Sequential or parallel decomposed processing of two-digit numbers? Evidence from eye-tracking.
While reaction time data have shown that decomposed processing of two-digit numbers occurs, there is little evidence about how decomposed processing functions. Poltrock and Schwartz (1984) argued that multi-digit numbers are compared in a sequential digit-by-digit fashion starting at the leftmost digit pair. In contrast, Nuerk and Willmes (2005) favoured parallel processing of the digits constituting a number. These models (i.e., sequential decomposition, parallel decomposition) make different predictions regarding the fixation pattern in a two-digit number magnitude comparison task and can therefore be differentiated by eye fixation data. We tested these models by evaluating participants' eye fixation behaviour while selecting the larger of two numbers. The stimulus set consisted of within-decade comparisons (e.g., 53_57) and between-decade comparisons (e.g., 42_57). The between-decade comparisons were further divided into compatible and incompatible trials (cf. Nuerk, Weger, & Willmes, 2001) and trials with different decade and unit distances. The observed fixation pattern implies that the comparison of two-digit numbers is not executed by sequentially comparing decade and unit digits as proposed by Poltrock and Schwartz (1984) but rather in a decomposed but parallel fashion. Moreover, the present fixation data provide first evidence that digit processing in multi-digit numbers is not a pure bottom-up effect, but is also influenced by top-down factors. Finally, implications for multi-digit number processing beyond the range of two-digit numbers are discussed.


Uncontrolled-rate freezing of peripheral blood progenitor cells allows successful engraftment by sparing primitive and committed hematopoietic progenitors.
Uncontrolled-rate freezing (URF) techniques, which are fast and easy, could represent an attractive alternative to controlled-rate cryopreservation procedures which are time consuming and require high-level technical abilities. It was the aim of the present study to evaluate, on a routine basis, whether URF might spare primitive hematopoietic progenitors and maintain engrafting capacity. One-hundred and nineteen peripheral blood progenitor cells (PBPC) collections from 104 patients with hematologic malignancies were cryopreserved in bags, with an URF procedure, in a cryoprotectant solution consisting of PBS, HSA and 10% DMSO and stored in liquid nitrogen. PBPC bags were tested before cryopreservation and at thawing for primitive (LTC-IC) and committed hematopoietic progenitors (CFU-Mix, BFU-E, CFU-GM) by means of long- and short-term culture assays, respectively. In addition, PBPC bags were evaluated for CD34+ cell numbers. Although thawing was associated with a statistically significant reduction of the absolute number of nucleated cells, recovery of LTC-IC, CFU-Mix, BFU-E, CFU-GM and CD34+ cells was not affected by the freezing/thawing procedures. No adverse effects were reported at thawing and only mild transient reactions were recorded in 22 patients during reinfusion of cryopreserved PBPC. All the patients underwent myeloablative therapy followed by reinfusion of PBPC, and prompt and rapid hematopoietic recovery was obtained in all patients. Our freezing procedure is fast and easy, and allows rapid hematopoietic recovery after myeloablative therapy by sparing primitive and committed hematopoietic progenitors. Our study strongly supports technical improvements aimed at cost reduction and feasibility of routine freezing procedures.


Directing Crystallization Outcomes of Conformationally Flexible Molecules: Polymorphs, Solvates, and Desolvation Pathways of Fluconazole.
Control over polymorphism and solvatomorphism in API assisted by structural information, e.g., molecular conformation or associations via hydrogen bonds, is crucial for the industrial development of new drugs, as the crystallization products differ in solubility, dissolution profile, compressibility, or melting temperature. The stability of the final formulation and technological factors of the pharmaceutical powders further emphasize the importance of precise crystallization protocols. This is particularly important when working with highly flexible molecules with considerable conformational freedom and a large number of hydrogen bond donors or acceptors (e.g., fluconazole, FLU). Here, cooling and suspension crystallization were applied to access polymorphs and solvates of FLU, a widely used azole antifungal agent with high molecular flexibility and several reported polymorphs. Each of four polymorphic forms, FLU I, II, III, or IV, can be obtained from the same set of alcohols (MeOH, EtOH, isPrOH) and DMF via careful control of the crystallization conditions. For the first time, two types of isostructural channel solvates of FLU were obtained (nine new structures). Type I solvates were prepared by cooling crystallization in Tol, ACN, DMSO, BuOH, and BuON. Type II solvates formed in DCM, ACN, nPrOH, and BuOH during suspension experiments. We propose desolvation pathways for both types of solvates based on the structural analysis of the newly obtained solvates and their desolvation products. Type I solvates desolvate to FLU form I by hydrogen-bonded chain rearrangements. Type II solvates desolvation leads first to an isomorphic desolvate, followed by a phase transition to FLU form II through hydrogen-bonded dimer rearrangement. Combining solvent-mediated phase transformations with structural analysis and solid-state NMR, supported by periodic electronic structure calculations, allowed us to elucidate the interrelations and transformation pathways of FLU.


INHIBITION OF ANTIBODY SYNTHESIS BY L-PHENYLALANINE.
Antibody synthesis in response to the injection of diphtheria toxoid into rabbits and rats was used to study the effects of an excess of the amino acid L-phenylalanine on protein synthesis. Injections of phenylalanine produced a marked inhibition of antibody synthesis in both the rat and the rabbit. The dosage of phenylalanine used caused an increase over the normal concentration of phenylalanine in the plasma and spleen of rats, but did not cause a loss of weight or serum protein changes in the treated animals.


Factorial and Economic Evaluation of an Aqueous Two-Phase Partitioning Pilot Plant for Invertase Recovery From Spent Brewery Yeast.
Aqueous two-phase systems (ATPS) have been reported as an attractive biocompatible extraction system for recovery and purification of biological products. In this work, the implementation, characterization, and optimization (operational and economic) of invertase extraction from spent brewery yeast in a semi-automatized pilot plant using ATPS is reported. Gentian violet was used as tracer for the selection of phase composition through phase entrainment minimization. Yeast suspension was chosen as a complex cell matrix model for the recovery of the industrial relevant enzyme invertase. Flow rates of phases did not have an effect, given that a bottom continuous phase is given, while load of sample and number of agitators improved the recovery of the enzyme. The best combination of factors reached a recovery of 129.35 ± 2.76% and a purification factor of 4.98 ± 1.10 in the bottom phase of a PEG-Phosphate system, also resulting in the removal of inhibitor molecules increasing invertase activity as reported by several other authors. Then, an economic analysis was performed to study the production cost of invertase analyzing only the significant parameters for production. Results indicate that the parameters being analyzed only affect the production cost per enzymatic unit, while variations in the cost per batch are not significant. Moreover, only the sample load is significant, which, combined with operational optimization results, gives the same optimal result for operation, maximizing recovery yield (15% of sample load and 1 static mixer). Overall res ults of these case studies show continuous pilot-scale ATPS as a viable and reproducible extraction/purification system for high added-value biological compounds.


Data-Driven Two-Stage Framework for Identification and Characterization of Different Antibiotic-Resistant Escherichia coli Isolates Based on Mass Spectrometry Data.
In clinical microbiology, matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) is frequently employed for rapid microbial identification. However, rapid identification of antimicrobial resistance (AMR) in Escherichia coli based on a large amount of MALDI-TOF MS data has not yet been reported. This may be because building a prediction model to cover all E. coli isolates would be challenging given the high diversity of the E. coli population. This study aimed to develop a MALDI-TOF MS-based, data-driven, two-stage framework for characterizing different AMRs in E. coli. Specifically, amoxicillin (AMC), ceftazidime (CAZ), ciprofloxacin (CIP), ceftriaxone (CRO), and cefuroxime (CXM) were used. In the first stage, we split the data into two groups based on informative peaks according to the importance of the random forest. In the second stage, prediction models were constructed using four different machine learning algorithms-logistic regression, support vector machine, random forest, and extreme gradient boosting (XGBoost). The findings demonstrate that XGBoost outperformed the other four machine learning models. The values of the area under the receiver operating characteristic curve were 0.62, 0.72, 0.87, 0.72, and 0.72 for AMC, CAZ, CIP, CRO, and CXM, respectively. This implies that a data-driven, two-stage framework could improve accuracy by approximately 2.8%. As a result, we developed AMR prediction models for E. coli using a data-driven two-stage framework, which is promising for assisting physicians in making decisions. Further, the analysis of informative peaks in future studies could potentially reveal new insights. IMPORTANCE Based on a large amount of matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) clinical data, comprising 37,918 Escherichia coli isolates, a data-driven two-stage framework was established to evaluate the antimicrobial resistance of E. coli. Five antibiotics, including amoxicillin (AMC), ceftazidime (CAZ), ciprofloxacin (CIP), ceftriaxone (CRO), and cefuroxime (CXM), were considered for the two-stage model training, and the values of the area under the receiver operating characteristic curve (AUC) were 0.62 for AMC, 0.72 for CAZ, 0.87 for CIP, 0.72 for CRO, and 0.72 for CXM. Further investigations revealed that the informative peak m/z 9714 appeared with some important peaks at m/z 6809, m/z 7650, m/z 10534, and m/z 11783 for CIP and at m/z 6809, m/z 10475, and m/z 8447 for CAZ, CRO, and CXM. This framework has the potential to improve the accuracy by approximately 2.8%, indicating a promising potential for further research.


Practical approaches to improving translatability and reproducibility in preclinical pain research.
Pain research continues to face the challenge of poor translatability of pre-clinical studies. In this short primer, we are summarizing the possible causes, with an emphasis on practical and constructive solutions. In particular, we stress the importance of increased heterogeneity in animal studies; formal or informal pre-registration to combat publication bias; and increased statistical training in order to help pre-clinical scientists appreciate the usefulness of available experimental design and reporting guidelines.


