Randomized Controlled Trial of Web-Based Psychoeducation for Women With Borderline Personality Disorder.
To determine if internet-based psychoeducation for borderline personality disorder is effective in reducing symptom severity and improving psychosocial functioning. Eighty women who met DSM-IV criteria for borderline personality disorder were randomly assigned either to the internet-based psychoeducation treatment group (n = 40) or to the internet-based control group with no psychoeducation (n = 40). Recruitment was conducted from July 2013 to March 2015. Subjects participated in 15 assessment periods that were divided into an acute phase (weeks 1-12) and a maintenance phase (months 6, 9, and 12). Main outcomes were assessed using the Zanarini Rating Scale for Borderline Personality Disorder. In the acute phase, women in the treatment group were found to have a significant decline in their scores on all 10 outcomes studied, while women in the control group had a significant decline on 7 of these outcomes. Two between-group differences were found to be significant-those in the treatment group reported a significantly greater decline in their impulsivity (z = -1.98, P = .048) and a significantly greater increase in their psychosocial functioning (z = -1.97, P = .049) than those in the control group. In the maintenance phase, those in the treatment group were found to have a significant decline in their scores on 9 of the 10 outcomes studied, while those in the control group had a significant decline in 3 of these outcomes. In terms of between-group differences, those in the treatment group reported a significantly greater decline in all 5 studied areas of borderline psychopathology: affective symptoms (z = -2.31, P = .021), cognitive symptoms (z = -3.20, P = .001), impulsivity (z = -2.44, P = .015), interpersonal difficulties (z = -2.15, P = .032), and overall borderline personality disorder symptoms (z = -2.11, P = .035). Taken together, these results suggest that internet-based psychoeducation is an effective form of early treatment for reducing the symptom severity of borderline personality disorder for periods up to 1 year. ClinicalTrials.gov identifier: NCT01719731.


Opinions and attitudes of obstetricians and midwives in Turkey towards caesarean section and vaginal birth following a previous caesarean section.
Aim To determine the opinions and attitudes of Turkish obstetricians and midwives to caesarean section (C-section) and vaginal birth following a C-section. Methods The study involved obstetricians and midwives who were working in a state women's hospital and two private hospitals in Gaziantep, Turkey. Participants were asked to complete questionnaires on sociodemographic data and provide opinions about C-section. Results A total of 88 midwives and 22 obstetricians participated in the study. Approximately one-third of midwives believed caesarean rates were high at their institution and more than 50% thought that the rate should be reduced. In contrast, although approximately 80% of obstetricians thought that caesarean rates in their institutions ranged between 25-50%, only 18% believed the rate was high and 68% believed that the rate of should be reduced. Midwives and obstetricians tended to agree on most suggested reasons for high C-section rates. When asked about interventions that may reduce the C-section rates, midwives and obstetricians had opposing views. However, most participants agreed that prenatal childbirth preparation courses would be beneficial. Conclusions This study showed that most midwives and obstetricians believe the rate of C-section at their institution is high and should be reduced.


Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women: a randomized controlled trial.
Postmenopausal estrogen therapy has been posited to have some beneficial effects on aging processes, but its use has risks. Isoflavones, estrogenlike compounds naturally occurring in plant foods, might confer positive effects with fewer adverse effects. To investigate whether soy protein with isoflavones improves cognitive function, bone mineral density, and plasma lipids in postmenopausal women. Double-blind, randomized, placebo-controlled trial of 202 healthy postmenopausal women aged 60 to 75 years, recruited from a population-based sample in the Netherlands, conducted between April 2000 and September 2001. Participants were randomly assigned to receive 25.6 g of soy protein containing 99 mg of isoflavones (52 mg genistein, 41 mg daidzein, and 6 mg glycetein or total milk protein as a powder on a daily basis for 12 months. Cognitive function was assessed using the following instruments: dementia, Mini-Mental State Examination; memory, Rey Auditory Verbal Learning Test, immediate recall, delayed recall, and recognition, the Digit Span forward and reversed, and the Doors test; complex attention tasks, Digit Symbol Substitution and Trailmaking, A1, A2, and B; and verbal skills, Verbal Fluency A and N, animals and occupations, and the Boston Naming Task. Bone mineral density of the hip and lumbar spine was assessed using dual-energy x-ray absorptiometry scanning. Lipid assessment included lipoprotein(a), total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglycerides. A total of 175 women completed the baseline and at least 1 postintervention analysis and were included in the modified intent-to-treat analysis. Adherence was good (median plasma genistein levels, 17.2 and 615.1 nmol/L for placebo and soy group, respectively). Cognitive function, bone mineral density, or plasma lipids did not differ significantly between the groups after a year. This double-blind randomized trial does not support the hypothesis that the use of soy protein supplement containing isoflavones improves cognitive function, bone mineral density, or plasma lipids in healthy postmenopausal women when started at the age of 60 years or later.


