A and A1. Knowing the different numerical and metrical counts of neuronal elements in LGN of cat some calculations were carried out on the overlaping of optic fiber arborizations, on the intersections of dendritic ramification points of relay neurons and on the spatial arrangement of both the optic terminals and the relay neurons. The comparison of the neumerical data on relay neurons and optic fibers and their relations were the basic factors of considerations on divergence and convergence of retinal input.