COMMUNISM AND THE TRAUMA OF ITS COLLAPSE REVISITED.
This paper focuses on the intertwinement of society and the psyche as a consequence of 70 years of Communist rule and the trauma of its collapse in the 90's. The trauma had profound effects on the psyche. An empirical study that was carried out in 1996/1997, which compared the personality structure of adolescents from Russia and Austria, and a research dialogue in 1999, has been re-evaluated in the light of current political events. One aim that we had was to find out whether we could discover characteristic personality features, resulting from the Communist totalitarian society in Russia, as well as from the trauma of its collapse. This led to the development of the concepts of the "impersonal self" and the "denial mode". The Russians seemed to be frozen in a protective shell with "flat" affects. They were anxious, conflict avoidant, and somewhat lost. Ideas about missing adolescence and the importance of privacy are discussed. Society was shown to not only have intruded into the individual psyche, but also into the members of the intercultural research team in the form of projective identification. The importance of the interaction between society and the individual as a basic psychoanalytic concept dating back to Freud is elaborated. Finally, considerations pertaining to mental health and democracy are presented.


Regulation of activity of chloroperoxidase from Serratia marcescens.
The influence of various factors on the activity of chloroperoxidase from Serratia marcescens was investigated. The enzyme is active only in acetate-containing buffers within the pH range 4.2-5.8. F-, Cu2+, [Fe(CN)6]4+, and [Fe(CN)6]3+ inhibit the enzyme. The chloroperoxidase is thermostable and resistant to the effect of lower alcohols.


Qualification opinion of novel methodologies in the predementia stage of Alzheimer's disease: cerebro-spinal-fluid related biomarkers for drugs affecting amyloid burden--regulatory considerations by European Medicines Agency focusing in improving benefit/risk in regulatory trials.
The European Medicines Agency (EMA) in London is responsible for the Regulatory review of new medicinal products for Marketing Authorisation, through which pharmaceutical companies may obtain first Marketing Authorisation and subsequent Variations valid throughout the EU and EFTA. The qualification opinion of novel methodologies is a new procedure where applicants can obtain scientific advice on new methodologies for regulatory clinical trials of efficacy of new compounds. It will help benefit/risk assessment of the CHMP. The definition of prodromal AD is acceptable. The "Dubois Criteria" as criteria to define the population must be validated in full at the time of the submission of the dossiers. Including a positive CSF biomarker profile is considered predictive for the evaluation of the AD-dementia type. However, although high CSF tau and low CSF Aβ42 are predictive of Alzheimer's disease, the criterion "positive CSF tau/Aβ42 ratio" is not well defined. The qualification of biomarkers in the pre-dementia stage of Alzheimer's disease will allow better inclusion criteria of patients in pre-dementia trials in which the benefit/risk is higher for treatment with these novel compounds.


Mutants of Escherichia coli defective in membrane phospholipid synthesis. Properties of wild type and Km defective sn-glycerol-3-phosphate acyltransferase activities.
The sn-glycerol-3-phosphate (glycerol-P) acyltransferase, the first enzyme of membrane phospholipid synthesis in Escherichia coli, was investigated in a wild type and a mutant strain defective in this activity. The mutant strain, selected as a glycerol-P auxotroph, was previously shown to contain a glycerol-P acyltransferase activity with an apparent Km for glycerol-P 10 times higher than that of its parent or revertants. The membranous mutant glycerol-P acyltransferase but did not appear to be thermolabile in vivo. Revertants no longer requiring glycerol-P for growth, showed glycerol-P acyltransferase activity with thermolability properties similar to the wild type. The second phospholipid biosynthetic enzyme, 1-acylglycerol-P acyltransferase, was not thermolabile in membranes containing a thermolabile glycerol-P acyltransferase activity. The pH optimum for the mutant acyltransferase was over 1 pH unit higher than that of the parental activity. Further, the mutant and wild type glycerol-P acyltransferase differed in their response to magnesium chloride and potassium chloride. The palmitoyl-CoA dependence of the wild type and mutant glycerol-P acyltransferase activities were different. The mutant glycerol-P acyltransferase activity was inhibited greater than 90% by Triton X-100 under conditions where the wild type activity was not affected. These experiments provide novel information about the wild type glycerol-P acyltransferase activity of E. coli and provide six additional lines of evidence for the mutant character of the glycerol-P acyltransferase in the mutant strains.


Accumbens activity during a multiple schedule for water and sucrose reinforcement in rats.
Electrophysiological recording procedures were used to examine nucleus accumbens (Acb) cell firing during operant responding for water reinforcement vs. a highly palatable sweet solution (0.6 M sucrose). Rats (n = 8) were trained on a multiple schedule to press one lever for water (fixed ratio 1, FR1; 15 min) followed by a 20-sec timeout period (chamber dark, levers retracted), and extension of a second spatially distinct lever that the animals pressed for sucrose reinforcement (FR1; 15 min). Of 84 cells, 55 neurons (65%) displayed one of three types of patterned discharges (increases or decreases in firing rate) immediately before or following the sucrose- or water-reinforced response. The major finding of this report was that the majority of these neurons (36/55 cells; 65%) showed similar types of neuronal firing patterns across the two reinforcer conditions. The remaining cells (19/55; 35%) exhibited patterned activity specific to responding for one reinforcer only (water or sucrose). These findings are discussed with respect to how Acb neurons encode goal-directed behaviors for "natural" reinforcers including food, water, and a palatable sweet solution.


When a corrigendum is not sufficient.
We present the reasoning behind a retraction noting that even small, honest errors can result in significant changes in findings.


Physical activity in surgical lung cancer patients: a systematic review.
Perioperative exercise could improve health outcomes of surgical lung cancer patients, but less is known about their natural physical activity (PA) behavior before exercise interventions. This review aimed to synthesize evidence on PA, regarding the following: (1) proportion of patients meeting PA guidelines, (2) amount of PA, (3) PA trajectory following surgery, and (4) correlates of PA before or after surgery. We conducted a systematic review using PubMed, CINHAL, Scopus, and SPORTDiscus (July 2021). Observational or experimental studies that measure PA of lung cancer patients before/after surgery were included. We assessed methodological quality using the NIH Quality Assessment Tools and extracted data using a standardized form. Seventeen studies (25 articles, N = 1737 participants) published between 2009 and 2021 were included. Fourteen studies had sample sizes less than 100. Thirteen studies were of fair quality and four studies were of good quality. Only 23-28% of patients met PA guideline (150 min/week moderate-vigorous PA) at 6 months-6 years after surgery. Patients took an average of 3822-10,603 daily steps before surgery and 3934-8863 steps at 1-3 months after surgery. Physical activity was lower at 1 day-3 months after surgery, compared with preoperative levels. Perioperative PA was positively associated with exercise capacity, quality of life and reduced postoperative complications. This review suggests that PA is low among surgical lung cancer patients, and it may not recover within 3 months following surgery. Physical activity has the potential to improve postoperative outcomes. However, the existing evidence is weak, and future larger longitudinal studies are needed.


Selection and Application of DNA Aptamer Against Oncogene Amplified in Breast Cancer 1.
Amplified in breast cancer 1 (AIB1), also known as steroid receptor coactivator 3 (SRC-3), is a transcriptional coactivator that interacts with nuclear receptors and other transcription factors to enhance their effects on target gene transcription. AIB1, which acts as a major oncogene, is highly expressed in many human cancers, and has been demonstrated to be a key regulator for tumor initiation, progression, metastasis, invasion, and survival. Recruitment of the transcriptional factor CBP/p300 by CBP/p300-interaction domain (CID) of AIB1 is essential for its transcriptional activation function. In this research, we isolated a DNA aptamer AY-3 that binds to AIB1-CID from a random oligonucleotide library using in vitro screening technology-Systematic Evolution of Ligands by EXponential enrichment (SELEX). The binding affinity of the aptamer to AIB1-CID fusion protein is in the nanomolar range. More importantly, the aptamer was found to disrupt in the interaction between p300 and AIB1. This aptamer has great potential to serve as a therapeutic agent for cancer by inhibiting the coactivation of AIB1.


Painful extensor digitorum brevis manus muscle.
Diagnosis was confirmed of 10 extensor digitorum brevis manus muscles in 7 patients. The muscle is located on the dorsum of the hand, just distal to the wrist. It is most prominent with the wrist flexed to 30 degrees and the fingers fully extended. We propose that pain in the extensor digitorum brevis manus muscle is due to compression of the muscle in the rigid fibro-osseous fourth dorsal compartment. Extensor retinacular release is the treatment of choice.


"It helps us say what's important..." Developing Serious Illness Topics: A clinical visit agenda-setting tool.
Skillful communication with attention to patient and care partner priorities can help people with serious illnesses. Few patient-facing agenda-setting tools exist to facilitate such communication. To develop a tool to facilitate prioritization of patient and care partner concerns during serious illness visits. Two family members of seriously ill individuals advised. We performed a literature review and developed a prototype agenda-setting tool. We modified the tool based on cognitive interviews with patients, families and clinicians. We piloted the tool with patients, care partners and clinicians to gain an initial impression of its perceived value. Interviews with eight patients, eight care partners and seven clinicians, resulted in refinements to the initial tool, including supplementation with visual cues. In the pilot test, seven clinicians used the tool with 11 patients and 12 family members. Qualitatively, patients and care partners reported the guide helped them consider and assert their priorities. Clinicians reported the tool complemented usual practice. Most participants reported no distress, disruption or confusion. Patients, care partners and clinicians appreciated centering patient priorities in serious illness visits using the agenda-setting tool. More thorough evaluation is required. The agenda-setting tool may operationalize elements of good serious illness care.


DAnTE: a statistical tool for quantitative analysis of -omics data.
Data Analysis Tool Extension (DAnTE) is a statistical tool designed to address challenges associated with quantitative bottom-up, shotgun proteomics data. This tool has also been demonstrated for microarray data and can easily be extended to other high-throughput data types. DAnTE features selected normalization methods, missing value imputation algorithms, peptide-to-protein rollup methods, an extensive array of plotting functions and a comprehensive hypothesis-testing scheme that can handle unbalanced data and random effects. The graphical user interface (GUI) is designed to be very intuitive and user friendly. DAnTE may be downloaded free of charge at http://omics.pnl.gov/software/. An example dataset with instructions on how to perform a series of analysis steps is available at http://omics.pnl.gov/software/


Construction of developmentally inspired periosteum-like tissue for bone regeneration.
The periosteum, a highly vascularized thin tissue, has excellent osteogenic and bone regenerative abilities. The generation of periosteum-mimicking tissue has become a novel strategy for bone defect repair and regeneration, especially in critical-sized bone defects caused by trauma and bone tumor resection. Here, we utilized a bone morphogenetic protein-2 (BMP-2)-loaded scaffold to create periosteum-like tissue (PT) in vivo, mimicking the mesenchymal condensation during native long bone development. We found that BMP-2-induced endochondral ossification plays an indispensable role in the construction of PTs. Moreover, we confirmed that BMP-2-induced PTs exhibit a similar architecture to the periosteum and harbor abundant functional periosteum-like tissue-derived cells (PTDCs), blood vessels, and osteochondral progenitor cells. Interestingly, we found that the addition of chondroitin sulfate (CS), an essential component of the extracellular matrix (ECM), could further increase the abundance and enhance the function of recruited PTDCs from the PTs and finally increase the regenerative capacity of the PTs in autologous transplantation assays, even in old mice. This novel biomimetic strategy for generating PT through in vivo endochondral ossification deserves further clinical translation.