Mechanism-based inhibition of GH127/146 cysteine glycosidases by stereospecifically functionalized l-arabinofuranosides.
To understand the precise mechanism of the glycoside hydrolase (GH) family 127, a cysteine β-l-arabinofuranosidase (Arafase) - HypBA1 - has been isolated from Bifidobacterium longum in the human Gut microbiota, and the design and synthesis of the mechanism-based inhibitors such as l-Araf-haloacetamides have been carried out. The α-l-Araf-azide derivative was used as the monoglycosylamine equivalent to afford the l-Araf-chloroacetamides (α/β-1-Cl) as well as bromoacetamides (α/β-1-Br) in highly stereoselective manner through Staudinger reaction followed by amide formation with/without anomerization. Against HypBA1, the probes 1, especially in the case of α/β-1-Br inhibited the hydrolysis. Conformational implications of these observations are discussed in this manuscript. Additional examinations using l-Araf-azides (α/β-5) resulted in further mechanistic observations of the GH127/146 cysteine glycosidases, including the hydrolysis of β-5 as the substrate and oxidative inhibition by α-5 using the GH127 homologue.


[Epidemiology of the avoidable delay in patients with acute myocardial infarct admitted to the coronary care unit].
Despite the availability of safe and effective drugs for the treatment of acute myocardial infarction, nowadays, only a minority of patients arrive at the hospital early enough to receive the benefit of these treatments. The reason for this is still uncertain. Our intention was to review the literature on this topic, check if there were some issues that could be identified as delay-promoters, and see if any Italian data were available, in order to make a comparison with international data. We found a substantial agreement among the Authors that median total delay (i.e. the time between the onset of symptoms and the arrival at the hospital) is between three and five hours, and it seems that this has remained fairly stable over the years. The decision delay (i.e. the time between the onset of symptoms and the first medical contact) is almost unanimously indicated as the major single component in the total delay. This represents around 40% of the pre-hospital phase. Transportation time appears to play only a slight role, if indeed any, in the total delay. Nonetheless, mobile coronary units have consistently shown that they can reduce thrombolysis time (e.g. the time between the onset of symptoms and the start of thrombolytic infusion) by almost 60 minutes, and this time-gain is comparable with the reduction in total delay obtained in Sweden with a media campaign. Strongly contrasting results were obtained from the analysis of the delay-determining factors.(ABSTRACT TRUNCATED AT 250 WORDS)


Mammary and submandibular gland epidermal growth factor expression is reduced by calorie restriction.
Calorie restriction reduces mammary mitogenesis and tumorigenesis. To test whether epidermal growth factor (EGF) levels are influenced by calorie intake, 72 four-week-old C3H/HeOu mice were separated into two groups and either fed ad libitum (group AL) or calorie-restricted at a mean 19% (group CR). Three mice from each group were evaluated when 6, 8, 10, and 12 weeks old for submandibular gland transcription of EGF and beta-actin RNA for levels of EGF protein in the submandibular gland, mammary gland, and serum and for immunohistological evidence of EGF protein within the submandibular and mammary glands. Submandibular levels of EGF RNA and protein and mammary and serum levels of EGF protein were similar between dietary groups when mice were 6 and 8 weeks old. Mean EGF:beta-actin RNA transcription in submandibular glands of 12-week-old mice were approximately 10-fold greater in AL compared to CR mice (ratio means, 1.499 versus 0.157, respectively; P < 0.01). Mean submandibular levels of EGF protein were greater in 10-week-old AL compared to CR mice (7017.4 versus 4098.5 ng/mg protein, respectively; P < 0.05) and even greater in 12-week-old AL compared to CR mice (4342.6 versus 137.9 ng/mg protein; P < 0.001). Mean mammary levels of EGF protein were greater among 12-week-old AL compared to CR mice (7.8 versus 5.0 ng/mg protein; P < 0.05). Serum levels of EGF did not differ between dietary cohorts. More anti-EGF immunoprecipitate was present in submandibular and mammary gland sections of 10- and 12-week-old AL compared to CR mice. Lowered EGF levels may contribute to the antiproliferative and antineoplastic effects of calorie restriction.


The burden and utility of routine follow-up at one year after primary arthroplasty.
Routine surveillance of primary hip and knee arthroplasties has traditionally been performed with office follow-up visits at one year postoperatively. The value of these visits is unclear. The present study aims to determine the utility and burden of routine clinical follow-up at one year after primary arthroplasty to patients and providers. All patients (473) who underwent primary total hip (280), hip resurfacing (eight), total knee (179), and unicompartmental knee arthroplasty (six) over a nine-month period at a single institution were identified from an institutional registry. Patients were prompted to attend their routine one-year postoperative visit by a single telephone reminder. Patients and surgeons were given questionnaires at the one-year postoperative visit, defined as a clinical encounter occurring at nine to 15 months from the date of surgery, regarding value of the visit. Compliance with routine follow-up at one year was 35%. The response rate was over 80% for all questions in the patient and clinician surveys. Overall, 75% of the visits were for routine surveillance. Patients reported high satisfaction with their visits despite the general time for attendance, including travel, being over four hours. Surgeons found the visits more worthwhile when issues were identified or problems were addressed. Patient compliance with follow-up at one year postoperatively after primary hip and knee is low. Routine visits of asymptomatic patients deliver little practical value and represent a large time and cost burden for patients and surgeons. Remote strategies should be considered for routine postoperative surveillance primary hip and knee arthroplasties beyond the acute postoperative period. Cite this article: Bone Joint J 2020;102-B(7 Supple B):85-89.


Prognostic value of olfactory bulb volume measurement for recovery in postinfectious and posttraumatic olfactory loss.
Several prognostic factors influencing the recovery from olfactory dysfunction have been described. The aim of this study was to investigate whether olfactory bulb volume could be used as a new predictor of olfactory recovery in postinfectious and posttraumatic olfactory loss. Cohort study; Level of evidence, 4. Setting Tertiary university clinic, department of otolaryngology. A cohort of 60 patients with postinfectious (n = 28) and posttraumatic olfactory loss (n = 32) was investigated. Assessment of olfactory function was performed using orthonasal (Sniffin' Sticks test) and retronasal psychophysical olfactory tests, at the time of the diagnosis (t1) and 15 months later (t2). All patients were examined on 3 tesla magnetic resonance imaging, and the olfactory bulbs volume was assessed using planimetric contouring at the time of the diagnosis (t1). Recovery rate was 25% in patients with posttraumatic olfactory loss and 36% in patients with postinfectious olfactory loss. There was a correlation between both orthonasal and retronasal olfactory testing and the initial measurement of the total olfactory bulb volume. In addition, we observed a significant correlation between changes in olfactory functions and initial measurement of the total olfactory bulb volume, with larger volumes relating to higher improvement of olfactory function. Finally, we found that none of the patients with a total olfactory bulb volume of 40 mm(3) or less exhibited recovery of olfactory function. Olfactory bulb volume seems to be a predictor of olfactory recovery in patients with postinfectious and posttraumatic olfactory loss.


Relationships between Canadian adult cancer survivors' annual household income and emotional/practical concerns, help-seeking and unmet needs.
The objective of this study was to explore the relationship among income and emotional/practical concerns, help-seeking and unmet needs for cancer survivors aged 18 to 64 years one to three years after treatment. A cross-sectional survey was mailed in 2016 to 40,790 survivors randomly selected from 10 Canadian provincial cancer registries. Thirty-three percent responded. A trend analysis was conducted for survivors most likely to be in the workforce exploring the relationship across four income levels and emotional/practical concerns, whether help was sought for identified concerns, and whether help was received. A total of 4,264 respondents, aged 18-64, provided useable data with breast (34.4%) and colo-rectal (15.0%) accounting for the primary cancer type and 32.0% reporting annual household incomes of <$50,000. More than 94% of respondents indicated having emotional or practical concerns. Between one-third and one-half of the respondents sought help for their concerns and, of those, between one-third and one-half experienced difficulty finding help or did not obtain assistance. Significant trends across income categories indicated greater percentages of those in lower income categories experienced emotional and practical concerns, rated their concerns as 'big', sought help, and had difficulty finding help to address their concerns. Clearly adult cancer survivors experience emotional and practical concerns. Healthcare professionals have important roles monitoring these concerns and connecting those who desire help to relevant services. Opportunities should be given to individuals, regardless of income level, to indicate if they have concerns and if they would like assistance.


Identification of Stage-Specific Gene Expression Signatures in Response to Retinoic Acid during the Neural Differentiation of Mouse Embryonic Stem Cells.
We have previously established a protocol for the neural differentiation of mouse embryonic stem cells (mESCs) as an efficient tool to evaluate the neurodevelopmental toxicity of environmental chemicals. Here, we described a multivariate bioinformatic approach to identify the stage-specific gene sets associated with neural differentiation of mESCs. We exposed mESCs (B6G-2 cells) to 10(-8) or 10(-7) M of retinoic acid (RA) for 4 days during embryoid body formation and then performed morphological analysis on day of differentiation (DoD) 8 and 36, or genomic microarray analysis on DoD 0, 2, 8, and 36. Three gene sets, namely a literature-based gene set (set 1), an analysis-based gene set (set 2) using self-organizing map and principal component analysis, and an enrichment gene set (set 3), were selected by the combined use of knowledge from literatures and gene information selected from the microarray data. A gene network analysis for each gene set was then performed using Bayesian statistics to identify stage-specific gene expression signatures in response to RA during mESC neural differentiation. Our results showed that RA significantly increased the size of neurosphere, neuronal cells, and glial cells on DoD 36. In addition, the gene network analysis showed that glial fibrillary acidic protein, a neural marker, remarkably up-regulates the other genes in gene set 1 and 3, and Gbx2, a neural development marker, significantly up-regulates the other genes in gene set 2 on DoD 36 in the presence of RA. These findings suggest that our protocol for identification of developmental stage-specific gene expression and interaction is a useful method for the screening of environmental chemical toxicity during neurodevelopmental periods.


The antiviral compound HPA-23 can prevent scrapie when administered at the time of infection.
The effects of up to 12 daily doses of HPA-23 (ammonium 5-tungsto-2-antimoniate) on scrapie were studied using five experimental models of the disease, some with widely different incubation times. Treatment of animals with HPA-23, starting just before injecting scrapie, produced survivors. In some experiments, animals were fully protected against several hundred infectious units of scrapie. Treatment of animals after infection was far less effective. Prolonging the treatment for several weeks was no more effective than treating for a few days. In a very long incubation model of scrapie, the course of 12 daily doses of HPA-23 represented less than 3 per cent of the total incubation period. HPA-23 may interact with certain cells of the lymphoreticular system, preventing infection and, perhaps, the early replication of agent.