Optimization of self-microemulsifying drug delivery systems (SMEDDS) using a D-optimal design and the desirability function.
D-optimal design and the desirability function were applied to optimize a self-microemulsifying drug delivery system (SMEDDS). The optimized key parameters were the following: 1) particle size of the dispersed emulsion, 2) solubility of the drug in the vehicle, and 3) the vehicle compatibility with the hard gelatin capsule. Three formulation variables, PEG200, a surfactant mixture, and an oil mixture, were included in the experimental design. The results of the mathematical analysis of the data demonstrated significant interactions among the formulation variables, and the desirability function was demonstrated to be a powerful tool to predict the optimal formulation for the explored system.


The prevalence of temporomandibular disorder and temporomandibular morphology among diverse chronotype profiles.
This study investigates the influence of chronotype on the prevalence of temporomandibular joint disorders (TMD) and the morphology of temporomandibular joint (TMJ). According to the Morningness-Eveningness Questionnaire-Self-Assessment, the participants were divided into morning group (n = 30), intermediate group (n = 83), and evening group (n = 30). Thirty participants were randomly selected from the intermediate group for subsequent examination and measurements. The morphology of TMJs was investigated using questionnaire and clinical examination form in Diagnostic Criteria for Temporomandibular Disorder. Meanwhile, the morphological results of TMJs were measured from cone-beam computed tomography images. The prevalence rate of TMD in the morning group (23%) was significantly lower than that in the intermediate group (56.7%), while there was no difference between the evening (53.4%) and intermediate groups. As to morphological measurements, there was no significant difference among three groups in mediolateral width of condylar process, anteroposterior width of condylar process, radius of condyle, medial joint space, lateral joint space, condylar stress angle, horizontal condylar inclination, width of glenoid fossa, depth of glenoid fossa, and posterior joint space, while there was a significant difference in horizontal condylar angle (p = 0.00490), articular eminence inclination (p < .0001), anterior joint space (p = 0.0163), and superior joint space (p = 0.0004). The morphology of TMJ in the morning group was better than that in the evening and intermediate groups. An association was found between TMD prevalence, temporomandibular morphology, and chronotype.


Spin/Valley Coupled Dynamics of Electrons and Holes at the MoS2-MoSe2 Interface.
The coupled spin and valley degrees of freedom in transition metal dichalcogenides (TMDs) are considered a promising platform for information processing. Here, we use a TMD heterostructure MoS2-MoSe2 to study optical pumping of spin/valley polarized carriers across the interface and to elucidate the mechanisms governing their subsequent relaxation. By applying time-resolved Kerr and reflectivity spectroscopies, we find that the photoexcited carriers conserve their spin for both tunneling directions across the interface. Following this, we measure dramatically different spin/valley depolarization rates for electrons and holes, ∼30 and <1 ns-1, respectively, and show that this difference relates to the disparity in the spin-orbit splitting in conduction and valence bands of TMDs. Our work provides insights into the spin/valley dynamics of photoexcited carriers unaffected by complex excitonic processes and establishes TMD heterostructures as generators of spin currents in spin/valleytronic devices.


Distal duodenal carcinoma and intussusception.
Adenocarcinoma of the duodenum is an uncommon malignancy that usually presents itself with either obstructive symptoms or jaundice, depending on its location. The diagnosis should be suspected in any patient with a high small bowel obstruction, weight loss, or chronic abdominal pain. Endoscopy and barium contrast x-ray films are the preferred initial studies; enteroclysis may provide additional information. Surgical resection offers the only hope for long-term survival, which should approach 50% with resectable tumors.