Maternal Testosterone Excess Contributes to Reproductive System Dysfunction of Female Offspring Mice.
Hyperandrogenism is considered 1 of the most important characteristics of polycystic ovary syndrome, which affects more than 10% of females of reproductive age and is a common cause of infertility. In addition to the effects on patients themselves, maternal androgen excess has also been reported to impair the growth and development of offspring. In our current study, we found that maternal testosterone (T) treatment during different gestational stages increased the percentage of atretic follicle and decreased corpus luteum formation in female offspring. In addition, decreased serum estradiol and increased T levels were also observed in female offspring of T-treated mice during late gestational stage. Further studies revealed that Forkhead box protein L2 (FOXL2) and Cytochrome P450 family 19 subfamily a member 1 (CYP19A1) expression in granulosa cells of these female offspring mice were decreased. By using mouse primary granulosa cells and the KGN cell line, we demonstrated that decreasing FOXL2 and CYP19A1 levels in ovarian granulosa cells partially may contribute to disturbed sex hormone synthesis in female offspring of T-treated mice during the late gestational stage. Findings from our current study highlight a critical role of excess maternal T exposure, especially during the late gestational stage, which could further lead to aberrant ovary development and sex hormone synthesis in female offspring.


Subgroups of depressive symptoms in Korean police officers: A latent class analysis.
The prevalence of depressive symptoms is common among police officers; however, studies that identify the patterns of depressive symptoms in police officers and occupational characteristics related to the specific subgroups of depressive symptoms are scarce. A total of 493 police officers in South Korea participated in this descriptive cross-sectional study between October and December 2019. Depressive symptoms were measured using the Patient Health Questionnaire-9. Latent class analysis was used to identify the subgroups of depressive symptoms. To identify the characteristics and predictors of the subgroup, χ2 tests, analysis of variance, and multinomial logistic regression analysis were performed. Four latent classes of depressive symptoms were identified: "at-risk" (10.8%), "anhedonic" (21.5%), "somatic" (17.2%), and "minimal" (50.5%). Compared to the minimal group, drinking behaviors were higher in the at-risk group (odds ratio [OR] = 1.10, 95% confidence interval [CI] [1.03, 1.11]), and working hours were greater in the somatic group (OR = 1.01, 95% CI [1.00, 1.02]). Additionally, sleep quality (OR = 1.35, 95% CI [0.82, 2.22]) and fatigue (OR = 1.02, 95% CI [1.00, 1.04]) were found to be related in the anhedonic group. This study identified the heterogeneity of depressive symptoms among police officers. It is necessary to accurately identify the factors associated with the depression subgroups of police officers to develop support strategies and prevent an increase in their depression severity. The association between risk factors such as working hours and drinking behaviors might inform strategies to reduce depression in police offers.


The effect of dissolved oxygen on the relaxation rates of blood plasma: Implications for hyperoxia calibrated BOLD.
To determine the contribution of paramagnetic dissolved oxygen in blood plasma to blood-oxygenation-level-dependent (BOLD) signal changes in hyperoxic calibrated BOLD studies. Bovine blood plasma samples were prepared with partial pressures of oxygen (pO2 ) ranging from 110 to 600 mmHg. R1 , R2 , and R2* of the plasma with dissolved oxygen were measured using quantitative MRI sequences at 3 Tesla. Simulations were performed to predict the relative effects of dissolved oxygen and deoxyhemoglobin changes in hyperoxia calibrated BOLD. The relaxivities of dissolved oxygen in plasma were found to be r1,O2 =1.97 ± 0.09 ×10-4 s-1 mmHg-1 , r2,O2 =2.3 ± 0.7 ×10-4 s-1 mmHg-1 , and r2,O2* = 2.3 ± 0.7 ×10-4 s-1 mmHg-1 . Simulations predict that neither the transverse nor longitudinal relaxation rates of dissolved oxygen contribute significantly to the BOLD signal during hyperoxia. During hyperoxia, the increases in R2 and R2* of blood from dissolved oxygen in plasma are considerably less than the decreases in R2 and R2* from venous deoxyhemoglobin. R1 effects due to dissolved oxygen are also predicted to be negligible. As a result, dissolved oxygen in arteries should not contribute significantly to the hyperoxic calibrated BOLD signal. Magn Reson Med 76:1905-1911, 2016. © 2015 International Society for Magnetic Resonance in Medicine.


Short-term effect of non-surgical periodontal treatment on local and systemic cytokine levels: Role of hyperglycemia.
The effect of non-surgical periodontal treatment on oral and systemic inflammatory mediators in subjects with periodontitis and hyperglycemia remains largely unknown. Therefore, the aim of this clinical study was to compare the short-term effect of non-surgical periodontal treatment on serum, saliva and GCF inflammatory markers levels in GP subjects with or without hyperglycemia. Sixty subjects divided into four groups of equal size were selected to participate: type 2 diabetics with generalized periodontitis (T2DM + GP), pre-diabetics with GP (PD + GP), normoglycemic subjects with GP (NG + GP), and healthy controls. GCF, serum, and saliva samples were obtained at baseline and 30 days after scaling and root planning (SRP) and the levels of interleukin-1β (IL-1 β), IL-8, IL-6, IL-2, IL-5, IL-4, IL-10, Interferon gamma (IFN-γ), Granulocyte macrophage colony-stimulating factor (GM-CSF) and Tumor necrosis factor-alpha (TNF-α) were determined by ultrasensitive multiplex assay. Clinical periodontal measurements were recorded. SRP yielded significant improvement of all periodontal parameters for all GP groups (p < 0.01). A significant reduction in GCF levels of several cytokines were observed; however, only IL-1B and IFN-γ were consistently reduced post-treatment across all GP groups. Salivary levels of IL-1β were significantly reduced in all GP groups following treatment. No significant differences were observed for serum levels after SRP. Periodontal treatment reduced local inflammatory markers, specifically IL-1B and IFN-γ, irrespective of the diabetes status. Periodontal treatment had no significant effect on serum levels of the inflammatory markers evaluated in this study.


Identification of evolutionarily invariant sequences in the protein C gene promoter.
Recent studies on human protein C gene expression have revealed the presence of three transcription factor binding sites in close proximity to the transcription start site. Binding sites for the liver-enriched hepatocyte nuclear factors 1 and 3 (HNF-1 and HNF-3, respectively) are located immediately upstream of the transcription start site, whereas just downstream of the start site a presently unidentified transcription factor may bind. To identify other candidate transcription factor binding sites in the protein C promoter, we studied the promoter sequence identity in a number of evolutionarily close and more distant species: Gorilla gorilla, Pongo pygmaeus, Pan troglodytes, Homo sapiens, Cebus apella, Macaca mulatta, Callithrix jacchus, Papio hamadryas, Macaca fascicularis, and Rattus norvegicus. This analysis showed that a high degree of identity (78%) exists among the different primates. Comparison of the primate consensus sequence with the Rattus norvegicus protein C promoter sequence revealed the presence of seven identical regions (I to VII). Two of these regions overlap with established regulatory sequences for HNF-3 and HNF-1 (region VI) and for PCE-1 (region VII), respectively. The functional importance and the transcription factors that may bind to the other five identical regions are now to be determined.


Herstellung von (S)-4-Methyloxetan-2-on(β-Butyrolacton) durch Lactonisierung von (R)-3-Hydroxy-buttersäure mit Orthoessigsäure-triethylester
The readily available (R)-3-hydroxybutanoic acid (1) was treated with triethyl orthoacetate, with azeotropic removal of ethanol, to yield (6R)-2-ethoxy-2,6-dimethyl-1,3-dioxan-4-one (3a). Pyrolysis of 3a led to the β-Lactone of (S)-3-hydroxybutanoic acid and other products. The influence of pressure, temperature, solvents, and some additives has been tested. A procedure for preparing (S)-4-methyloxetan-2-one (4) in a 0.25-mol scale is described.


Amygdalar vasopressin mRNA increases in acute cocaine withdrawal: evidence for opioid receptor modulation.
In humans, stress is recognized as a major factor contributing to relapse to drug abuse in abstinent individuals; drugs of abuse themselves or withdrawal from such drugs act as stressors. In the animals, evidence suggests that centrally released arginine vasopressin in both amygdala and hypothalamus plays an important role in stress-related anxiogenic behaviors. The stress responsive hypothalamic-pituitary-adrenal axis is under tonic inhibition via endogenous opioids, and cocaine withdrawal stimulates hypothalamic-pituitary-adrenal activity. The present studies were undertaken to determine whether: (1) 14-day (chronic) "binge" pattern cocaine administration (45 mg/kg/day) or its withdrawal for 3 h (acute), 1 day (subacute) or 10 days (chronic) alters arginine vasopressin mRNA levels in amygdala or hypothalamus; (2) the opioid receptor antagonist naloxone (1mg/kg) alters arginine vasopressin mRNA or hypothalamic-pituitary-adrenal hormonal responses in acute cocaine withdrawal; and (3) there are associated changes of mu opioid receptor or proopiomelanocortin mRNA levels. In amygdala, arginine vasopressin mRNA levels were unchanged after chronic "binge" cocaine, but were increased during acute cocaine withdrawal. Naloxone completely blocked this increase. Neither chronic cocaine nor its acute withdrawal altered amygdalar mu opioid receptor mRNA levels. The increase in amygdalar arginine vasopressin mRNA levels was still observed after subacute withdrawal, but not after chronic withdrawal. Although hypothalamic-pituitary-adrenal tolerance developed with chronic "binge" cocaine, there were modestly elevated plasma adrenocorticotropin hormone levels during acute withdrawal. While naloxone produced modest adrenocorticotropin hormone elevations in cocaine-naïve rats, naloxone failed to elicit an adrenocorticotropin hormone response in cocaine-withdrawn rats. In hypothalamus, neither chronic cocaine nor acute withdrawal altered arginine vasopressin, proopiomelanocortin or mu opioid receptor mRNA levels. These results show that: (1) opioid receptors mediate increased amygdalar arginine vasopressin gene expression during acute cocaine withdrawal, and (2) cocaine withdrawal renders the hypothalamic-pituitary-adrenal axis insensitive to naloxone. Our findings suggest a potential role for amygdalar arginine vasopressin in the aversive consequences of early cocaine withdrawal.