Dentate spikes and learning: disrupting hippocampal function during memory consolidation can improve pattern separation.
Hippocampal dentate spikes (DSs) are short-duration, large-amplitude fluctuations in hilar local field potentials and take place while resting and sleeping. During DSs, dentate gyrus granule cells increase firing while CA1 pyramidal cells decrease firing. Recent findings suggest DSs play a significant role in memory consolidation after training on a hippocampus-dependent, nonspatial associative learning task. Here, we aimed to find out whether DSs are important in other types of hippocampus-dependent learning tasks as well. To this end, we trained adult male Sprague-Dawley rats in a spatial reference memory task, a fixed interval task, and a pattern separation task. During a rest period immediately after each training session, we either let neural activity to take place as usual, timed electrical stimulation of the ventral hippocampal commissure (vHC) to immediately follow DSs, or applied the vHC stimulation during a random neural state. We found no effect of vHC stimulation on performance in the spatial reference memory task or in the fixed interval task. Surprisingly, vHC stimulation, especially contingent on DSs, improved performance in the pattern separation task. In conclusion, the behavioral relevance of hippocampal processing and DSs seems to depend on the task at hand. It could be that in an intact brain, offline memory consolidation by default involves associating neural representations of temporally separate but related events. In some cases this might be beneficial for adaptive behavior in the future (associative learning), while in other cases it might not (pattern separation). NEW & NOTEWORTHY The behavioral relevance of dentate spikes seems to depend on the learning task at hand. We suggest that dentate spikes are related to associating neural representations of temporally separate but related events within the dentate gyrus. In some cases this might be beneficial for adaptive behavior in the future (associative learning), while in other cases it might not (pattern separation).


Maize plastid photogenes: mapping and photoregulation of transcript levels during light-induced development.
Positively photoregulated regions that show increased transcript levels upon illumination of dark-grown seedlings are scattered over approximately 19% of the maize plastid chromosome. Some photogenes, i.e., genes within these regions, are transcribed individually, whereas others that are transcribed as polycistronic mRNAs appear to be functionally organized into operons. Multiple light-induced transcripts are complementary to most photogenes; these mRNAs are not present in equimolar amounts during plastid photomorphogenesis, but particular transcripts predominate at specific stages of development. Most, but not all, photogene RNA pools reach a maximum size (after either 10, 20, or 44 h of illumination) and then fall to approximately preillumination levels. These data and other considerations argue that photogene expression control is fundamentally transcriptional and that there is more than one expression class. Transcripts of the maize plastid gene for the large subunit of ribulose bisphosphate carboxylase reach a maximum by 20 h of illumination; transcripts of the nuclear gene for the small subunit of this enzyme continue to accumulate and fall considerably later. These data suggest that the level of transcription of the latter gene in the nucleus may be regulated by events in the chloroplast.


[Pneumoencephalography in the first year from the onset of epileptic seizures].
Pneumoencephalography was performed in 88 patients within the first year since their first epileptic seizure (of these, 53 were studied during the first 6 months). The control group comprised 31 patients with 12 to 30 months history of the seizures. Pronounced changes in the subarachnoidal space in 30 patients were found to be related to clinical signs and the disease history more closely than did the ventricular system pathology. The latter was generally considered to be a result of past ailments, not reflecting the course of the early stages of epileptic process. The pronounced subarachnoidal pathology proved to be an unfavorable prognostic sign. More close relation of the establishing epileptic process with the subarachnoidal changes could possibly confirm the cortical localization of the primary epileptic foci.


Reconstituted basement membrane influences prolactin, LH, and FSH secretion from adult and fetal adenohypophyseal cells in vitro.
These investigations tested the hypothesis that secretion of prolactin (PRL), LH, and FSH in vitro is influenced by the substratum on which adult or fetal adenohypophyseal cells are cultured. Adenohypophyses were removed from adult male Golden Syrian hamsters and from fetal hamsters on day 16 of gestation. The glands were dissociated and cultured in a 1:1 mixture of Dulbecco's Modified Eagle's Medium (DMEM) and Ham's F-12 medium containing 10% fetal bovine serum (FBS), 25 mM Hepes, and antibiotics. The cells were cultured on three substrata: glass, laminin, and the reconstituted basement membrane of the Engelbreth-Holm-Swarm (EHS) tumor (Matrigel). Medium was collected and replaced every 48 h for 14-22 days. Concentrations of PRL, LH, and FSH in medium were measured by RIA. The substratum influenced hormone secretion. PRL concentrations were elevated in cultures of adult cells on Matrigel in each of four experiments. Adenohypophyseal cells on Matrigel maintained a rounded shape longer than cells on glass or laminin. In studies using fetal adenohypophyseal cells, PRL concentrations were elevated significantly in medium from cultures on Matrigel at and after 2 days as were concentrations of LH and FSH after 6 days. Additional experiments showed that the higher PRL concentrations in medium surrounding adult cells plated on Matrigel were not due to the release of soluble factors from Matrigel, differential cell attachment on Matrigel, the differential presence of adenohypophyseal fibroblasts, nor differential rates of cell proliferation. The results show that Matrigel maintains the secretion of PRL from adult adenohypophyseal cells in vitro more effectively than glass or laminin substrata and support the hypothesis that cell-matrix interactions mediate the observed differences. The results also show that in long-term cultures (14-22 days), fetal adenohypophyseal cells secrete significantly more PRL, LH, and FSH on Matrigel than they secrete when cultured on glass or laminin. Thus, Matrigel influences the function and possibly the maturation of adenohypophyseal cells in vitro. Furthermore, although laminin is the most abundant component in Matrigel, the effects of Matrigel on lactotrophs and gonadotrophs in vitro are probably not attributable solely to its laminin content.


Alterations in elastin of the optic nerve head in human and experimental glaucoma.
The optic nerve heads from normal and glaucomatous eyes of humans and monkeys were examined by light and electron microscopy for the presence and distribution of elastin. Elastin densely lined the insertion of the lamina cribrosa into the sclera and was prominent in the laminar beams. The long axis of elastin paralleled that of the collagen fibrils and corresponded to the directions of expected forces on the tissue. In glaucomatous eyes elastin molecules were curled instead of straight and seemed disconnected from the other elements of the connective tissue matrix. Laminar beams stretch and reorganise their substructure during glaucomatous atrophy, probably leading to changed compliance. Differences in elastin function may have a part in susceptibility to glaucomatous injury.


Steroid Sulfatase Stimulates Intracrine Androgen Synthesis and is a Therapeutic Target for Advanced Prostate Cancer.
Most patients with prostate cancer receiving enzalutamide or abiraterone develop resistance. Clinical evidence indicates that serum levels of dehydroepiandrosterone sulfate (DHEAS) and biologically active DHEA remain in the high range despite antiandrogen treatment. The conversion of DHEAS into DHEA by steroid sulfatase (STS) may contribute to sustained intracrine androgen synthesis. Here, we determine the contribution of STS to treatment resistance and explore the potential of targeting STS to overcome resistance in prostate cancer. STS expression was examined in patients and cell lines. In vitro, STS activity and expression were modulated using STS-specific siRNA or novel STS inhibitors (STSi). Cell growth, colony formation, androgen production, and gene expression were examined. RNA-sequencing analysis was conducted on VCaP cells treated with STSi. Mice were treated with STSis with or without enzalutamide to determine their effects in vivo. STS is overexpressed in patients with castration-resistant prostate cancer (CRPC) and resistant cells. STS overexpression increases intracrine androgen synthesis, cell proliferation, and confers resistance to enzalutamide and abiraterone. Inhibition of STS using siRNA suppresses prostate cancer cell growth. Targeting STS activity using STSi inhibits STS activity, suppresses androgen receptor transcriptional activity, and reduces the growth of resistant C4-2B and VCaP prostate cancer cells. STSis significantly suppress resistant VCaP tumor growth, decrease serum PSA levels, and enhance enzalutamide treatment in vitro and in vivo. These studies suggest that STS drives intracrine androgen synthesis and prostate cancer proliferation. Targeting STS represents a therapeutic strategy to treat CRPC and improve second-generation antiandrogen therapy.


The Role of Genes and Environment in Degree of Partner Self-Similarity.
Choice of romantic partner is an enormously important component of human life, impacting almost every facet of day-to-day existence, however; the processes underlying this choice are remarkably complex and have so far been largely resistant to scientific explanation. One consistent finding is that, on average, members of romantic dyads tend to be more alike than would be expected by chance. Selecting for self-similarity is at least partially driven by phenotypic matching wherein couples share similar phenotypes, and preferences for a number of these traits are partly genetically influenced (e.g., education, height, social attitudes and religiosity). This suggests that genetically influenced preferences for self-similarity might contribute to phenotypic matching (and thus assortative mating), but it has never been studied in actual couples. In the present study, we use a large sample of twins to model sources of variation in self-similarity between partners. Biometrical modelling revealed that very little of the variation in the tendency to assortatively mate across 14 traits was due to genetic effects (7 %) or the shared environment of twins (0 %).


Summer birth and the deficit syndrome of schizophrenia.
Patients with the deficit syndrome differ from other patients with schizophrenia relative to physiological correlates, course of illness, and response to treatment. Because of the abnormal seasonality of birth among persons with schizophrenia, the authors examined the relation between this risk factor and the deficit syndrome. Findings in two clinical groups suggested an increase in summer births among deficit syndrome patients. The association between summer birth and the deficit syndrome was then examined in a catchment area study of first-admission patients with psychosis. In the catchment area sample, summer birth was also significantly associated with the deficit syndrome; negative symptoms broadly defined were not. These findings add to the increasing evidence that 1) patients with the deficit syndrome have a disease with an etiopathophysiology separate from that of other patients with what is now called schizophrenia and 2) the correlates of broadly defined negative symptoms are different from those for the deficit syndrome. The previously reported association between winter birth and schizophrenia appears to apply to nondeficit schizophrenia only.