Escherichia coli succinyl coenzyme A synthetase. Inhibition of ATP-stimulated succinate----succinyl coenzyme A exchange at low succinyl coenzyme A concentrations by an ADP trap.
The hypothesis that Escherichia coli succinyl-CoA synthetase functions by a cooperative alternating sites mechanism is based largely on the results of [18O]phosphate exchange experiments (Bild, G. S., Janson, C. A., and Boyer, P. D. (1980) J. Biol. Chem. 255, 8109-8115). In those experiments, [18O]Pi----succinate (predominantly) exchange appeared to proceed at greater rates (relative to the apparent amount of succinyl-CoA released from the enzyme) at low ATP in incubations containing ATP, CoA, succinate, [18O]Pi, 0.48 M hydroxylamine (as a succinyl-CoA trap), and a pyruvate kinase-lactate dehydrogenase ADP trap. The conclusion arrived at was that succinyl-CoA binding at one site was inversely related to ATP binding at the second site. Thus, the residence time of succinyl-CoA binding at a site would be longer at lower ATP concentrations. Our experiments show that, under the incubation conditions described by Bild et al. (Bild, G. S., Janson, C. A., and Boyer, P. D. (1980) J. Biol. Chem. 255, 8109-8115), succinyl-CoA is not efficiently trapped. Thus, at ATP concentrations from 3.6 to 150 microM, concentrations of succinyl-CoA from 13 to 78 microM were observed. Succinate----succinyl-CoA exchange reactions carried out in this range of ATP and subsaturating succinyl-CoA concentrations were found to be markedly inhibited by the addition of the ADP trap. This inhibition was more pronounced at higher ATP levels. At a saturating succinyl-CoA concentration (1.5 mM), addition of the ADP trap actually stimulated succinate----succinyl-CoA exchange. Under these conditions, ATP----Pi exchange was greatly depressed. These results are interpreted as follows. ADP is required for optimal binding of succinyl-CoA, but only when the latter is present at subsaturating concentrations; thus, the ADP trap inhibits the reaction. ATP exerts its stimulatory action on succinate---- succinyl-CoA exchange through an "other site" effect, i.e. in binding to the noncatalytic site of succinyl-CoA synthetase, it facilitates binding and release of succinyl-CoA at the catalytic site. ATP may also exert negative effects by inhibiting other site binding of ATP or by interfering with same site succinyl-CoA binding at subsaturating concentrations of the latter. These data support the notion that a half-sites mechanism applies to succinyl-CoA synthetase, but suggest that the [18O]Pi----succinate exchange data which have been instrumental in development of the cooperative alternating sites hypothesis should be re-evaluated.


How Different Genetically Manipulated Brassica Genotypes Affect Life Table Parameters of Plutella xylostella (Lepidoptera: Plutellidae).
The fitness of Plutella xylostella L. on different genetically manipulated Brassica plants, including canola's progenitor (Brassica rapa L.), two cultivated canola cultivars (Opera and RGS003), one hybrid (Hyula401), one gamma-ray mutant-RGS003, and one transgenic (PF) genotype was compared using two-sex and female-based life table parameters. All experiments were conducted in a growth chamber at 25±1°C, 65±5% relative humidity, and a photoperiod of 16:8 (L:D) h. There were significant differences in duration of different life stages of P. xylostella on different plant genotypes. The shortest (13.92 d) and longest (24.61 d) total developmental time were on Opera and PF, respectively. The intrinsic rate of increase of P. xylostella ranged between 0.236 (Opera) and 0.071 day(-1) (PF). The highest (60.79 offspring) and lowest (7.88 offspring) net reproductive rates were observed on Opera and PF, respectively. Comparison of intrinsic rate of increase, net reproductive rates, finite rate of increase, mean generation time, fecundity, and survivorship of P. xylostella on the plant genotypes suggested that this pest performed well on cultivars (RGS003 and Opera) and performed poorly on the other manipulated genotypes especially on mutant-RGS003 and PF. Glucosinolate levels were significantly higher in damaged plants than undamaged ones and the lowest and highest concentrations of glucosinolates were found in transgenic genotype and canola's progenitor, respectively. Interestingly, our results showed that performance and fitness of this pest was better on canola's progenitor and cultivated plants, which had high levels of glucosinolate.


Silver-staining patterns of mammalian epididymal spermatozoa.
Epididymal spermatozoa from 12 species of mammals were stained using silver nitrate and examined with the light microscope. Silver nitrate differentiates many of the gross morphological features of spermatozoa, including the acrosome, subacrosomal region, perforatorium, postacrosomal sheath, neck, dense outer fibers of the core of the midpiece, annulus, principal piece, and end piece. Silver-staining patterns of spermatozoa reveal both species-specific and strain-specific differences, particularly of the sperm head. The biochemical basis of silver staining may be due in part to the presence of sulfhydryl- and disulfide-rich proteins; however, it cannot be explained entirely by the presence of these moieties. The detail obtained using silver nitrate staining, coupled with the ease and rapidity of the procedure, should be useful to workers in many areas of biological and medical research.