Cardioprotective Peptides from Milk Processing and Dairy Products: From Bioactivity to Final Products including Commercialization and Legislation.
Recent research has revealed the potential of peptides derived from dairy products preventing cardiovascular disorders, one of the main causes of death worldwide. This review provides an overview of the main cardioprotective effects (assayed in vitro, in vivo, and ex vivo) of bioactive peptides derived from different dairy processing methods (fermentation and enzymatic hydrolysis) and dairy products (yogurt, cheese, and kefir), as well as the beneficial or detrimental effects of the process of gastrointestinal digestion following oral consumption on the biological activities of dairy-derived peptides. The main literature available on the structure-function relationship of dairy bioactive peptides, such as molecular docking and quantitative structure-activity relationships, and their allergenicity and toxicity will also be covered together with the main legislative frameworks governing the commercialization of these compounds. The current products and companies currently commercializing their products as a source of bioactive peptides will also be summarized, emphasizing the main challenges and opportunities for the industrial exploitation of dairy bioactive peptides in the market of functional food and nutraceuticals.


Estimation of time-delayed mutual information and bias for irregularly and sparsely sampled time-series.
A method to estimate the time-dependent correlation via an empirical bias estimate of the time-delayed mutual information for a time-series is proposed. In particular, the bias of the time-delayed mutual information is shown to often be equivalent to the mutual information between two distributions of points from the same system separated by infinite time. Thus intuitively, estimation of the bias is reduced to estimation of the mutual information between distributions of data points separated by large time intervals. The proposed bias estimation techniques are shown to work for Lorenz equations data and glucose time series data of three patients from the Columbia University Medical Center database.


Clinical pilot study of different hand positions during manual chest compressions monitored with capnography.
Optimal hand position for chest compressions during cardiopulmonary resuscitation is unknown. Recent imaging studies indicate significant inter-individual anatomical variations, which might cause varying haemodynamic responses with standard chest compressions. This prospective clinical pilot study intended to assess the feasibility of utilizing capnography to optimize chest compressions and identify the optimal hand position. Intubated cardiac arrest patients treated by the physician manned ambulance between February and December 2011 monitored with continuous end-tidal CO2 (EtCO2) measurements were included. One minute of chest compressions at the inter-nipple line (INL) optimized using EtCO2 feedback, was followed by four 30-s intervals with compressions at four different sites; INL, 2 cm below the INL, 2 cm below and to the left of INL and 2 cm below and to the right of INL. Thirty patients were included. At the end of each 30-s interval median (range) EtCO2 was 3.1 kPa (0.7-8.7 kPa) at INL, 3.5 kPa (0.5-10.7) 2 cm below INL, 3.5 kPa (0.5-10.3 kPa) 2 cm below and to the left of INL, and 3.8 kPa (0.4-8.8 kPa) 2 cm below and to the right of INL (p=0.4). The EtCO2 difference within each subject between hand positions with maximum and minimum values varied between individuals from 0.2 to 3.4 kPa (median 0.9 kPa). Monitoring and optimizing chest compressions using capnography was feasible. We could not demonstrate one superior hand position, but inter-individual differences suggest optimal hand position might vary significantly among patients.


Molecular characterization of prolactin receptor (cPRLR) gene in chickens: gene structure, tissue expression, promoter analysis, and its interaction with chicken prolactin (cPRL) and prolactin-like protein (cPRL-L).
In this study, gene structure, tissue expression, and promoter usage of prolactin receptor (PRLR) and its interaction with prolactin (PRL) and the newly identified prolactin-like protein (PRL-L) were investigated in chickens. The results showed that (1) PRLR gene was found to consist of at least 25 exons by 5'-RACE and RT-PCR assays; (2) multiple PRLR 5'-UTR sequences different in exon composition were isolated from chicken liver or intestine by 5'-RACE and could be subdivided into type I and type II transcripts according to the first exon used (exon 1G or exon 1A); (3) PRLR Type I transcripts with exon 1G were detected to be predominantly expressed in adult kidney and small intestine by RT-PCR, implying their expression is likely controlled by a tissue-specific promoter (P1). By contrast, PRLR type II transcripts containing exon 1A are widely expressed in adult and embryonic tissues examined and their expression is controlled by a generic promoter (P2) near exon 1A, which was demonstrated to display promoter activities in cultured DF-1, HEK293 and LoVo cells by the dual-luciferase reporter assay; (4) Using a 5×STAT5-luciferase reporter system, cPRLR expressed in HepG2 cells was shown to be activated by recombinant cPRL and cPRL-L via interaction with PRLR membrane-proximal ligand-binding domain, suggesting that like cPRL, cPRL-L is also a functional ligand of cPRLR. Collectively, characterization of cPRLR gene helps to elucidate the roles of PRLR and its ligands in birds and provides insights into the regulatory mechanisms of PRLR expression conserved in birds and mammals.


Reward anticipation selectively boosts encoding of gist for visual objects.
Reward anticipation at encoding enhances later recognition, but it is unknown to what extent different levels of processing at encoding (gist vs. detail) can benefit from reward-related memory enhancement. In the current study, participants (N = 50) performed an incidental encoding task in which they made gist-related or detail-related judgments about pairs of visual objects while in anticipation of high or low reward. Results of a subsequent old/new recognition test revealed a reward-related memory benefit that was specific to objects from pairs encoded in the attention-to-gist condition. These findings are consistent with the theory of long-axis specialization along the human hippocampus, which localizes gist-based memory processes to the anterior hippocampus, a region highly interconnected with the dopaminergic reward network.


Genesis and profanation of the other world: The interpretation of dreams.
This paper addresses Nietzsche's reflections on the phenomenon of dreams as a crucial precedent of Freud's Die Traumdeutung. The works of Nietzsche and Freud are scrutinized to establish and compare the most relevant aspects of their understanding of dreams. The philosophical impact of both accounts is assessed in terms of the transvaluation of religious and metaphysical values, which reveals three epistemological shifts: the replacement of Metaphysics by History/Genealogy (Nietzsche) and by Metapsychology (Freud), and the expansion of rationality beyond the limits of consciousness (Nietzsche and Freud). Both authors are shown to consider dreams as figurative expressions of a postponed desire - or, more specifically, as the imaginary fulfillment (compensation) and the evocation/awakening of desire. As captured by the phrase "Memento libidines", dreams are portrayed in both accounts as the guardians of sleep and desire. Finally, and in contrast with Assoun, a new interpretation of Thus Spoke Zarathustra is proposed, as an interpretation of the prophet's dreams reveals the presence of individual desire within the Nietzschean understanding of the phenomenon.


Initial cardiovascular response on change of posture from squatting to standing.
The immediate cardiovascular responses on active change from the squatting (control) to the standing position differ from those obtained in the lying-to-standing manoeuvre. Without exception, the first beat after changing from squatting to standing showed a decrease in systolic, diastolic and mean pressure by 2.0 +/- 1.1 kPa (14.6 +/- 8.3 mm Hg), 1.4 +/- 1.7 kPa (10.6 +/- 12.6 mm Hg) and 1.9 +/- 1.0 kPa (13.9 +/- 7.3 mm Hg), respectively. During the 4th or 5th pulse after standing the pulse pressure was significantly higher than when lying (P less than 0.01). Mean pressure reached a minimum of 7.7 +/- 1.9 kPa (57.8 +/- 14.4 mm Hg) after 7.1 +/- 1.1 s. Thereafter the blood pressure increased to a new level within about 15 s. 11 of 16 subjects demonstrated a biphasic heart rate (HR) response. The maximum HR was reached after 11.0 +/- 2.4 s of standing. In all experiments, the peaks in HR were distinctly delayed after the blood pressure dips. We conclude that an arterial baroreflex could be implicated in the immediate HR increase after a squatting-to-standing manoeuvre. The subsequent time course of the initial HR response, however, might be induced by other mechanisms.


Similar architectures of native and transformed human alpha2-macroglobulin suggest the transformation mechanism.
The refined three-dimensional structure of native human alpha2-macroglobulin (alpha2M) has been determined by cryoelectron microscopy and three-dimensional reconstruction. New features corresponding to "sigmoid arches," "basal bodies," and "apical connections" were observed in the molecule. Since similar elements are found in the architecture of transformed alpha2M, the 2 volumes were aligned in three dimensions. In their common orientations, they show many similarities except near the openings of the central chamber. In the native conformation, these apertures are fully opened, allowing the proteases to access the central chamber of the molecule, while in the transformed structure, they are partially closed. These structures suggest that alpha2M conformational change involves a strong lateral compression and a vertical stretching of the native particle seen in its four-petaled flower view to produce the H view of the transformed form. A model of structural transformation, in which all the parts of the alpha2M molecule seem involved in the entrapment of the proteinases is proposed.


Multivariate factorial analysis to design a robust batch leaching test to assess the volcanic ash geochemical hazard.
A method to obtain robust information on short term leaching behaviour of volcanic ashes has been developed independently on the sample age. A mixed factorial design (MFD) was employed as a multivariate strategy for the evaluation of the effects of selected control factors and their interactions (amount of sample (A), contact time (B), and liquid to solid ratio or L/S (C)) on the leaching process of selected metals (Na, K, Mg, Ca, Si, Al, V, Mn, Fe, and Co) and anions (Cl(-) and SO(4)(2-)). Box plots of the data acquired were used to evaluate the reproducibility achieved at different experimental conditions. Both the amount of sample (A) and leaching time (B) had a significant effect on the element stripping whereas the L/S ratio influenced only few elements. The lowest dispersion values have been observed when 1.0 g was leached with an L/S ratio equal to 10, shaking during 4 h. The entire method is completed within few hours, and it is simple, feasible and reliable in laboratory conditions.