Leishmania species: mechanisms of complement activation by five strains of promastigotes.
The interaction of fresh serum with promastigotes of Leishmania major, L. donovani, L. mexicana mexicana, L. mexicana amazonensis, and L. braziliensis guyanensis results in lysis of all strains tested with either fresh human or guinea pig serum at 37 C for 30 min. Lysis does not occur in the cold and requires divalent cations and complement that is active hemolytically. Serum deficient in the eighth component of complement is not lytic. Lysis of L. major, L. mexicana, and L. braziliensis proceeds fully in human serum containing EGTA/Mg2+ or in guinea pig serum deficient in the fourth complement component. These species consume only small amounts of C4 from human serum and do not require calcium to optimally bind C3. The data indicate that all are activators of the alternative complement pathway and that the classical pathway is not required for the lysis of these organisms. Promastigotes of L. donovani, in contrast, activate the classical pathway. The presence of calcium is required for both optimal C3 binding and parasite lysis, and L. donovani promastigotes consume C4 when incubated in human serum. In high concentrations, human serum agglutinates all tested Leishmania spp. The agglutinating factor does not require divalent cations, is heat stable, and works at 4 C, suggesting that it is an antibody. This "naturally occurring" antibody cross reacts with all Leishmania spp. and agglutinates them. The adsorption of serum with any Leishmania species or with beads that are Protein A coated, removes the agglutinogen. This factor causes a slight enhancement in alternative pathway activation by L. major and mediates the classical activation by L. donovani. In adsorbed serum, L. donovani promastigotes only weakly activate the alternative complement pathway. Increased concentrations of adsorbed serum are therefore necessary for lysis to proceed. The titer can be partially restored by the addition of heat inactivated serum. Using purified components of the classical cascade, we are unable to visualize surface bound C3 on L. donovani promastigotes unless heat inactivated serum is also present. We conclude that all Leishmania spp. promastigotes are susceptible to lysis by normal serum independent of antibody. The presence of small amounts of naturally occurring antibody in human serum enhances the susceptibility of L. donovani promastigotes to lysis by activating the classical complement pathway.


Ultrastructural modifications of cell membranes induced by "electroporation" on melanoma xenografts.
Electroporation (EP) has been widely employed in the past years as a safe and effective technique to drive drugs and DNA plasmids into target cells both for experimental and therapeutic purposes. Despite the large bulk of literature on this topic, often describing successful outcomes, there is a lack of knowledge about the intimate mechanism(s) controlling this phenomenon. In this paper, we describe a number of ultrastructural alterations in the cellular membranes following the exposure of orthotopic melanomas and red blood cells to trains of biphasic pulses. Specifically, melanoma xenografts grown in nude mice were subject to trains of eight biphasic pulses using an electric field of 1250 or 2450 V/cm, excised after 5 min and processed for electron microscopy. The freeze-fracturing analysis of both cell types evidenced defects in the dynamic assembly of lipids and proteins, which generate "areas with rough structure" and intensive clustering of intramembrane proteins. Such modifications could be the hallmarks of lipid and protein alterations, of protein cohesion reduction, and of changes in lipid orientation inside cell membranes, as postulated in several mathematical models applied to electroporation, and warrant further investigations.


Photochromic flow visualization for the investigation of artificial heart valves.
A new method for the investigation of hydrodynamics of artificial heart valves is presented. It is a method of flow visualisation. The photochromic flow visualization method is based on activation of color tracers in originally colorless photochromic solutions by pulse laser radiation during 10(-6)-10(-9) seconds. The tracer appears as a straight colored line, which subsequently is deformed by the flow. The methods known so far for the flow visualization give an insight on the general flow but do not provide quantitative data. The method mainly used, the LDA, permits measurements only in one point. The new method combines the precision of the LDA with the clarity of flow visualization.


Modeling Ductal Carcinoma In Situ (DCIS): An Overview of CISNET Model Approaches.
Ductal carcinoma in situ (DCIS) can be a precursor to invasive breast cancer. Since the advent of screening mammography in the 1980's, the incidence of DCIS has increased dramatically. The value of screen detection and treatment of DCIS, however, is a matter of controversy, as it is unclear the extent to which detection and treatment of DCIS prevents invasive disease and reduces breast cancer mortality. The aim of this paper is to provide an overview of existing Cancer Intervention and Surveillance Modelling Network (CISNET) modeling approaches for the natural history of DCIS, and to compare these to other modeling approaches reported in the literature. Five of the 6 CISNET models currently include DCIS. Most models assume that some, but not all, lesions progress to invasive cancer. The natural history of DCIS cannot be directly observed and the CISNET models differ in their assumptions and in the data sources used to estimate the DCIS model parameters. These model differences translate into variation in outcomes, such as the amount of overdiagnosis of DCIS, with estimates ranging from 34% to 72% for biennial screening from ages 50 to 74 y. The other models described in the literature also report a large range in outcomes, with progression rates varying from 20% to 91%. DCIS grade was not yet included in the CISNET models. In the future, DCIS data by grade from active surveillance trials, the development of predictive markers of progression probability, and evidence from other screening modalities, such as tomosynthesis, may be used to inform and improve the models' representation of DCIS, and might lead to convergence of the model estimates. Until then, the CISNET model results consistently show a considerable amount of overdiagnosis of DCIS, supporting the safety and value of observational trials for low-risk DCIS.


[Soybean GmGolS2-2 improves drought resistance of transgenic tobacco].
Galactinol synthase (GolS) genes play important roles in plant response to abiotic stress. In this research, the plant expression vector of soybean GmGolS2-2 gene was constructed and transformed into tobacco to study the drought tolerance of transgenic tobacco. A GmGolS2-2 gene with 975 bp coding sequence was cloned from soybean leaves by reverse transcription-polymerase chain reaction (RT-PCR). GmGolS2-2 was linked to the plant expression vector pRI101 by restriction enzyme sites Nde Ⅰ and EcoR Ⅰ, and transformed into tobacco by leaf disc method. Genomic DNA PCR and real-time PCR showed that three GmGolS2-2 transgenic tobacco plants were obtained. The growth status of GmGolS2-2 transgenic tobacco under drought stress was better than that of wild-type tobacco. After drought stress treatment, the electrolyte leakage and malondialdehyde content of transgenic tobacco were lower than those of wild-type tobacco, but the proline content and soluble sugar content were higher than those of wild-type tobacco. The results of real-time PCR showed that the heterologous expression of GmGolS2-2 increased the expression of stress-related genes NtERD10C and NtAQP1 in transgenic tobacco. The above results indicated that GmGolS2-2 improved drought resistance of transgenic tobacco.


Transfer of the human telomerase reverse transcriptase (TERT) gene into T lymphocytes results in extension of replicative potential.
In most human somatic cells telomeres progressively shorten with each cell division eventually leading to chromosomal instability and cell senescence. The loss of telomere repeats with cell divisions may also limit the replicative life span of antigen-specific T lymphocytes. Recent studies have shown that the replicative life span of various primary human cells can be prolonged by induced expression of the telomerase reverse transcriptase (hTERT) gene. To test whether introduction of hTERT can extend the life span of primary human T lymphocytes, naive CD8(+) T lymphocytes were transfected with retroviral vectors containing the hTERT gene. Transduced T-cell clones expressed high levels of telomerase and either maintained or elongated their telomere lengths upon culture for extended periods of time. Two of the transduced subclones retained a normal cloning efficiency for more than 170 population doublings (PDs). In contrast, T-cell clones transfected with control vectors exhibited progressive telomere length shortening and stopped proliferation at around 108 PDs. Telomerase-positive T clones had a normal 46,XY karyotype, maintained their cytotoxic properties, and showed very little staining for the apoptotic marker annexin-V. These results indicate that ectopic hTERT gene expression is capable of extending the replicative life span of primary human CD8(+) cytotoxic T lymphocytes. (Blood. 2001;98:597-603)


Control of heterologous hepatitis C virus infection in chimpanzees is associated with the quality of vaccine-induced peripheral T-helper immune response.
Prophylactic hepatitis C virus (HCV) vaccine trials with human volunteers are pending. There is an important need for immunological end points which correlate with vaccine efficacy and which do not involve invasive procedures, such as liver biopsies. By using a multicomponent DNA priming-protein boosting vaccine strategy, naïve chimpanzees were immunized against HCV structural proteins (core, E1, and E2) as well as a nonstructural (NS3) protein. Following immunization, exposure to the heterologous HCV 1b J4 subtype resulted in a peak of plasma viremia which was lower in both immunized animals. Compared to the naïve infection control and nine additional historical controls which became chronic, vaccinee 2 (Vac2) rapidly resolved the infection, while the other (Vac1) clearly controlled HCV infection. Immunization induced antibodies, peptide-specific gamma interferon (IFN-gamma), protein-specific lymphoproliferative responses, IFN-gamma, interleukin-2 (IL-2), and IL-4 T-helper responses in both vaccinees. However, the specificities were markedly different: Vac2 developed responses which were lower in magnitude than those of Vac1 but which were biased towards Th1-type cytokine responses for E1 and NS3. This proof-of-principle study in chimpanzees revealed that immunization with a combination of nonstructural and structural antigens elicited T-cell responses associated with an alteration of the course of infection. Our findings provide data to support the concept that the quality of the response to conserved epitopes and the specific nature of the peripheral T-helper immune response are likely pivotal factors influencing the control and clearance of HCV infection.


Unexpected, isolated activated partial thromboplastin time prolongation: A practical mini-review.
A common inquiry in coagulation laboratories is how to interpret an unexpected, isolated prolonged activated partial thromboplastin time (APTT). In this context, isolated means together with a normal prothrombin time (PT) and/or normal international normalized ratio (INR). This finding may lead to contact with laboratory doctors for further advice on a diagnostic strategy. Occasionally, the need for a diagnostic algorithm can be subacute, where surgery has to be postponed until an explanation for the isolated, prolonged APTT has been established. Activated partial thromboplastin time as a coagulation test was developed to monitor patients with hemophilia. Different APTT reagents display considerable differences in their sensitivity to deficiencies of coagulation factors. An isolated, prolonged APTT is seen in (a) individuals/patients with lupus anticoagulants, (b) patients in treatment with anticoagulants, mainly heparin, and (c) patients with deficiencies of specific coagulation factors. In this tutorial review, we summarize what may cause an isolated prolonged APTT and we present a simple diagnostic algorithm to differentiate between lupus anticoagulants (common) and factor deficiencies (rare). The identification of an isolated prolonged APTT as well as the underlying cause can be of the utmost importance in ensuring the correct therapeutic follow-up.