Circulating interferon-γ-inducible Cys-X-Cys chemokine receptor 3 ligands are elevated in humans with aortic aneurysms and Cys-X-Cys chemokine receptor 3 is necessary for aneurysm formation in mice.
Inflammation is associated with the formation of aortic aneurysm. This study investigates the role of inducible Cys-X-Cys chemokine receptor 3 and its ligands in the pathogenesis of arterial aneurysms. Plasma samples from patients with or without a diagnosis of thoracic aortic aneurysms were analyzed by enzyme-linked immunosorbent assay for the T-helper 1 cytokine interferon-γ and the interferon-γ-inducible chemokine receptor 3 ligands: interferon-inducible protein-10, interferon-inducible T-cell alpha chemoattractant, and monokine induced by interferon gamma. Patient charts were reviewed for demographics, initial aortic diameter, and growth rates. Aneurysm diameter and growth rates were correlated with plasma cytokine and chemokine levels using linear regression analysis. We used an animal model of aneurysm formation, where calcium chloride is applied topically to the carotid arteries of wild-type and Cys-X-Cys chemokine receptor 3(-/-) mice. After 10 weeks, the arteries were harvested and analyzed by histology and immunohistochemistry. Patients with thoracic aortic aneurysms had significant elevations in circulating interferon-γ, interferon-inducible protein-10, interferon-inducible T-cell alpha chemoattractant, and monokine induced by interferon gamma compared with referent patients (P < .001). Cytokine and chemokine plasma levels did not correlate with aneurysm size or growth rates. Cys-X-Cys chemokine receptor 3(-/-) mice were protected from aneurysm formation and showed decreased vascular infiltration by CD45(+) leukocytes. Elevated plasma levels of interferon-γ and Cys-X-Cys chemokine receptor 3-binding chemokines are present in patients with thoracic aortic aneurysms. The Cys-X-Cys chemokine receptor 3 receptor is necessary for vascular inflammation and the formation of arterial aneurysms in mice.


Derivatives of (R,S)-1-N-(theophyllinyl-7'-ethyl)-amino-2-propanol with antiarrhythmic activity.
Three (R,S)-1-N-(theophyllinyl-7'-ethyl)-amino-2-propanol derivatives were obtained as soluble hydrochlorides and tested in four models of experimental arrhythmia. Two compounds 1a and 2 have shown antiarrhythmic properties and very low toxicity.


Hospital dietetics and food service in developing countries: I. The Middle East.
A survey of hospital food service and dietetics was conducted in the largest hospitals of six Middle Eastern countries: Bahrain, Jordan, Kuwait, Lebanon, Saudi Arabia, and Syria. There were very few individuals with training in food service and dietetics in any of the countries. The effect of this lack of training on hospital food service and dietetics is discussed. Recommendations are made that would result in improvements in hospital food service and dietetics in the Middle East.


Integrating health, psychosocial and legal support for pregnant women in South Africa.
Can combining HIV testing with legal support help pregnant women disclose their HIV status safely to their partners? Suzanne Maman and her colleagues describe the South Africa HIV Antenatal Care Post-Test Support Study (SAHAPS), a unique intervention to include legal education and referral with a package of post-test support services in KwaZulu-Natal, South Africa.


KCa1.1 channels contribute to optogenetically driven post-stimulation silencing in cerebellar molecular layer interneurons.
Using cell-attached recordings from molecular layer interneurons (MLI) of the cerebellar cortex of adult mice expressing channel rhodopsin 2, we show that wide-field optical activation induces an increase in firing rate during illumination and a firing pause when the illumination ends (post-stimulation silencing; PSS). Significant spike rate changes with respect to basal firing rate were observed for optical activations lasting 200 ms and 1 s as well as for 1 s long trains of 10 ms pulses at 50 Hz. For all conditions, the net effect of optical activation on the integrated spike rate is significantly reduced because of PSS. Three lines of evidence indicate that this PSS is due to intrinsic factors. Firstly, PSS is induced when the optical stimulation is restricted to a single MLI using a 405-nm laser delivering a diffraction-limited spot at the focal plane. Secondly, PSS is not affected by block of GABA-A or GABA-B receptors, ruling out synaptic interactions amongst MLIs. Thirdly, PSS is mimicked in whole-cell recording experiments by step depolarizations under current clamp. Activation of Ca-dependent K channels during the spike trains appears as a likely candidate to underlie PSS. Using immunocytochemistry, we find that one such channel type, KCa1.1, is present in the somato-dendritic and axonal compartments of MLIs. In cell-attached recordings, charybdotoxin and iberiotoxin significantly reduce the optically induced PSS, while TRAM-34 does not affect it, suggesting that KCa1.1 channels, but not KCa3.1 channels, contribute to PSS.


Psychiatric illness in male doctors and controls: an analysis of Scottish hospitals in-patient data.
An investigation was undertaken into the first admissions to (for the years 1963, 1965, 1968, 1972) and the total discharges from (for the years 1963-72) Scottish mental hospitals and psychiatric units of male doctors and other social class I males. The overall rates for both first admission and for all discharges were more than twice as high among male doctors as among other social class I males. First admission and total discharge rates for drug dependence, alcoholism, neurotic and 'functional' depression and for affective psychosis were all significantly higher among doctors than non-doctors. Doctors were more likely than non-doctors to have been referred by themselves or by medical sources other than general practitioners, and were as willing as non-doctors to enter hospital voluntarily. Creater access to psychiatrists may have contributed to their higher rates in in-patient care, but it is improbable that such factors accounted for all of the excess in rates of drug dependence, alcoholism and depression.


The Role of Frozen-Section in the Surgical Management of Patients with Endometrial Intraepithelial Neoplasia.
Patients with endometrial intraepithelial neoplasia may have concurrent endometrial cancer if managed surgically or develop cancer in time if managed conservatively. Therefore, intraoperative assessment of the uterus may be helpful if a surgical approach is decided on. Our study aimed to investigate the role of frozen-section examination in patients with endometrial intraepithelial neoplasia. Patients with endometrial intraepithelial neoplasia who were subjected to hysterectomy with intraoperative frozen-section assessment were included. Main outcome measures were the rates of concurrent endometrial cancer and concurrent high-risk endometrial cancer as well as the efficacy of frozen-section in the detection of concurrent invasive disease and in the designation of low-risk and high-risk features. The study group consisted of seventy-three patients. Permanent pathology revealed endometrial adenocarcinoma in 19.2% whereas only one patient (1.4%) had high-risk disease necessitating surgical staging. Frozen-section diagnoses were consistent with final pathology in 93.2% of patients in terms of the presence or absence of co-existent carcinoma. When frozen-section reports were further evaluated in terms of the presence or absence of high-risk endometrial carcinoma, consistency with the final pathology was seen in 98.6% of patients. Co-existent endometrial cancer is not uncommon in endometrial intraepithelial neoplasia. Intraoperative frozen-section evaluation should therefore be considered whenever possible. Frozen-section is effective in the detection of coexistent invasive disease and in the designation of low-risk features. Although coexistent high-risk cancer is extremely rare, frozen-section assessment is not successful in determining high-risk features. Therefore, a re-staging surgery may be required on rare occasions.


Bilateral Wilms' tumors: a single-center experience with 19 cases.
Bilateral Wilms' tumors present a therapeutic challenge, particularly with delay in presentation, when there is poor response to chemotherapy and when associated with nephroblastomatosis. The primary aim of management is eradication of neoplasm, while at the same time preserving of renal function. Nineteen bilateral Wilms' tumors were seen in our service between 1981 and 2003. This represented 10% of the 190 patients with Wilms' tumors seen during this period. There were 12 female and 7 male patients ranging in age from 7 months to 8 years. Fourteen had synchronous presentation, one of whom had liver metastasis at diagnosis. Of the 5 patients with metachronous tumors, 3 had their initial nephrectomies done elsewhere. Nephroblastomatosis was identified in 18 (95%) of the patients. Treatment was, in most cases, according to National Wilms Tumor Study Group protocols, with initial bilateral biopsy, neoadjuvant chemotherapy, and tumorectomy. Where indicated, nephrectomy (partial or complete) involved using ice dam topical cooling and vascular control, and in one case, bench surgery and extensive renal reconstruction with orthotopic autotransplantation. Revision tumorectomy was used on 3 occasions for recurrence in areas of nephroblastomatosis. There were 6 extrarenal relapses. Ten patients are alive and free of disease 1 to 15 years after treatment, all with well preserved renal function (lowest recorded glomerular filtration rate was 85 mL/min per 1.73 m2). Nine have died (2 of unrelated disease), including 6 of the 7 with spread outside the kidney. All 3 with unfavorable histology are alive. Of the 5 with metachronous presentations, 4 are alive, as are 7 of 10 who presented in the last decade. Appropriate chemotherapy and conservative nephron-sparing and innovative surgery can achieve good results with preservation of adequate renal function in nearly all cases. Nephroblastomatosis was an almost universal finding and requires close monitoring because Wilms' tumors developed in residual suspect areas. Revision surgery was effective. Unfavorable histology did not have a reduced survival in our series. Metastatic spread outside the kidney had a poor prognosis.


[The principle of spirituality in healthcare establishments, the role of healthcare supervisors].
Healthcare teams are sometimes questioned by patients and their loved ones concerning respect for their desires or performing rites, whether religious or part of their own personal beliefs. While caregivers are convinced that it is part of their job to meet these needs, this is sometimes contrary to the requirements of neutrality and laïcité--the French concept of secularity--on healthcare premises. Nonetheless, each can contribute to the evolution of the general reflections undertaken by a team or an organization.


Unfractionated heparin and low molecular weight heparin do not inhibit the growth of proliferating human arterial smooth muscle cells in culture.
To clarify the effects of unfractionated heparin (UH) and low molecular weight heparin (LMWH) on proliferating human smooth muscle cells (SMC) compared to growth arrested SMC. A cell culture study where proliferating SMC were exposed to different concentrations of UH and LMWH and the effect on proliferation and collagen secretion was studied. Growth arrested SMC were stimulated with serum and the effect of UH on proliferation was measured. Sections of Medical Angiology and Vascular Surgery, Malmö General Hospital, Sweden. Human SMC were established from arterial tissue obtained at vascular surgery or at organ donation. Effects of UH and LMWH on total cellular DNA, 3H-thymidine incorporation and collagen secretion using proliferating and growth arrested human SMC in culture. In proliferating SMC that had not been growth arrested, 1 and 10 IU/ml UH and LMWH significantly increased total cellular DNA compared to controls while DNA synthesis was not influenced. The higher cellular DNA was probably not a consequence of increased proliferation as DNA synthesis was not affected by UH or LMWH. The increased total cellular DNA could instead be due to reduced cell death. Higher concentrations (10 IU/ml) of UH and LMWH also increased collagen secretion. In control experiments with UH DNA, synthesis was decreased in stimulated human SMC that had been growth arrested previously to heparin exposure. The effects of UH and LMWH on SMC proliferation will depend on the proliferative state of the SMC. The results might be of relevance for the understanding of the atherosclerotic process and for pharmacologic interventions to prevent restenosis after angioplasty or surgery.


Effectiveness of the European Natura 2000 network to sustain a specialist wintering waterbird population in the face of climate change.
Analysis of coordinated Greater Scaup (Aythya marila) count data from the last 30 years showed a 38.1% decrease in wintering numbers in North-West Europe, from 309,000 during 1988-1991 to c.192,300 individuals during 2015-2018. Annual trends in wintering numbers differed throughout the range. Numbers decreased in the UK, Ireland, and in the Netherlands, while numbers were stable in Denmark. Germany, Poland, Sweden, and Estonia showed increasing numbers, suggesting a shift in the distribution of the species within its wintering grounds towards the east and north. Higher temperatures in northern and eastern areas were correlated with the range shift of the wintering distribution. Deaths from bycatch drowning of Scaup in fishing gear have significantly decreased in recent decades in the Netherlands, where currently the greatest threat is considered the deterioration of food resources. The increasing concentration of wintering Scaup in coastal Poland and Germany (where lack of effective implementation of conservation measures fail to protect the species from the impacts of bycatch and declining food quality) pose major threats to the entire population.


Inhibitory effect of LY 255283 on the synthesis of leukotriene B(4) and thromboxane A(2) in human peripheral blood polymorphonuclear leukocytes and monocytes.
LY 255283 [(1-(5-ethyl-2-hydroxy-4-(6-methyl-6-)1H-tetrazol-5-yl)-heptyloxy) phenyl)ethanone], a specific leukotriene B(4) (LTB(4)) receptor antagonist, inhibited the production of LTB(4) in human peripheral blood polymorphonuclear leukocytes (PMNL) and in monocytes activated by calcium ionophore A23187. In human monocytes activated by ionophore it inhibited also the production of thromboxane B(2) (TXB(2)). The effect of LY 255283 on 5-lipoxygenase (5-LO) and LTA(4) hydrolase activities which catalyse the production of LTB(4) and LTA(4) has not been studied yet. It is thought that LY 255283 may inhibit the production of LTB(4) and TXA(2) by antagonising the effect of ionophore-induced LTB(4) on 5-lipoxygenase and cyclooxygenase in human peripheral blood PMNL and monocytes.


Inhibitory effects of group II mGluR-related drugs on memory performance in mice.
The cAMP/protein kinase A signaling pathway is negatively modulated by group II metabotropic glutamate receptors (mGluRs), and the cross-talk that occurs between these receptors may modulate learning and memory. To examine the relationship among cAMP/PKA-signaling pathway activity, group II mGluRs, and learning and memory, mice were trained to perform a step-through-type passive avoidance task, and 10 min before each avoidance trial the following drugs were injected intracisternally (i.cist.): vehicle (0.05% dimethylsulfoxide); a specific group II mGluR agonist, DCG-IV (1-50 ng/mouse); a specific group II mGluR antagonist, LY341495 (10-300 ng); a selective inhibitor of cAMP-specific phosphodiesterase, rolipram (100-1000 ng); an activator of adenylyl cyclase, forskolin (25-250 ng); a specific inhibitor of PKA, H-89 (150 or 300 ng) or; an activator of protein kinase C, phorbol 12-myristate 13-acetate (PMA 200 ng). DCG-IV (25 and 50 ng) or LY341495 (150 and 300 ng) reduced the latency in the avoidance task. The reduction of latency by DCG-IV was not observed in mice coinjected with DCG-IV (50 ng) together with rolipram (500 ng) or forskolin (25 ng). Conversely, coinjection of LY341495 with 100 or 1000 ng rolipram, or with 25 or 250 ng forskolin tended to potentiate the LY341495-induced shortening of latency. In addition, the reduction of latency by DCG-IV (50 ng) was not observed in mice coinjected with DCG-IV and PMA together. However, the reduction of latency by LY341495 (300 ng) was potentiated when the drug was coadministered with PMA. These results suggest that changes in the cAMP/PKA-signaling pathway, mediated by group II mGluRs, influence memory in the passive avoidance task, and that both the excessive activation and deactivation of this pathway may induce the impairment of learning and memory.


Use of glucose as reductant to recover Co from spent lithium ions batteries.
A hydrometallurgical leaching process has been developed for recovery of Co and Li from cathode material (LiCoO2) collected from spent LIBs using a mix solution of glucose and phosphoric acid. The spent LiCoO2 before and after leaching process are analyzed by scanning electron microscopy. A leaching rate of about 98% Co and nearly 100% Li is presented with 1.5mol/L phosphoric acid and 0.02mol/L glucose at 80°C in about 2h. During leaching process, glucose was oxidized into monocarboxylic acid with reduction of Co(III) to Co(II). Co in solution was recovered as Co-oxalate after leaching process. Using glucose as reductant to dissolve LiCoO2 with chelating agent of phosphoric acid is achieved here.


[Effect of C21 steroidal glycoside from root of Cynanchum auriculatum on D-galactose induced aging model mice].
To study the effect of C21 steroidal glycoside (CSG) from the root of Cynanchum auriculatum from Jiangsu on D-galactose (D-gal) induced aging model mice. D-gal aging mouse model was established by cervicodorsal region subcutaneous injection with D-gal once a day for eight successive weeks. The mice in the normal control group (NCG, non-modeled) and the model control group (MCG, modeled but untreated) were treated with 1% CMC-Na. The model mice in the low, middle and high-dose CSG and Vitamin E treated groups were treated with a dose of (10, 20, 40, 100 mg x kg(-1) per day, respectively. The SOD activity, MDA content and telomerase activity in serum, heart, liver and brain tissues of mice were measured. CSG could obviously increase the SOD activity and decrease the MDA level in serum, heart, liver and brain tissues in D-gal aging mice (P < 0.01). There was no significant difference between three CSG treated groups and Vitamin E treated groups. In comparison of telomerase activity between MCG and the treated groups, it was shown that there was a significant increase in serum in middle and high dose group, and in heart tissues in CSG and Vit E treated groups, but was not in liver and brain tissue. This study demonstrates that CSG can antagonize free radical injury, increase the SOD activity and decrease the MDA content of serum, heart, liver and brain in D-gal aging mice, and increase the telomerase activity in serum and heart tissues but not in liver and brain tissue.


The Diagnostic Accuracy of Ultrasonography for the Diagnosis of Rib Fractures in Patients Presenting to Emergency Department With Blunt Chest Trauma.
Rib fractures are the most common complications of blunt chest trauma (BCT). Computed tomography (CT) is the modality of choice for BCT, but with several disadvantages. Ultrasonography (US) is an inexpensive, readily available, and relatively harmless imaging alternative. However, a direct comparison of the sonographic evaluation of the rib as a whole with CT as a reference has not been performed to date. This study aimed to compare the diagnostic accuracy of US with CT for the detection of rib fractures in patients who presented to emergency department (ED) with BCT. We included a convenience sample of adult patients who presented to the ED with thoracic pain after BCT in the last 24 h in this prospective, observational, diagnostic accuracy study. The diagnostic utility of US performed by an emergency physician was compared with thorax CT. The final study population included 145 patients. The diagnostic accuracy of US was 80% with a sensitivity of 91.2% and specificity of 72.7% for the detection of any rib fracture (positive likelihood ratio 3.4 and negative likelihood ratio 0.12). If we considered each rib separately, the sensitivity of US decreased to 76.7% and specificity increased to 82.7% (81.3% accuracy). A negative US of the site of the highest tenderness and neighboring ribs in a patient with BCT who presented to the ED with lateralizing pain decreases the possibility of a rib fracture significantly. However, a positive US performs poorly to specify the exact location and number of the fractured ribs.


Strategies for Maintaining Brain Health: The Role of Stroke Risk Factors Unique to Elderly Women.
Stroke risk and prevalence increase with advanced age and women tend to be older than men at the time of their first stroke. Advanced age in women confers unique stroke risks that are beyond reproductive factors. Previous reviews and guidelines have largely focused on risk factors specific to women, with a predominant focus on reproductive factors and, therefore, younger to middle-aged women. This review aims to specifically describe stroke risk factors in elderly women, the population of women where the majority of strokes occur, with a focus on atrial fibrillation, hormone therapy, psychosocial risk factors, and cognitive impairment. Our review suggests that prevention and management of stroke risks that are unique or more prevalent in elderly women needs a coordinated system of care from general physicians, general neurologists, vascular and cognitive neurologists, psychologists, cardiologists, patients, and their caretakers. Early identification and management of the elderly woman-specific and traditional stroke risk factors is key for decreasing stroke burden in elderly women. Increased education among elderly women regarding stroke risk factors and their identification should be considered, and an update to the guidelines for prevention of stroke in women is strongly encouraged.


Prostaglandins.
A discussion of important aspects of the effects of prostaglandins on arteries must include (a) the nature of the receptors for the different humoral agents, (b) the potential modulatory role that endogenously produced prostaglandins may play when other vasoactive hormones are present, and (c) the potential for cell-to-cell transfer of substrates for formation of novel biologically active arachidonic acid metabolites. Evidence suggests that at least two vasodilator receptors for prostaglandins exist (PGE2 and PGI2) and at least one vasoconstrictor receptor (TXA2), probably more. Activation of vasodilator mechanisms by endogenously produced vasodilator prostaglandins in isolated arteries or in vivo can attenuate the vasoconstrictor activity of angiotensin II and in some cases mediate the vasodilator effects of bradykinin. Perhaps the most important source of vasoactive arachidonic acid metabolites may be the interaction of blood cells with the vessel wall. Platelets produce thromboxane (TXA2), which has vasoconstrictor effects at 10(-8) M in vitro. Diversion of the precursor from the platelet by selective inhibition of thromboxane synthetase can provide substrate for vascular PGI2 synthesis. Other interactions between leukocytes, platelets, endothelium cells, and smooth-muscle cells are likely to reveal further pathways for the formation of vasoactive arachidonic acid metabolites.


Retinal damage by light: possible implication of singlet oxygen.
A new hypothesis is proposed in an attempt to explain the mechanism of the irreversible damage which can be induced in the retina by visible light. Upon illumination, retinal generates singlet oxygen and this reactive species can produce lipid peroxidation which in turn may induce membrane instability.


Sensitivity of individual-donation and minipool nucleic acid amplification test options in detecting window period and occult hepatitis B virus infections.
Several comparison studies showed that the Ultrio assay (Novartis Diagnostics) used in individual-donation nucleic acid amplification testing (ID-NAT) format was as sensitive as the TaqScreen assay (Roche) on minipools of six donations (MP6), but the sensitivity of HBV DNA detection has been improved in the new Ultrio Plus version of the assay. A head-to-head comparison study was designed to compare the clinical sensitivity of the Ultrio and Ultrio Plus assay in ID, MP4, and MP8 formats using TaqScreen MP6 as a reference assay. Plasma samples of 107 hepatitis B surface antigen (HBsAg)-negative, HBV ID-NAT (Ultrio) positive-yield samples and 29 HBV DNA-negative, HBsAg-positive samples were used for comparison of NAT options in replicate testing of dilutions. Viral loads and relative sensitivities were determined by probit analysis against the Eurohep standard. Ultrio Plus detected a significantly (p < 0.00001) higher proportion of replicate assays on HBV NAT yields (77%) than Ultrio ID (62%) and TaqScreen MP6 (47%), whereas Ultrio Plus MP4 and MP8 detected 53 and 41%, respectively. On HBsAg-yield samples missed by Ultrio screening, the reactivity rate increased significantly (p < 0.0001) from 23% in Ultrio to 65% in Ultrio Plus and further to 72% (p = 0.10) in the TaqScreen assay. The overall improvement factor of the analytical sensitivity offered by the target enhancer reagent in the Ultrio Plus assay was 2.5 (2.0-3.1)-fold on the Ultrio yield samples, but 43 (11-350)-fold on the HBsAg yields. In ID-NAT format the analytical sensitivity of TaqScreen relative to Ultrio Plus was 2.0 (1.0-4.2), 0.9 (0.7-1.3), and 1.6 (0.9-3.0) on the Eurohep standard, HBV NAT-, and HBsAg-yield samples respectively. The clinical sensitivity of the currently available commercial NAT methods is mainly driven by the pool size.