[Application of high technology in liver surgery].
The PlasmaJet, a modem device that provides a high energy flow of ionized gas which seals small blood and lymph vessels has been recently introduced into clinical practice. A comparative retrospective analysis of results of 59 liver surgery with the help of new surgical technologies and standard surgical technique was performed. Liver resection with the use of high technology was accompanied by significantly less intraoperative blood loss, as well as a significant decrease of postoperative complications.


Assessing Factors Influencing Commitment to a Disparities Reduction Intervention: Social Justice Attitudes and Organizational Mission.
This mixed-methods study aims to understand what the perceptions of leaders and healthcare professionals are regarding causes of disparities, cultural competence, and motivation before launching a disparity reduction project in hypertension care, contrasting perceptions in Federally Qualified Health Centers (FQHCs), and in a non-FQHC system. We interviewed leaders of six participating primary care systems and surveyed providers and staff. FQHC respondents reported more positive cultural competence attitudes and behavior, higher motivation to implement the project, and less concern about barriers to caring for disadvantaged patients than those in the non-FQHC practices; however, egalitarian beliefs were similar among all. Qualitative analysis suggested that the organizational missions of the FQHCs reflect their critical role in serving vulnerable populations. All system leaders were aware of the challenges of provider care to underserved groups, but comprehensive initiatives to address social determinants of health and improve cultural competence were still needed in both system types. The study provides insights into the perceptions and motivations of primary care organizational leaders and providers who are interested in improving chronic care. It also offers an example for care disparity programs to understand commitment and values of the participants for tailoring interventions and setting baseline for progress.


Communication: Simple self-correlation corrections to the Ragot-Cortona model of local correlation energy.
The Ragot-Cortona or RC model of local correlation energy [J. Chem. Phys. 121, 7671 (2004)] improves the standard local approximation in various respects. This letter aims at illustrating the origin of this improvement. To that aim, simple self-interaction corrected versions of the RC model are implemented, which involve local energy differences only. Several correlation functionals are selected for direct comparison using Hartree-Fock charge densities of atomic ions (H(-) to Ar). One of the self-interaction corrected versions of the RC model shows surprising improvements over the initial RC model. First, it dramatically improves the atomic correlation energies of atomic ions. Second, the impact on the contribution of the correlation energy to ionization potentials or electron affinities is still more convincing. In both cases, the accuracy achieved is close to or better than a selection of gradient-level functionals.


Unusual polymorphic ventricular tachycardia originating from the pulmonary artery.
We report a case about a 27-year-old healthy young male who developed syncope during exercise, which was subsequently identified to be attributable to non-sustained polymorphic ventricular tachycardia (VT). Occurrence of polymorphic VT was neither related to a prolonged QT interval nor a fixed short coupling interval. Standard examinations including echocardiography, coronary angiography, isoproterenol infusion study, and cardiac MRI showed no structural heart disease. On the electrophysiology study, activation mapping revealed that a discrete potential preceded the premature ventricular complex (PVC) triggered polymorphic VT, which was recorded just above the pulmonary valve. After radiofrequency ablation at this area, PVC and polymorphic VT disappeared and did not recur after a 2 month follow up.


Adiposity of Korean school-age children measured by national and international growth charts.
The study was conducted to explore adiposity levels of Korean children using body mass index (BMI) and comparing how three BMI charts define adiposity. The charts used were the growth standard of the Korean Centers for Disease Control and Prevention and the growth references of the World Health Organization and the International Obesity Task Force. The percentage of children at different adiposity levels varied depending on which chart was used. These discrepancies arose from the different cut-offs for adiposity and the different characteristics of the populations that were used to develop the charts. Research is needed to identify which growth charts and cut-offs for children are most associated with health risks in later life.


Hypertension Canada's 2018 Guidelines for Diagnosis, Risk Assessment, Prevention, and Treatment of Hypertension in Adults and Children.
Hypertension Canada provides annually updated, evidence-based guidelines for the diagnosis, assessment, prevention, and treatment of hypertension in adults and children. This year, the adult and pediatric guidelines are combined in one document. The new 2018 pregnancy-specific hypertension guidelines are published separately. For 2018, 5 new guidelines are introduced, and 1 existing guideline on the blood pressure thresholds and targets in the setting of thrombolysis for acute ischemic stroke is revised. The use of validated wrist devices for the estimation of blood pressure in individuals with large arm circumference is now included. Guidance is provided for the follow-up measurements of blood pressure, with the use of standardized methods and electronic (oscillometric) upper arm devices in individuals with hypertension, and either ambulatory blood pressure monitoring or home blood pressure monitoring in individuals with white coat effect. We specify that all individuals with hypertension should have an assessment of global cardiovascular risk to promote health behaviours that lower blood pressure. Finally, an angiotensin receptor-neprilysin inhibitor combination should be used in place of either an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in individuals with heart failure (with ejection fraction < 40%) who are symptomatic despite appropriate doses of guideline-directed heart failure therapies. The specific evidence and rationale underlying each of these guidelines are discussed.


Response to selenium by callus cultures derived from astragalus species.
Callus cultures were obtained from five selenium accumulator and three nonaccumulator species of Astragalus. Their morphological characteristics and their growth responses to light, sucrose, kinetin, and 2,4-dichlorophenoxyacetic acid are described. Calluses derived from accumulator species characteristically retained their tolerance to high concentrations of selenate and selenite, whereas calluses derived from nonaccumulator species were markedly inhibited by these two forms of selenium. Competition between sulfate and selenate was demonstrated. The two types of calluses could not be distinguished on the basis of (75)Se-labeled selenate or selenite uptake. Neutron activation analysis failed to show differences in selenium content between the two types of calluses grown on media to which no selenium had been added.


A Meta-Analysis of Breastfeeding Effects for Infants With Neonatal Abstinence Syndrome.
Neonatal abstinence syndrome (NAS) rates have dramatically increased. Breastfeeding is a nonpharmacological intervention that may be beneficial, reducing NAS symptom severity and thus the need for and duration of pharmacological treatment and length of hospital stay. Conduct meta-analysis to determine whether breastfeeding results in better outcomes for NAS infants. Variables included symptom severity, need for and duration of pharmacological treatment, and length of hospital stay. PubMed, Scopus, Embase, and Cochrane Library were searched from 2000 to 2020, and comparative studies examining breastfeeding for NAS infants were extracted. Randomized trials and cohort studies were included. Data were extracted and evaluated with Review Manager Version 5.3. A random-effects model was used to pool discontinuous outcomes using risk ratio and 95% confidence intervals. Continuous outcomes were evaluated by mean differences and 95% confidence intervals. Across 11 studies, 6,375 neonates were included in the meta-analysis. Using a random-effects analysis, breastfeeding reduced initiation of pharmacological treatment, reduced duration of pharmacological treatment, and reduced length of stay. No differences were detected for severity of NAS symptoms. Most studies only reported one to two variables of interest. For most studies, these variables were not the primary study outcomes. All studies were found to be of low risk and good quality based on the Cochrane Risk Assessment Tools. Varying breastfeeding definitions limit generalizability. Breastfeeding is associated with decreased initiation and duration of pharmacological treatment and length of stay.


Application of the OMERACT Grey-scale Ultrasound Scoring System for salivary glands in a single-centre cohort of patients with suspected Sjögren's syndrome.
To describe salivary gland involvement in patients suspected of Sjögren's syndrome (SS) using the OMERACT Ultrasound Scoring System for SS. Next, using different ultrasound cut-offs, to assess the performance of the scoring system for diagnosis and fulfilment of 2016 ACR/EULAR SS classification criteria. All patients referred to our department with a suspicion of SS in a 12-month period were included. All underwent grey-scale ultrasound of the parotid and submandibular glands prior to clinical examination, Schirmer's test, unstimulated salivary flow, blood samples including autoantibody analysis. Labial biopsy was performed according to clinicians' judgement. Images of the four glands were scored 0-3 according to the scoring system and a consensus score was obtained using a developed ultrasound atlas. Of the 134 patients included in the analysis, 43 were diagnosed with primary SS (pSS) and all fulfilled the 2016 American College of Rheumatology (ACR)/EULAR classification criteria. More patients with pSS compared with non-pSS had score ≥2 in at least one gland (72% vs 13%; p<0.001). In patients with score ≥2 in any gland, significantly more had positive autoantibodies, sialometry, Schirmer's test and positive labial biopsy compared with those with scores ≤1. The best ultrasound cut-off value for diagnosing pSS was ≥1 gland with a score ≥2 (sensitivity=0.72, specificity=0.91). The OMERACT Ultrasound Scoring System showed good sensitivity (0.72) and excellent specificity (0.91) for fulfilling 2016 ACR/EULAR criteria using cut-off score >2 in at least one gland. Our data supports the use of ultrasound for diagnosing pSS and supports incorporation of ultrasound in the classification criteria.


In vivo determination of the force of leukocyte-endothelium adhesion in the mesenteric microvasculature of the cat.
Quantitative estimates of the force of adhesion between leukocytes and endothelium were obtained from in vivo hemodynamic measurements in small venules of cat mesentery during topical application of the chemotactic compound N-formyl-methionyl-leucyl-phenylalanine (FMLP). Simultaneous measurements of upstream to downstream pressure drop, red cell velocity, microvessel hematocrit, and vessel diameter and length permitted application of the principles of momentum conservation to calculate the forces acting upon a leukocyte during adhesion to the endothelium. For venules ranging in diameter from 23 to 49 micron, the ratio of force (acting in the vessel axial direction) to wall shear stress on the endothelium fell from 14.6 X 10(-6) in small venules to 2.3 X 10(-6) dynes per dyne/cm2 in large venules; reflecting the larger pressure drops and forces attendant to greater lumen obstruction in the smaller venules. The equilibrium force representative of a balance between fluid shear stresses on the leukocyte and those at its site of contact with the endothelium ranged from 1.1 to 76.1 X 10(-5) dynes for wall shear stress ranging from 2 to 25 dynes/cm2; with venules with greater wall shear stresses having the greater leukocyte-endothelium shear force. Within individual venules, however, the force acting on a single leukocyte varied inversely with wall shear stress, most likely due to white blood cell deformation, which leads to a lessening of shear stress on the surface of the white blood cell.