The use of a genetically engineered herpes simplex virus (R7020) with ionizing radiation for experimental hepatoma.
The herpes simplex virus (HSV) recombinant virus R7020 is an attenuated virus designed as a candidate for immunization against both HSV-1 and HSV-2 infections. It was extensively tested in an experimental animal system and in a healthy human adult population without significant untoward effects. We report on the use of R7020 with ionizing radiation as an oncolytic agent for hepatomas. Two hepatoma cell lines were studied, Hep3B and Huh7. R7020 replicated to higher titers in Hep3B cells than in Huh7 cells. Tissue culture studies correlated with hepatoma xenograft responses to R7020. R7020 was more effective in mediating Hep3B tumor xenograft regression compared with Huh7. Ionizing radiation combined with R7020 also showed differential results in antitumor efficacy between the two cell lines in tumor xenografts. Ionizing radiation enhanced the replication of R7020 in Hep3B xenografts. Moreover, the combination of ionizing radiation and virus caused a greater regression of xenograft volume than either R7020 or radiation alone. Ionizing radiation had no effect on the replication of R7020 virus in Huh7 xenografts. These results indicate that a regimen involving infection with an appropriate herpesvirus such as R7020 in combination with ionizing radiation can be highly effective in eradicating certain tumor xenografts.


Effect of Disinfectants with Different Active Ingredients on Biofilm Formation in Pseudomonas aeruginosa.
We compared the effects of disinfectants on biofilms of 10 Pseudomonas aeruginosa strains isolated from different loci of patients with purulent-septic infections. Identification was carried out by standard bacteriological methods. To substantiate the prospects of using in hospitals and to assess the effect of disinfectants on P. aeruginosa biofilms, the following disinfectants were used in various concentrations: Sekusept Aktiv, A-DEZ, and Monitor Oxy. All clinical strains of P. aeruginosa showed the ability to form biofilms. Both oxygen-containing and quaternary ammonium compounds effectively inhibited the formation of biofilms. In more than 50% cases, disinfectants with different active ingredients did not destroy pre-formed of P. aeruginosa biofilms.


Multiple cellular origins and molecular evolution of intrahepatic cholangiocarcinoma.
Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy associated with unfavorable prognosis and for which no effective treatments are available. Its molecular pathogenesis is poorly understood. Genome-wide sequencing and high-throughput technologies have provided critical insights into the molecular basis of ICC while sparking a heated debate on the cellular origin. Cancer exhibits variabilities in origin, progression and cell biology. Recent evidence suggests that ICC has multiple cellular origins, including differentiated hepatocytes; intrahepatic biliary epithelial cells (IBECs)/cholangiocytes; pluripotent stem cells, such as hepatic stem/progenitor cells (HPCs) and biliary tree stem/progenitor cells (BTSCs); and peribiliary gland (PBG). However, both somatic mutagenesis and epigenomic features are highly cell type-specific. Multiple cellular origins may have profoundly different genomic landscapes and key signaling pathways, driving phenotypic variation and thereby posing significant challenges to personalized medicine in terms of achieving the optimal drug response and patient outcome. Considering this information, we have summarized the latest experimental evidence and relevant literature to provide an up-to-date view of the cellular origin of ICC, which will contribute to establishment of a hierarchical model of carcinogenesis and allow for improvement of the anatomical-based classification of ICC. These new insights have important implications for both the diagnosis and treatment of ICC patients.


Heightened sensitivity to high-calorie foods in children at risk for obesity: insights from behavior, neuroimaging, and genetics.
Pediatric obesity is a major public health concern. Genetic susceptibility and increased availability of energy-dense food are known risk factors for obesity. However, the extent to which these factors jointly bias behavior and neural circuitry towards increased adiposity in children remains unclear. While undergoing fMRI, 108 children (ages 5-11y) performed a food-specific go/no-go task. Participants were instructed to either respond ("go") or inhibit responding ("no-go") to images of food or toys. Half of the runs depicted high-calorie foods (e.g., pizza) whereas the other half depicted low-calorie foods (e.g., salad). Children were also genotyped for a DNA polymorphism associated with energy intake and obesity (FTO rs9939609) to examine the influence of obesity risk on behavioral and brain responses to food. Participants demonstrated differences in behavioral sensitivity to high- and low-calorie food images depending on task demands. Participants were slower but more accurate at detecting high- (relative to low-) calorie foods when responding to a neutral stimulus (i.e., toys) and worse at detecting toys when responding to high-calorie foods. Inhibition failures were accompanied by salience network activity (anterior insula, dorsal anterior cingulate cortex), which was driven by false alarms to food images. Children at a greater genetic risk for obesity (dose-dependent model of the FTO genotype) demonstrated pronounced brain and behavioral relationships such that genetic risk was associated with heightened sensitivity to high-calorie food images and increased anterior insula activity. These findings suggest that high-calorie foods may be particularly salient to children at risk for developing eating habits that promote obesity.


Radical prostatectomy after previous transurethral resection of the prostate: oncological, surgical and functional outcomes-a meta-analysis.
The current study aimed to carry out a comprehensive meta-analysis on the existing evidence to quantify and compare the oncological, surgical and functional outcomes following radical prostatectomy between TURP group and Non-TURP group. A systematic literature search was conducted using EMBASE, PubMed and Cochrane databases to identify relevant studies published in English up to March 2019. A meta-analysis was conducted using Review Manager. There were 13 studies included in the present study. Our results suggest that TURP group demonstrates a significantly higher positive surgical margin rate, bladder neck reconstruction rate and overall complication rate compared with Non-TURP group (OR = 1.31, 95% CI 1.09-1.58, P = 0.004, I2 = 0%; OR = 14.36, 95% CI 2.93-70.45, P = 0.001, I2 = 81%; OR = 2.63, 95% CI 1.87-3.71, P < 0.00001, I2 = 0%); whereas TURP group demonstrates a significantly lower nerve sparing rate compared with Non-TURP group (OR = 0.30, 95% CI 0.22-0.43, P < 0.00001, I2 = 40%); the operation time, blood loss and 1-year urinary continence rate are same between TURP group and Non-TURP group (MD = 4.25, 95% CI - 0.13 to 8.63, P = 0.06, I2 = 34%; MD = 27.29, 95% CI - 10.31 to 64.90, P = 0.15, I2 = 39%; OR = 0.68, 95% CI 0.43-1.06, P = 0.09, I2 = 0%). This meta-analysis demonstrates that Non-TURP group may have a great advantage over TURP group in terms of positive surgical margin rate, bladder neck reconstruction rate, overall complication rate and sparing rate. The operation time, blood loss and 1-year urinary continence rate are comparable between TURP group and Non-TURP group. Therefore, important information should be given to those patients at risk of prostate cancer that TURP procedure may increase perioperative complications in case of a following radical prostatectomy. In the meantime, our meta-analysis found that each of these four subgroups (RARP, LRP, ORP and RARP/ORP) has its own advantages or disadvantages in every pool results. So when radical prostatectomy is performed on patients with TURP history, the appropriate operation method should be selected as per the conditions of patients, doctors and hospitals.


Vesicles from docosahexaenoic acid.
In dilute aqueous solution and at room temperature, cis-4,7,10,13,16,19-docosahexaenoic acid (DHA) self-assembles into vesicles (self-closed bilayers), if the molar ratio of the neutral form of DHA to anionic DHA is kept between 1:1 and 1:3 (corresponding to a bulk pH between 8.5 and 9.2 for a system with 10 mM DHA). By using polycarbonate membrane extrusion, stable unilamellar DHA vesicles with an average diameter of 80 nm can be prepared at pH 8.8. Cryo-transmission electron microscopy indicates that the width of the DHA bilayers in the vesicles is clearly below twice the length of an extended DHA molecule, indicating a high conformational flexibility of DHA within the vesicle bilayer. These DHA bilayers have a similar thickness like bilayers of vesicles prepared at pH 8.5 from oleic acid (cis-9-octadecenoic acid). Using calcein as fluorescent reference compound, it is shown that water-soluble molecules can be encapsulated inside DHA vesicles which may make them interesting for medical or food applications.


Preventive effects of an immunostimulating product on recurrent infections of chronic bronchitis in the elderly.
The effect of an immunostimulating drug, OM-85 BV, was demonstrated on recurrent infection rates in 265 elderly patients with a defined state of chronic bronchitis, during a 6-month, double-blind, placebo-controlled trial. Patients receiving OM-85 BV presented less infections (p = 0.005) and a significantly reduced intake of antibiotics (p = 0.02) as compared to those receiving a placebo and the antibiotic intake was significantly reduced (p = 0.02).


Poly (A)-specific ribonuclease deficiency impacts oogenesis in zebrafish.
Poly (A)-specific ribonuclease (PARN) is the most important 3'-5'exonuclease involved in the process of deadenylation, the removal of poly (A) tails of mRNAs. Although PARN is primarily known for its role in mRNA stability, recent studies suggest several other functions of PARN including a role in telomere biology, non-coding RNA maturation, trimming of miRNAs, ribosome biogenesis and TP53 function. Moreover, PARN expression is de-regulated in many cancers, including solid tumours and hematopoietic malignancies. To better understand the in vivo role of PARN, we used a zebrafish model to study the physiological consequences of Parn loss-of-function. Exon 19 of the gene, which partially codes for the RNA binding domain of the protein, was targeted for CRISPR-Cas9-directed genome editing. Contrary to the expectations, no developmental defects were observed in the zebrafish with a parn nonsense mutation. Intriguingly, the parn null mutants were viable and fertile, but turned out to only develop into males. Histological analysis of the gonads in the mutants and their wild type siblings revealed a defective maturation of gonadal cells in the parn null mutants. The results of this study highlight yet another emerging function of Parn, i.e., its role in oogenesis.


Highly effective copper-catalyzed decarboxylative coupling of aryl halides with alkynyl carboxylic acids.
We have developed a highly effective copper-catalyzed decarboxylative coupling of alkynylcarboxylic acids with various aryl and alkyl halides at 2 mol% loading of copper. This method is simple, economical and practical for the synthesis of disubstituted alkyne compounds.


Combined angioplasty and pharmacological intervention versus thrombolysis alone in acute myocardial infarction (CAPITAL AMI study).
We compared a strategy of tenecteplase (TNK)-facilitated angioplasty with one of TNK alone in patients presenting with high-risk ST-segment elevation myocardial infarction (STEMI). Previous trials show that thrombolysis followed by immediate angioplasty for the treatment of STEMI does not improve ischemic outcomes compared with thrombolysis alone and is associated with excessive bleeding complications. Since the publication of these trials, however, significant pharmacological and technological advances have occurred. We randomized 170 patients with high-risk STEMI to treatment with TNK alone (84 patients) or TNK-facilitated angioplasty (86 patients). The primary end point was a composite of death, reinfarction, recurrent unstable ischemia, or stroke at six months. At six months, the incidence of the primary end point was 24.4% in the TNK-alone group versus 11.6% in the TNK-facilitated angioplasty group (p = 0.04). This difference was driven by a reduction in the rate of recurrent unstable ischemia (20.7% vs. 8.1%, p = 0.03). There was a trend toward a lower reinfarction rate with TNK-facilitated angioplasty (14.6% vs. 5.8%, p = 0.07). No significant differences were observed in the rates of death or stroke. Major bleeding was observed in 7.1% of the TNK-alone group and in 8.1% of the TNK-facilitated angioplasty group (p = 1.00). In patients presenting with high-risk STEMI, TNK plus immediate angioplasty reduced the risk of recurrent ischemic events compared with TNK alone and was not associated with an increase in major bleeding complications.


Genetic architecture of band neutrophil fraction in Iceland.
The characteristic lobulated nuclear morphology of granulocytes is partially determined by composition of nuclear envelope proteins. Abnormal nuclear morphology is primarily observed as an increased number of hypolobulated immature neutrophils, called band cells, during infection or in rare envelopathies like Pelger-Huët anomaly. To search for sequence variants affecting nuclear morphology of granulocytes, we performed a genome-wide association study using band neutrophil fraction from 88,101 Icelanders. We describe 13 sequence variants affecting band neutrophil fraction at nine loci. Five of the variants are at the Lamin B receptor (LBR) locus, encoding an inner nuclear membrane protein. Mutations in LBR are linked to Pelger-Huët anomaly. In addition, we identify cosegregation of a rare stop-gain sequence variant in LBR and Pelger Huët anomaly in an Icelandic eight generation pedigree, initially reported in 1963. Two of the other loci include genes which, like LBR, play a role in the nuclear membrane function and integrity. These GWAS results highlight the role proteins of the inner nuclear membrane have as important for neutrophil nuclear morphology.


Correction to: Epigenetic priming sensitizes gastric cancer cells to irinotecan and cisplatin by restoring multiple pathways.
Recently published the priming.


Novel HIV-1 RNA biogenesis inhibitors identified by virtual pharmacophore-based screening.
The complex between the Rev protein of HIV-1 and the Rev Recognition Element (RRE) within the virus RNA promotes nuclear export of unspliced or incompletely spliced viral transcripts and is required for virus transmission. Here, we have screened a virtual collection of compounds using a pharmacophore based on the chemical similarity of previously characterized inhibitors to identify new chemical scaffolds blocking the RRE-Rev interaction. The best molecules discovered with this strategy inhibited the complex by binding to the RRE and exhibited substantial antiretroviral activity (between 0.582 and 11.3 μM EC50 values) likely associated to inhibitory actions on viral transcription and Rev function. These results have allowed us to identify structural features required for RRE-Rev inhibition as well as to add new compounds to the pool of possible candidates for developing antiretroviral agents based on blockage of HIV-1 RNA biogenesis.


A new approach to the difficult assessment of aldosterone secretion in anephric patients.
A new method for the assessment of endogenous formation of aldosterone in anephric patients is described. (1, 2-3H) aldosterone was administered i.v. to patients 1-2 days before hemodialysis, and then the specific activity (SA) of tetrahydroaldosterone glucosiduronate, the major aldosterone metabolite, was measured in the dialysate using a specific radioimmunoassay. The aldosterone secretion rate was determined from the extent of isotope dilution by endogenous metabolite. Aldosterone secretion rates measured in 10 patients were for the most part low. The secretion rate determined in blood from the aldosterone metabolic clearance rate and plasma aldosterone concentration closely approximate secretion rate values obtained by the isotope dilution method in 3 of 4 patients. In 2 patients in whom ACTH was administered chronically, radio-labeled aldosterone was administered at the start of the study and then the day to day aldosterone secretory response to ACTH was determined from the SA of tetrahydroaldosterone in blood. Aldosterone secretion continuously increased for as long as ACTH was administered.


Six-Month Impairment in Cognition, Mental Health, and Physical Function Following COVID-19-Associated Respiratory Failure.
To determine the prevalence and extent of impairments impacting health-related quality of life among survivors of COVID-19 who required mechanical ventilation, 6 months after hospital discharge. Multicenter, prospective cohort study, enrolling adults 18 years old or older with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection who received mechanical ventilation for 48 hours or more and survived to hospital discharge. Eligible patients were contacted 6 months after discharge for telephone-based interviews from March 2020 to December 2020. Assessments included: Montreal Cognitive Assessment-Blind, Hospital Anxiety and Depression Scale, Impact of Event Scale-6, EuroQOL 5 domain quality-of-life questionnaire, and components of the Multidimensional Dyspnea Profile. Two tertiary academic health systems. Of 173 eligible survivors, a random sample of 63 were contacted and 60 consented and completed interviews. None. Mean age was 57 + 13 years and mean duration of invasive mechanical ventilation was 14 + 8.2 days. Six months post-discharge, 48 patients (80%; 95% CI, 68-88%) met criteria for post-intensive care syndrome (PICS), with one or more domains impaired. Among patients with PICS, 28 (47%; 95% CI, 35-59%) were impaired in at least 2 domains, and 12 (20%; 95% CI, 12-32%) impaired in all three domains. Significant symptoms of post-traumatic stress were present in 20 patients (33%; 95% CI, 23-46%), anxiety in 23 (38%; 95% CI, 27-51%), and depression in 25 (42%; 95% CI, 30-54%). Thirty-three patients (55%; 95% CI, 42-67%) had impairments in physical activity; 25 patients (42%; 95% CI, 30-54%) demonstrated cognitive impairment. Eighty percent of COVID-19 survivors who required mechanical ventilation demonstrated PICS 6 months after hospital discharge. Patients were commonly impaired in multiple PICS domains as well as coexisting mental health domains.


Comparison of the analgesic efficacy of flurbiprofen and aspirin for postsurgical dental pain.
The analgesic efficacy of flurbiprofen 25 mg and 50 mg compared with aspirin 650 mg and placebo (lactose) was evaluated. Subjects were 164 dental outpatients undergoing the surgical removal of impacted teeth. Each subject received a single dose of study medication and was evaluated hourly for six hours. Aspirin was superior to placebo in all measures of analgesic efficacy, and both dosages of flurbiprofen were superior to aspirin.


Assessing and improving the outcomes of nonpoint source water quality trading policies in urban areas: A case study in Virginia.
Nonpoint source (NPS) water quality trading (WQT) is a market-based approach to improving water quality. Past work has shown that these programs could increase localized pollutant loadings, in part by exporting water quality controls from urban to rural areas. Virginia's NPS WQT program has enabled thousands of transactions and may provide a model for other programs, but its impacts on urban water quality have not been thoroughly assessed. We quantify the impact of NPS WQT purchases in Virginia on water quality and hydrology in an urban catchment. We go on to assess outcomes of a policy alternative where buyers and sellers are collocated in the urban catchment. Simulation results show that NPS WQT increased total phosphorus (TP) loading by an average of 0.8 lbs TP/year for each 1.0 offsite credits purchased in the analyzed catchment. The TP loading increased in years with greater rainfall, such that TP loads were increased by up to 1.2 lbs TP/year for each offsite credit purchased. These loading increases may or may not be acceptable, depending on the cumulative number of purchases within an urban catchment and existing local water quality issues. In our policy alternative with buyers and sellers collocated in the catchment, we found that the TP increase from development was completely offset at the catchment scale, with a decrease of 4.3 lbs TP/year for each 1.0 credits purchased. This suggests that credits awarded for urban mitigation practices are undervalued compared with water quality requirements for credit purchasers. This undervaluation is a result of the Virginia trading program using one approach to compute the credit value for buyers and a different approach to compute the credit value for sellers. We demonstrate how using a single model to determine both buyer and seller credit values in urban areas could provide greater transparency and mitigate the risk of urban pollution hot spots. This work demonstrates the importance of consistency in the scale of pollutant load calculations between buyers and sellers for NPS WQT, and contributes novel insight into the implications of WQT for urban NPS pollution.


Production of chitin and bioactive materials from Black tiger shrimp (Penaeus monodon) shell waste by the treatment of bacterial protease cocktail.
The main objective of this study was to obtain chitin in pure form from a new crustacean waste material for industrial applications. Black tiger shrimp shell wastes are a rich source of protein and valuable bioactive carbohydrate polymers such as chitin. After removal of carotenoid, Black tiger shrimp shell wastes (BTSHWs) were treated with chemicals and protease enzyme to extract chitin. Box-Behnken response surface methodology was applied to optimize the deproteinization process to obtain chitin. At optimal pH (8.82), temperature (50.05 °C), agitation speed (100.98 rpm), enzyme substrate ratio of 1:8 (wv-1) and 72 h of incubation with Paenibacillus woosongensis TKB2 crude protease cocktail, 80 % deproteinization was found along with 77.28 % recovery of chitin. The valuable oligopeptides were determined by MALDI-TOF analysis and analysis of adequate amount of free amino acids in protein hydrolysate from BTSHW, indicating a high nutritional value used for food, feed or as a nitrogen source in growth medium for microorganisms. The chitin obtained was compared with the commercial chitin using scanning electron microscopy, Fourier transform infrared spectrometer, X-ray diffraction and 13C CP/MAS-NMR. Chitin obtained from crude protease treatment showed comparable physicochemical and structural properties to those of the commercial chitin. The carotenoid obtained after treatment can be used for medicinal purpose.


Factorial structure of the manic-depressiveness scale in American college students.
In a sample of 503 American college students, the correlational matrix (18 x 18) of the Thalbourne, et al. Manic-Depressiveness Scale (1994) was subjected to exploratory factor analysis with a varimax rotation, which showed 13 items had the correct assignment to one of the scales (six for depression and seven for mania).