Improving attention and managing attentional problems. Adapting rehabilitation techniques to adults with ADD.
Research and clinical experience in the field of brain injury rehabilitation have focused quite extensively on the need and potential to retrain attentional skills that are commonly affected by acquired brain injury. Four approaches to managing attention impairments that have emerged from this literature include attention process training, training use of strategies and environmental support, training use of external aids, and the provision of psychosocial support. Most often, several of these will be used in combination. For example, a therapy regimen might include attention process training emphasizing specific components of attention (e.g., sustained attention), in conjunction with training in pacing techniques, and psychosocial support, where the client keeps behavioral logs and discusses insights gained from tracking attention successes and attention lapses. Although there are as yet little data with regard to the effectiveness of these approaches in adults with developmental disorders of attention, there is a growing literature suggesting they may be effective in children and adolescents with ADHD. Further investigation of the application of such techniques in adults with a wide variety of attention disorders, including developmental disorders, would be valuable.


Aging in the three-dimensional random-field Ising model.
We studied the nonequilibrium aging behavior of the random-field Ising model in three dimensions for various values of the disorder strength. This allowed us to investigate how the aging behavior changes across the ferromagnetic-paramagnetic phase transition. We investigated a large system size of N=256^{3} spins and up to 10^{8} Monte Carlo sweeps. To reach these necessary long simulation times, we employed an implementation running on Intel Xeon Phi coprocessors, reaching single-spin-flip times as short as 6 ps. We measured typical correlation functions in space and time to extract a growing length scale and corresponding exponents.


The effect of preparation strategies, qualification and professional background on clinical nurse educator confidence.
To describe how clinical nurse educators (CliNEs) in Vietnam are prepared for their role; to identify which preparation strategies assist development of confidence in clinical teaching; and to measure the effect of educational qualifications and professional background on perceived confidence levels. The quality of clinical teaching can directly affect the quality of the student learning experience. The role of the clinical educator is complex and dynamic and requires a period of adjustment for successful role transition to occur. Planned orientation and specific preparation programmes assist transition and reduce anxiety for new CliNEs. There is, however, a lack of clear evidence to identify the form this preparation should take or which strategies are likely to facilitate the development of role confidence. Descriptive survey study. Cross-sectional surveys were used to collect data from 334 CliNEs during January-March 2015. Eight preparation methods commonly used in Vietnam were identified. There was a small yet significant association between preparation and CliNEs' perceived confidence. Formal preparation methods, and postgraduate qualifications and years of clinical teaching experience were linked to increased confidence in clinical teaching. Conversely, informal mentorship was found to hinder confidence development. This study identifies several preparation strategies that significantly enhance clinical educator confidence and readiness for their complex role. These preparation strategies drawn from the Vietnamese context, provide important examples for the wider nursing community to consider.


Pro- and antiarrhythmic effects of d-sotalol and dl-sotalol in an isolated tissue model of ischemia and reperfusion.
Pro- and antiarrhythmic effects of dl-sotalol and d-sotalol were compared with their electrophysiological actions in an isolated tissue model of simulated ischemia and reperfusion. Microelectrode recordings were made from endo- and epicardium of isolated guinea pig right ventricular free walls. An electrocardiogram also was recorded by two electrodes at opposite ends of the tissue bath. Regular stimulation was delivered to the endocardium. Tissues were exposed to simulated ischemia for 15 min and then were reperfused with normal Tyrode's solution. Arrhythmias with characteristics of transmural reentry occurred in 33% of hearts in ischemia and 73% of hearts in early reperfusion. Arrhythmias were accompanied by prolongation of transmural conduction time (CT) and abbreviation of endocardial action potential duration (APD) and effective refractory period. Both dl-sotalol and d-sotalol (100 microM) significantly (P < .05) prolonged endocardial APD, effective refractory period and epicardial APD under preischemic conditions; however, these effects were lost during simulated ischemia and early reperfusion. dl-Sotalol abolished arrhythmias in ischemia and reduced the incidence of reperfusion arrhythmias to 30%. This agent attenuated prolongation of transmural CT by ischemia and decreased the incidence of conduction block. In contrast, d-sotalol (100 microM) increased arrhythmias in ischemia to 80% and did not change the incidence of reperfusion arrhythmias (60%). The proarrhythmic effects of d-sotalol were accompanied by prolongation of transmural CT, increased incidence of conduction block and decreased epicardial excitability. Thus, in this model of global ischemia and reperfusion, antiarrhythmic effects were observed with dl-sotalol but not with the predominantly type III isomer, d-sotalol.


Inequities in exposure to occupational risk factors between Māori and non-Māori workers in Aotearoa New Zealand.
Health inequities between indigenous and non-indigenous people are well documented. However, the contribution of differential exposure to risk factors in the occupational environment remains unclear. This study assessed differences in the prevalence of self-reported exposure to disease risk factors, including dust and chemicals, physical factors and organisational factors, between Māori and non-Māori workers in New Zealand. Potential participants were sampled from the New Zealand electoral rolls and invited to take part in a telephone interview, which included questions about current workplace exposures. Logistic regression, accounting for differences in age, socioeconomic status and occupational distribution between Māori and non-Māori, was used to assess differences in exposures. In total, 2344 Māori and 2710 non-Māori participants were included in the analyses. Māori had greater exposure to occupational risk factors than non-Māori. For dust and chemical exposures, the main differences related to Māori working in occupations where these exposures are more common. However, even within the same job, Māori were more likely to be exposed to physical factors such as heavy lifting and loud noise, and organisational factors such as carrying out repetitive tasks and working to tight deadlines compared with non-Māori. This is one of the first studies internationally to compare occupational risk factors between indigenous and non-indigenous people. These findings suggest that the contribution of the occupational environment to health inequities between Māori and non-Māori has been underestimated and that work tasks may be unequally distributed according to ethnicity.


Development of a framework for the evidence-based choice of outcome measures in neurological physiotherapy.
Neurological physiotherapists recognize the need to include standardized outcome measures (OMs) in clinical practice but lack of information about the OMs available hampers utilization. This paper reports on the first stage of a project to identify the most robust OMs for use in neurological physiotherapy. To identify what physiotherapists perceive that they need to measure during a neurological assessment. Three separate workshops were held using patient vignettes to represent the acute, rehabilitation and community settings. Thirty senior neurological physiotherapists participated and were asked: 'What would you observe, test or measure if assessing this patient?' Data were analysed using thematic content analysis performed independently by each of the authors. Internal and external member checking ensured validity. In addition, the authors produced definitions of the items and domains identified in the data collection and subsequent content analysis. Items from the data collection were classified into 16 domains that physiotherapists need to measure: Weakness; range of movement/contracture; pain; muscle tone/spasticity; sensation; ataxia/co-ordination; personal fatigue; oedema; subluxation; postural and balance impairment; walking impairment; upper limb; balance disability; walking disability; mobility disability and falls. The domains that physiotherapists need to measure during clinical assessment were identified. In the second stage of the project these domains will inform systematic reviews to identify the most robust outcome measures for use in clinical practice.


La protein and its associated small nuclear and nucleolar precursor RNAs.
After transcription by RNA polymerase (pol) III, nascent Pol III transcripts pass through RNA processing, modification, and transport machineries as part of their posttranscriptional maturation process. The first factor to interact with Pol III transcripts is La protein, which binds principally via its conserved N-terminal domain (NTD), to the UUU-OH motif that results from transcription termination. This review includes a sequence Logo of the most conserved region of La and its refined modeling as an RNA recognition motif (RRM). La protects RNAs from 3' exonucleolytic digestion and also contributes to their nuclear retention. The variety of modifications found on La-associated RNAs is reviewed in detail and considered in the contexts of how La may bind the termini of structured RNAs without interfering with recognition by modification enzymes, and its ability to chaperone RNAs through multiple parts of their maturation pathways. The CTD of human La recognizes the 5' end region of nascent RNA in a manner that is sensitive to serine 366 phosphorylation. Although the CTD can control pre-tRNA cleavage by RNase P, a rate-limiting step in tRNASerUGA maturation, the extent to which it acts in the maturation pathway(s) of other transcripts is unknown but considered here. Evidence that a fraction of La resides in the nucleolus together with recent findings that several Pol III transcripts pass through the nucleolus is also reviewed. An imminent goal is to understand how the bipartite RNA binding, intracellular trafficking, and signal transduction activities of La are integrated with the maturation pathways of the various RNAs with which it associates.


Exercise and green tea extract stimulate fat oxidation and prevent obesity in mice.
The purpose of the present study was to explore the combined effects of dietary supplementation with green tea extract (GTE) and regular exercise on the development of obesity in high fat-fed C57BL/6J mice. Weight and age-matched male mice were divided into 5 groups of 10 mice each. Groups were treated as follows: a low-fat diet and not exercised (LF), a high-fat diet and not exercised (HF), a high-fat diet supplemented with GTE and not exercised (GTE-HF), a high-fat diet and exercised regularly (EX-HF), or a high-fat diet supplemented with GTE and exercised regularly (GTEEX-HF). The exercise modality was treadmill running. After 15 wk, GTE alone and regular exercise alone caused a 47 and 24% reduction in body weight gain induced by the high-fat diet, respectively, and when combined, resulted in an 89% reduction. In visceral fat accumulation, GTE alone, exercise alone, and their combination caused a 58, 37, and 87% reduction, respectively. Indirect calorimetry showed that the GTEEX-HF group had the highest energy expenditure and fat utilization in the sedentary condition after 4 wk. Furthermore, the GTEEX-HF group utilized more fat than the EX-HF group during exercise. GTE supplementation increased hepatic fatty acid oxidation both in the exercised and nonexercised groups. In addition, when combined with regular exercise, GTE supplementation also stimulated skeletal muscle fatty acid oxidation. In conclusion, dietary GTE and regular exercise, if combined, stimulate fat catabolism not only in the liver but also in skeletal muscle, and attenuate high-fat diet-induced obesity more effectively than each alone in C57BL/6J mice.