Dry heating treatment: A potential tool to improve the wheat starch properties for 3D food printing application.
The futuristic technology of three-dimensional (3D) printing is an additive manufacturing that allows obtaining creative and personalized food products. In this context, the study of food formulations (named as "inks") to be processed through 3D printing is necessary. This work investigated the use of dry heating treatment (DHT), a simple and safe method, to improve the wheat starch properties aiming to produce hydrogels to be used as "inks" for 3D printing. Wheat starch was processed by dry heating for 2 (DHT_2h) and 4 h (DHT_4h) at 130 °C. Modified wheat starches showed an increase in granule size, but processing did not alter the granule's shape nor surface, neither alter the molecular functional groups. On the other hand, DHT promoted slight molecular depolymerization, and reduction of starch crystallinity. Hydrogels "inks" based on the modified starches showed lower peak apparent viscosity during pasting, higher structural strength at rest, higher resistance to external stresses, higher gel firmness, and lower syneresis than hydrogels based on native starch. The hydrogels based on starch DHT_4h showed the best printability (greater ability to make a 3D-object by layer-by-layer deposition and to support its structure once printed) and this "ink" showed better reproducibility. Another point observed is that DHT extended the texture possibilities of printed samples based on wheat starch hydrogels. These results suggested that DHT is a relevant process to improve the properties of hydrogels based on wheat starch, making this ink suitable for 3D printing application.


Unspliced XBP1 controls autophagy through FoxO1.
Protein homeostasis in higher eukaryotes is balanced by a dynamic network of adaptive mechanisms, including the unfolded protein response (UPR) and autophagy. In a paper recently published in Cell Research, Zhu and co-workers uncover a novel biological function of the unspliced form of the UPR transcription factor XBP1 in the modulation of autophagy through the control of FoxO1 turnover.


A simple method for high molecular-weight genomic DNA extraction suitable for long-read sequencing from spores of an obligate biotroph oomycete.
Long-read sequencing technologies are having a major impact on our approaches to studying non-model organisms and microbial communities. By significantly reducing the cost and facilitating the genome assembly pipelines, any laboratory can now develop its own genomics program regardless of the complexity of the genome studied. The most crucial current challenge is to develop efficient protocols for extracting genomic DNA (gDNA) with high quality and integrity adapted to the organism of interest. This can be particularly complex for obligate pathogens that must maintain intimate interactions inside infected host tissues. Here we propose a simple and cost-effective method for high molecular weight gDNA extraction from spores of Plasmopara halstedii, an obligate biotroph oomycete pathogen responsible for downy mildew in sunflower. We optimized the yield, the quality and the integrity of the extracted gDNA by fine-tuning three critical parameters, the grinding, the lysis temperature and the lysis duration. We obtained gDNA with a fragment size distribution reaching a peak ranging from 79 to 145 kb. More than half of the extracted gDNA consisted of DNA fragments larger than 42 kb, with 23% of fragments larger than 100 kb. We then demonstrated the relevance of this protocol for long-read sequencing using PacBio RSII technology. With this protocol, we were able to obtain a mean read length of 9.3 kb, a max read length of 71 kb and an N50 of 13.3 kb. The development of such DNA extraction protocols is an essential prerequisite for fully exploiting technologies requiring high molecular weight gDNA (e.g. long-read sequencing or optical mapping). These technological advances will help generate data to answer questions such as the role of newly duplicated gene clusters, repeated regions, genomic structural variations or to define number of chromosomes that still remains undefined in many species of pathogenic fungi and oomycetes.


Gas-liquid chromatographic analysis of the monosaccharide composition of acid glycosaminoglycans (mucopolysaccharides) derived from animal tissues.
Quantitative, gas-liquid chromatography was investigated for analysis of the monosaccharide composition of acid mucopolysaccharides from animal tissues. The method entailed the analysis of the trimethylsillyl (Me3Si) derivatives of methyl glycosides on two liquid phases. Good resolution of monosaccharides was achieved by use of columns of SE-30 and Apiezon-M. The procedure was tested with chondroitin 4-sulfate, and the results were slightly different from those of Mathews et al. When the analysis is performed according to this method, important points are: (1) absolutely anhydrous, methanolic hydrogen chloride is necessary, to ensure detection of hexosamines and sialic acid; and (2) high moisture in the air obstructs high recovery of methyl glycosides and their Me3Si derivatives, except in the case of neutral sugars.


Potent immunogenicity of an HIV-1 gag-pol fusion DNA vaccine delivered by in vivo electroporation.
A plasmid DNA vaccine containing a fusion gene consisting of an HIV-1 subtype C gag and a modified subtype C pol was compared to a mixture of gag plus pol or gag plus HIV env plasmids. Plasmid DNA was delivered by intramuscular injection followed by electroporation in vivo. Two vaccinations were sufficient to induce high levels of Gag- and Pol-specific CD4 and CD8 T cells in peripheral blood. The gag-pol fusion plasmid was as immunogenic as the plasmid mixtures. Thus, DNA vaccination by intramuscular electroporation was an effective means for inducing high levels of Gag- and Pol-specific T cells, and a single gag-pol fusion DNA vaccine was sufficient for eliciting immune responses against both antigens.


The neuroanatomy of genetic subtype differences in Prader-Willi syndrome.
Despite behavioral differences between genetic subtypes of Prader-Willi syndrome (PWS), no studies have been published characterizing brain structure in these subgroups. Our goal was to examine differences in the brain structure phenotype of common subtypes of PWS [chromosome 15q deletions and maternal uniparental disomy 15 (UPD)]. Fifteen individuals with PWS due to a typical deletion [(DEL) type I; n = 5, type II; n = 10], eight with PWS due to UPD, and 25 age-matched healthy-weight individuals (HWC) participated in structural magnetic resonance imaging (MRI) scans. A custom voxel-based morphometry processing stream was used to examine regional differences in gray and white matter volume (WMV) between groups, covarying for age, sex, and body mass index (BMI). Overall, compared to HWC, PWS individuals had lower gray matter volumes (GMV) that encompassed the prefrontal, orbitofrontal and temporal cortices, hippocampus and parahippocampal gyrus, and lower WMVs in the brain stem, cerebellum, medial temporal, and frontal cortex. Compared to UPD, the DEL subtypes had lower GMV primarily in the prefrontal and temporal cortices, and lower white matter in the parietal cortex. The UPD subtype had more extensive lower gray and WMVs in the orbitofrontal and limbic cortices compared to HWC. These preliminary findings are the first structural neuroimaging findings to support potentially separate neural mechanisms mediating the behavioral differences seen in these genetic subtypes.


The demographic distribution of drinking patterns in 1984.
The demographic distribution of drinking and heavy drinking in a 1984 survey are presented to provide updated prevalence estimates for these phenomena. Several measures of drinking patterns are used, including: the frequency of drinking, the monthly volume consumed, the frequency of drinking five or more drinks on an occasion, the frequency of drinking eight or more drinks in a day, and the frequency of self-reported drunkenness. In most cases, the present results confirm earlier findings. However, the present data give better information on Black and Hispanic drinking patterns than was available in earlier surveys. Results not consistent with earlier studies are that there are contradictory findings regarding the relationship between socio-economic status and drinking and that the drinking patterns of divorced and separated men diverge from those of divorced and separated women.


Repeated treatments with botulinum toxin type a produce sustained decreases in the limitations associated with focal upper-limb poststroke spasticity for caregivers and patients.
To assess the safety and evaluate the effects of repeated treatments with botulinum toxin type A (BTX-A) on functional disability, quality of life (QOL), and muscle tone of patients with upper-limb poststroke spasticity, as well as its effect on caregivers. Multicenter, open-label, repeated-dose study. Thirty-five clinical sites in North America. Patients (N=279) with upper-limb poststroke spasticity at 6 months or more poststroke. Up to 5 intramuscular injections of BTX-A (200-400U) divided among the wrist, finger, thumb, and elbow flexors, with at least 200U in the wrist and finger flexors. Retreatment was permitted at 12 weeks or more after the last treatment. Investigators rated disability using the Disability Assessment Scale and muscle tone using the Ashworth Scale. Each patient's health-related QOL was assessed by using the Stroke Adapted Sickness Impact Profile and the visual analog scale of the European Quality of Life-5 Dimensions questionnaires. Patients treated with BTX-A reported improvements in muscle tone, disability, and ability to function that were statistically significant and clinically meaningful. Significant improvements were observed at week 30 and at subsequent time points in QOL in the overall group and the high-dose group. Up to 5 treatments with BTX-A every 12 weeks for up to 56 weeks in patients with poststroke spasticity was well tolerated and significantly improved muscle tone, lessened disability, and improved patients' QOL. Further research is required to examine the effectiveness of repeated injections of BTX-A in patients with poststroke spasticity.


Stimulation of IgG production by glucocorticoids in human myeloma lymphoblasts.
LICR-LON-HMy2 cells (HMy2 cells), an established line of human myeloma lymphoblasts, produce and secrete IgG, and have been used for production of human-human hybridomas. We have previously shown that HMy2 cells are growth-inhibited by glucocorticoids and contain high affinity, saturable, steroid-specific glucocorticoid receptors. Here we report that treatment for 0-4 days with the synthetic glucocorticoid dexamethasone (1,4-pregnadien-9-fluoro-16 alpha-methyl-11 beta,17 alpha,21-triol-3,20-dione) leads to time-dependent increases in IgG secretion rates as measured by goat anti-human IgG antibodies in an enzyme-linked immunosorbent assay. Stimulation of IgG secretion is dependent on the concentration of dexamethasone employed, with half-maximal stimulation occurring between 1.10(-9) and 1.10(-8) M, and maximal stimulation occurring at 1.10(-7) M. Stimulation of IgG secretion is specific for active glucocorticoids such as cortisol and dexamethasone; treatment of cells with 17 beta-estradiol, progesterone, dihydrotestosterone, and aldosterone has little, if any, effect on IgG secretion. Finally, dexamethasone markedly stimulates both secreted and newly synthesized IgG, as determined by continuous and pulse labeling of extracellular and intracellular proteins, respectively, followed by binding to protein A-Sepharose, gel electrophoresis, and autoradiography. Thus, although dexamethasone effects on post-translational or secretory processes have not been ruled out, our data indicate that increased biosynthesis of IgG accounts for most, if not all, of the observed increase in IgG secretion rates. In summary our results demonstrate that despite the known immunosuppressive effects of glucocorticoids, these hormones can stimulate IgG biosynthesis and secretion in human myeloma lymphoblasts in vitro.


Argentinean species of Chalarus Walker (Diptera: Pipunculidae): new records and description of Chalarus tani n. sp.
The Argentinean species of Chalarus Walker were studied. Pipunculidae adults belonging to four species, C halarus chilensis Collin, Chalarus triramosus Rafael, Chalarus absonus Rafael and Chalarus tani n. sp. were described based on two male specimens collected in the La Rioja and Tucuman Provinces, northwestern region of Argentina. Chalarus absonus is recorded for the first time in Argentina. New distributional data and an identification key to the adult males of the Argentinean representatives are provided including figures.