The association between gene polymorphisms in uncoupling proteins and hearing impairment in Japanese elderly.
This study illustrates that UCP2 Ala55Val polymorphisms exhibit a significant association with age-related hearing loss in the Japanese population. Mitochondrial uncoupling proteins (UCPs) have been suggested to play a protective role against neuron oxidative damage and a thermal signaling role in neuron modulation in the inner ear. In the current study, we examined the relationship between gene polymorphisms in UCP1 and UCP2 and hearing impairment (HI) in Japanese elderly. A total of 1547 subjects aged 40-79 years and living in Aichi prefecture, Japan, were entered into this study. Subjects were followed up every 2 years, and the cumulative number of subjects for 3 sequential examinations in 6 years was 4942 persons. Detailed questionnaires, pure-tone audiometry measurements, and UCP1 A-3826G and UCP2 Ala55Val polymorphisms were examined. Using generalized estimating equations, associations between HI and gene polymorphisms in UCP1 and UCP2 with age, sex, history of occupational noise exposure, and body mass index were analyzed under dominant, recessive, and additive models. UCP1 A-3826G polymorphism did not exhibit any significant association with HI. However, UCP2 Ala55Val polymorphism did exhibit a significant association with HI under all the dominant (p = 0.0167), recessive (p = 0.0411), and additive (p = 0.0061) models.


[Incidence of permanent disability in a cohort of social security-affiliated workers (2004-2007)].
To describe the incidence of permanent disability, both work-related and non-work-related, by several socioeconomic and geographical variables. We performed a retrospective study of a cohort of 768,454 workers covered by the General Social Security Regimen, followed-up from 2004 to 2007. This study was based on the Continuous Working Life Survey. In the 4 years of follow-up, 7,749 cases in 1,937,921 workers-years were identified. Incidence rates and crude and adjusted rate ratios were estimated by Poisson regression models. The incidence of non-work-related permanent disability was 10 times greater than that of work-related disability (36.3 versus 3.7 per 10,000 workers-years). The incidences for both non-work-related and work-related disability were higher in men and increased with age and lower education level. For non-work-related permanent disability, the region with the highest incidence was Asturias and that with the lowest was Madrid (56.7 vs. 23.3). For work-related permanent disability, the highest incidence was found in Asturias and the lowest in Navarre (7.8 vs. 1.4). This differential was maintained for work-related and non-work-related permanent disability for Asturias, after adjustment was made by sex, age, educational level, company size and economic activity. In this study, we observed substantial differences in the incidences of permanent disability by demographic, social and geographical characteristics, which should be analyzed in greater depth, especially the differences observed by regions.


Symptoms of depression, anxiety, and thoughts of suicide/self-injury in adolescents and young adults living with HIV in Botswana.
Globally, mental health problems have been reported to be more common in youth living with HIV (YLWH) than in the general population, but routine mental health screening is rarely done in high-volume HIV clinics. In 2019, YLWH in a large HIV clinic in Botswana were screened using the Generalized Anxiety Scale-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) in a pilot standard-of-care screening programme. Two-way ANOVA was used to describe the effects of age group (12-<16, 16-<20 and 20-25 years old) and sex on GAD-7 and PHQ-9 scores. Chi-square statistics were used to compare characteristics of YLWH with and without potential suicidality/self-harm symptoms based on question 9 in the PHQ-9. Among 1 469 YLWH, 33.1%, 44.3% and 15.0% had anxiety, depression and potential suicidality/self-harm symptoms respectively. YLWH of 20-25 years old and 16-<20 years old had higher GAD-7 scores compared to 12-<16-year-olds (p = 0.014 and p = <0.001 respectively). Female YLWH of 20-25 years old had higher PHQ-9 scores compared to 12-<16-year-olds (p = 0.002). There were no other sex-age dynamics that were statistically significant. Female YLWH endorsed more thoughts of suicidality/self-harm than males (17% versus 13%, p = 0.03 respectively). Given the proportion of YLWH with mental health symptoms, Botswana should enhance investments in mental health services for YLWH, especially for young female adults who bear a disproportionate burden.


Cefiderocol- Compared to Colistin-Based Regimens for the Treatment of Severe Infections Caused by Carbapenem-Resistant Acinetobacter baumannii.
Cefiderocol may represent a therapeutic option for carbapenem-resistant Acinetobacter baumannii (CRAB) infections, but clinical data are limited. This is an observational retrospective study conducted in the University Hospital of Pisa including consecutive patients with CRAB infections (January 2020 to August 2021). Patients were divided in two study groups according to the antibiotic treatment received: cefiderocol- and colistin-containing regimens. The primary outcome was the 30-day mortality. A Cox regression analysis was performed to identify factors independently associated with 30-day mortality. A propensity score analysis using inverse probability of treatment weighting (IPTW) was also performed. A total of 124 patients were included: 47 (37.9%) received cefiderocol, while 77 (62.1%) colistin-containing regimens. Overall, 79 (63.7%) patients had a bloodstream infection (BSI), 35 (28.5%) a ventilator-associated pneumonia (VAP) and 10 (8.1%) other infections. Thirty-day mortality was higher in patients receiving colistin- compared to those who received cefiderocol-containing regimens (55.8% versus 34%, P = 0.018). This difference was confirmed in patients with BSI, but not in those with VAP. On multivariable analysis, septic shock, SOFA score, and age were independently associated with 30-day mortality, while cefiderocol therapy was protective in an IPTW analysis (Hazard ratio 0.44, 95% confidence interval 0.22-0.66, P < 0.001). Nephrotoxicity was more common in the colistin group. Microbiological failure occurred in 17.4% of patients receiving cefiderocol versus 6.8% of those receiving colistin (P = 0.079). Among 8 cases in the cefiderocol group who experienced microbiological failure, 4 (50%) developed resistance to cefiderocol. Cefiderocol represents a promising therapeutic option in patients with severe CRAB infections. Randomized clinical trial in this specific patient population should confirm our findings.


Effects of mental imagery styles on shoulder and hip rotations during preparation of pirouettes.
To analyze individual behavior in spatial navigation especially for pirouette preparations (complete whole-body rotations), the authors studied horizontal shoulder-hip interactions under 2 constraints: postural (right and left supporting legs [SL]) and spatial (clockwise [CW] and counterclockwise [CCW]). They performed kinematic analysis at the start and end of the shoulder-hip horizontal rotations (run-up) with regard to imagery of motor actions. On the basis of the Vividness of Movement Imagery Questionnaire, they classified 8 female expert ballet dancers and 7 untrained female participants according to their movement imagery style (kinesthetic and visual). At the run-up's end, the shoulders initiated the turn independently of SL but differently depending on training: CW for dancers and CCW for untrained participants (their commonly used direction). Kinesthetic and mixed imagery styles prevailed in dancers, whereas simply a mixed style appeared among untrained participants. Thus, dance training enhances the imagery of kinesthetic sensation and influences the choice of spatial direction, facilitating the body-space interaction.


Performance of Given suspected blood indicator.
Given Imaging (Yoqneam, Israel) has developed a suspected blood indicator (SBI) function for its wireless capsule endoscopy (WCE) software. The SBI detects blood and marks appropriate images for interrogation. The sensitivity and accuracy of SBI and its role in examining WCE studies is unknown. Our aim was to evaluate the accuracy of this new software in detecting small bowel lesions. WCE reports of all patients referred for WCE in October and November, 2002, were reviewed. The images from each patient were reviewed by experienced gastroenterologists at 15 frames/s. The findings detected by gastroenterologists were compared to those recognized by SBI. Arteriovenous malformations (AVMs), ulcers, erosions, and sites of active bleeding were considered significant lesions. A total of 24 patients (16 women and eight men, mean age 59 yr) were studied during this period. The indications for the study were iron deficiency anemia in 18 patients and abdominal pain in six patients. A total of 109 lesions were identified by gastroenterologists (47 AVMs, 18 active bleeding ulcers, 18 ulcers without bleeding, and 26 erosions). Active bleeding seen by gastroenterologists was secondary to AVMs (five cases), jejunal ulcers (11 cases, all in the same patient), and gastric ulcers (two cases). A total of 31 potential areas of blood were identified by SBI. When compared to those findings recognized by gastroenterologists, 28 lesions were correctly identified (six AVMs, 13 active bleeding ulcers, (three AVMs and 10 jejunal ulcers), seven nonbleeding ulcers, and two nonbleeding erosions. The overall sensitivity, positive predictive value, and accuracy of SBI to detect significant small bowel lesions were 25.7%, 90%, and 34.8%, respectively. If only actively bleeding lesions in the small bowel were considered, SBI had sensitivity, positive predictive value, and accuracy of 81.2%, 81.3%, and 83.3%, respectively. SBI has good sensitivity and positive predictive value for actively bleeding lesions in the small bowel. Complete review of the study by the physician is still needed. SBI should be considered as a complementary and rapid screening tool for gastroenterologists to identify actively bleeding lesions.


[The temporomandibular joint].
With its discordant articular surfaces and complete division in two cavities separated by a disk, the temporomandibular joint appears as a complex anatomical and functional entity. Combined movements involving anteroposterior gliding between the disk and temporal bone in the upper cavity, anteroposterior condyle translation, hinge and rotation movements between the disk and mandibular condyle contribute to the different movements of the jaw. With dental occlusion, the masticatory apparatus therefore includes five functionally coordinated articular compartments. Various impairments of the normal static and dynamic features of the temporomandibular joint may lead to relatively frequent pathological conditions which can be easily diagnosed by modern imaging and arthroscopic methods.


Neuroprotective Drug Therapy: A Medical and Pharmacological Treatment for Tinnitus Control.
The role of neuroprotective agents for maintaining or improving inner ear function, specifically for the symptom of tinnitus, is presented on the basis of neurootological, neurological, and neurosurgical clinical experiences. These clinical experiences involved the use of calcium channel blockers, free radical scavengers, corticosteroids, antagonists of glutamate at N-methyl-D-aspartate (NMDA) and non-NMDA receptors, and various thrombolytic agents for the etiologies of ischemia, trauma, and hemorrhage. A pharmacological basis for such drug efficacy includes a property described as neuroprotection. A pathology-based protocol for drug selection is proposed for tinnitus control. The goal of this article is to introduce to the neurootologist or otologist and other professionals attempting tinnitus control neuroprotective drug therapies that are being applied to such central nervous system pathological processes as ischemia, trauma, hemorrhage, and neurodegeneration. The innovative application of such drug therapies for treating the symptom of tinnitus of the severe disabling type is considered. The use of neuroprotective drugs in intratympanic drug therapy via the round window, for treatment of inner ear complaints of hearing loss, tinnitus, and vertigo, is discussed.


An in vitro model for vitamin A transport across the human blood-brain barrier.
Vitamin A, supplied by the diet, is critical for brain health, but little is known about its delivery across the blood-brain barrier (BBB). Brain microvascular endothelial-like cells (BMECs) differentiated from human-derived induced pluripotent stem cells (iPSC) form a tight barrier that recapitulates many of the properties of the human BBB. We paired iPSC-derived BMECs with recombinant vitamin A serum transport proteins, retinol binding protein (RBP) and transthyretin (TTR), to create an in vitro model for the study of vitamin A (retinol) delivery across the human BBB. iPSC-derived BMECs display a strong barrier phenotype, express key vitamin A metabolism markers and can be used for quantitative modeling of retinol accumulation and permeation. Manipulation of retinol, RBP and TTR concentrations, and the use of mutant RBP and TTR, yielded novel insights into the patterns of retinol accumulation in, and permeation across, the BBB. The results described herein provide a platform for deeper exploration of the regulatory mechanisms of retinol trafficking to the human brain.


Understanding crop genetic diversity under modern plant breeding.
Maximizing crop yield while at the same time minimizing crop failure for sustainable agriculture requires a better understanding of the impacts of plant breeding on crop genetic diversity. This review identifies knowledge gaps and shows the need for more research into genetic diversity changes under plant breeding. Modern plant breeding has made a profound impact on food production and will continue to play a vital role in world food security. For sustainable agriculture, a compromise should be sought between maximizing crop yield under changing climate and minimizing crop failure under unfavorable conditions. Such a compromise requires better understanding of the impacts of plant breeding on crop genetic diversity. Efforts have been made over the last three decades to assess crop genetic diversity using molecular marker technologies. However, these assessments have revealed some temporal diversity patterns that are largely inconsistent with our perception that modern plant breeding reduces crop genetic diversity. An attempt was made in this review to explain such discrepancies by examining empirical assessments of crop genetic diversity and theoretical investigations of genetic diversity changes over time under artificial selection. It was found that many crop genetic diversity assessments were not designed to assess diversity impacts from specific plant breeding programs, while others were experimentally inadequate and contained technical biases from the sampling of cultivars and genomes. Little attention has been paid to theoretical investigations on crop genetic diversity changes from plant breeding. A computer simulation of five simplified breeding schemes showed the substantial effects of plant breeding on the retention of heterozygosity over generations. It is clear that more efforts are needed to investigate crop genetic diversity in space and time under plant breeding to achieve sustainable crop production.


Super-resolution Mapping of Enhanced Emission by Collective Plasmonic Resonances.
Plasmonic particle arrays have remarkable optical properties originating from their collective behavior, which results in resonances with narrow line widths and enhanced electric fields extending far into the surrounding medium. Such resonances can be exploited for applications in strong light-matter coupling, sensing, light harvesting, nonlinear nanophotonics, lasing, and solid-state lighting. However, as the lattice constants associated with plasmonic particle arrays are on the order of their resonance wavelengths, mapping the interaction between point dipoles and plasmonic particle arrays cannot be done with diffraction-limited methods. Here, we map the enhanced emission of single fluorescent molecules coupled to a plasmonic particle array with ∼20 nm in-plane resolution by using stochastic super-resolution microscopy. We find that extended lattice resonances have minimal influence on the spontaneous decay rate of an emitter but instead can be exploited to enhance the outcoupling and directivity of the emission. Our results can guide the rational design of future optical devices based on plasmonic particle arrays.


[Anti-inflammatory activity of olive seed polyphenolic extract in the THP1-XBLUE-CD14 human monocytes cell line].
The aim of this study was to assess the anti-inflammatory activity of a polyphenolic extract from olive pits. The THP1-XBlue-CD14 (invivogen) cellular line, 80,000 cells/well, was incubated and inflammation (activation of NF-kb) was produced with 0.1 mg/mL of LPS (lipopolysaccharide from E. coli) for 24 hours. We assessed the presence of the extract (10 and 50 mg/L, biologically safe concentrations) for 2 hours at 37º C, before (preventive effect) and after (therapeutic effect) the proinflammatory activation, and the activity of alkaline phosphatase, which is expressed under the control of the NF-kb transcriptional factor, was quantified by colorimetry. The percentage of activity of NF-kb as preventive effect and therapeutic effect was assessed by comparing it to control cultures of cells with LPS and without extract, which are considered 100% of NF-kb. The preventive anti-inflammatory capacity of the extract at 50 mg/L was 25.5% (95% CI: 16.8-34.2) and the therapeutic effect 34.9% (95% CI: 25.3-44.4) for the same concentration, without any significant activity at 10 mg/L. An activity of polyphenols extracted from olive pits is shown, both in preventing inflammation and therapeutically eliminating inflammation through inhibition of NF-kB factor previously activated by LPS at concentrations of 50 mg/L of polyphenols, which previously haven been shown to be safe.


HLA-DPB1 DNA polymorphism in the Swiss population: linkage disequilibrium with other HLA loci and population genetic affinities.
Allelic diversity at the HLA-DPB1 locus was determined by PCR-oligotyping in a sample of 125 healthy Swiss individuals. A total of 17 alleles were detected among which four main alleles (DPB1*0401, *0201, *0301, *0402) reached a cumulative frequency of 74.8%. HLA-A and -B (by serology) and HLA-DRB1 (by oligotyping) allelic polymorphisms were analysed also. HLA-B and HLA-DRB1 loci were highly polymorphic with 25 and 28 alleles respectively and similar heterozygosity levels of 0.93 and 0.92. These two loci were found to be more polymorphic than expected under neutrality, while lower heterozygosity levels were found for HLA-A (0.87) and DPB1 (0.81) loci. This paper presents also a global comparison of DPB1 allelic frequencies among 15 populations from four continents. As opposed to the DRB1 locus, overall DPB1 is shown to have a lower level of polymorphism and may be considered as neutral in all tested populations. DPB1 genetic diversity is correlated significantly with geography also, as found previously for DRB1. Two- and four-locus haplotype frequencies were determined and the significance of their linkage disequilibrium tested by an original non-parametric method. A significant positive linkage disequilibrium was found for 11 A-B, 16 B-DRB1, 7 DRB1-DPB1 and 3 A-B-DRB1-DPB1 haplotypes. The overall linkage disequilibrium between DRB1 and DPB1 was much lower than expected from the physical distance and lower than for A-B and B-DRB1 pairs. The implications of these results for bone marrow transplantation and for the evolution of HLA loci are discussed.


Febrile Seizures Cause Depression and Anxiogenic Behaviors in Rats.
Febrile seizure (FS) is a common type of seizure occurring in human during infancy and childhood. Although an epileptic seizure is associated with psychiatric disorders and comorbid diseases such as depression, anxiety, autism spectrum disorders, sleep disorders, attention deficits, cognitive impairment, and migraine, the causal relationship between FS and psychiatric disorders is poorly understood. The objective of the current study was to investigate the relationship of FS occurrence in childhood with the pathogenesis of anxiety disorder and depression using an FS rat model. We induced febrile seizures in infantile rats (11 days postnatal) using a mercury vapor lamp. At 3 weeks and 12 weeks after FS induction, we examined behaviors and recorded local field potentials (LFPs) to assess anxiety and depression disorder. Interestingly, after FS induction in infantile rats, anxiogenic behaviors and depression-like phenotypes were found in both adult and juvenile FS rats. The analysis of LFPs revealed that 4-7 Hz hippocampal theta rhythm, a neural oscillatory marker for anxiety disorder, was significantly increased in FS rats compared with their wild-type littermates. Taken together, our findings suggest that FS occurrence in infants is causally related to increased levels of anxiety-related behaviors and depression-like symptoms in juvenile and adult rodents.


Comparison study on statistical features of predicted secondary structures for protein structural class prediction: From content to position.
Many content-based statistical features of secondary structural elements (CBF-PSSEs) have been proposed and achieved promising results in protein structural class prediction, but until now position distribution of the successive occurrences of an element in predicted secondary structure sequences hasn't been used. It is necessary to extract some appropriate position-based features of the secondary structural elements for prediction task. We proposed some position-based features of predicted secondary structural elements (PBF-PSSEs) and assessed their intrinsic ability relative to the available CBF-PSSEs, which not only offers a systematic and quantitative experimental assessment of these statistical features, but also naturally complements the available comparison of the CBF-PSSEs. We also analyzed the performance of the CBF-PSSEs combined with the PBF-PSSE and further constructed a new combined feature set, PBF11CBF-PSSE. Based on these experiments, novel valuable guidelines for the use of PBF-PSSEs and CBF-PSSEs were obtained. PBF-PSSEs and CBF-PSSEs have a compelling impact on protein structural class prediction. When combining with the PBF-PSSE, most of the CBF-PSSEs get a great improvement over the prediction accuracies, so the PBF-PSSEs and the CBF-PSSEs have to work closely so as to make significant and complementary contributions to protein structural class prediction. Besides, the proposed PBF-PSSE's performance is extremely sensitive to the choice of parameter k. In summary, our quantitative analysis verifies that exploring the position information of predicted secondary structural elements is a promising way to improve the abilities of protein structural class prediction.