Personal history and quality of life in chronic myeloid leukemia patients: a cross-sectional study using narrative medicine and quantitative analysis.
Tyrosine kinase inhibitors (TKIs) drastically changed the outcome of patients diagnosed with chronic myeloid leukemia (CML). Several reports indicated the advantage of continue long-term adherence associated with positive outcome. Therefore, it is important to better understand from the patient's standpoint the experience of living with the disease and the related treatment. In this study, quantitative analysis and narrative medicine were combined to get insights on this issue in a population of 257 patients with CML in chronic phase treated with TKIs (43 % men, with a median age of 58 years, 27 % aged 31-50 years), followed for a median time of 5 years. Sixty-one percent of patients enrolled were treated in first line, whereas 37 % were treated in second line. The results showed more positive perceptions and acceptance in males compared to females, without impact of disease on relationships. Level of positive acceptance was more evident in elderly compared to younger patients, with a close connection with median time from diagnosis. Overall, female patients reported negative perceptions and an impact of disease on family daily living. The majority of patients understood the importance of continue adherence to treatment, with 27 % resulting less adherent (60 % for forgetfulness), even if well informed and supported by his/her physician. Narrative medicine, in association to quantitative analysis, can help physicians to understand needs of their patients in order to improve communication.


Hb mass measurement suitable to screen for illicit autologous blood transfusions.
An increase of hemoglobin (Hb) mass is the key target of blood doping practices to enhance performance as it is a main determinant of maximal oxygen uptake. Although detection methods exist for doping with recombinant EPO and homologous blood transfusions, autologous transfusions remain virtually undetectable. In this context, the most sensitive parameter would be a determination of Hb mass itself. The purpose therefore was to establish whether Hb mass measurements by the optimized CO-rebreathing method allow screening for the withdrawal and reinfusion of autologous red blood cells. The optimized CO-rebreathing method was used for evaluation of Hb mass in two groups at three time points (duplicate measurements: 1) baseline, 2) after donation, and 3) after reinfusion). Group I (N = 6) was to donate and receive 1 unit of packed red cells (PRC) in contrast to two PRC in group II (N = 4). The time span between withdrawal and reinfusion was 2 d. The mean Hb content of the blood units was 59.0 +/- 3.9 g (group I) and 108.3 +/- 1.3 g (group II). Hb mass decreased significantly after blood withdrawal (-89 +/- 16 g in group I and -120 +/- 14 g in group II) and increased significantly after reinfusion (group I: 70 +/- 16 g; group II: 90 +/- 9 g) but was lower than at baseline (group I: -19 +/- 17 g; group II: -30 +/- 14 g). The total error of measurements for the duplicate measures ranged between 0.8 and 3.1% (Hb mass: 6.4-22.1 g). Hb mass determination with the optimized CO-rebreathing method has sufficient precision to detect the absolute differences in Hb mass induced by blood withdrawal and autologous reinfusion. Thus, it may be suited to screen for artificially induced alterations in Hb mass.


The differential effects of sarcopenia and cachexia on overall survival for pancreatic ductal adenocarcinoma patients following pancreatectomy: A retrospective study based on a large population.
Both cachexia and sarcopenia have been considered adverse predictors for prognosis in patients with pancreatic cancer; although sarcopenia and cachexia share some similarities, they are still defined as distinct nutritional conditions. We aimed to explore the differential impacts of sarcopenia and cachexia on prognosis for pancreatic ductal adenocarcinoma (PDAC) patients following radical excision. From January 2015 to May 2022, 614 patients undergoing surgery for PDAC were retrospectively included. Sarcopenia was defined as the L3 total skeletal muscle index below 52.4 cm2 /m2 (men) and 38.5 cm2 /m2 (women). Cachexia was classified according to the following criteria: involuntary weight loss >5% over the past 6 months, or weight loss >2% and BMI <20 kg/m2 , or weight loss >2% and sarcopenia. Of the 614 patients included in the analysis, 62% and 48% were diagnosed with sarcopenia and cachexia, respectively. Kaplan-Meier analysis showed that sarcopenia and/or cachexia were significantly associated with worse overall survival (OS) rather than worse recurrence-free survival (RFS). Moreover, Cox regression analysis revealed that cachexia rather than sarcopenia was an adverse factor for OS in all PDAC patients. For poorly differentiated PDAC, both cachexia and sarcopenia were significantly associated with shorter OS. However, for moderately/well-differentiated PADC, cachexia was an independent factor for adverse OS, but not sarcopenia. Sarcopenia and cachexia have different effects on OS for PDAC patients undergoing radical excision. This difference may provide some important information for preoperative management.


Hydrogen exchange differences between chemoreceptor signaling complexes localize to functionally important subdomains.
The goal of understanding mechanisms of transmembrane signaling, one of many key life processes mediated by membrane proteins, has motivated numerous studies of bacterial chemotaxis receptors. Ligand binding to the receptor causes a piston motion of an α helix in the periplasmic and transmembrane domains, but it is unclear how the signal is then propagated through the cytoplasmic domain to control the activity of the associated kinase CheA. Recent proposals suggest that signaling in the cytoplasmic domain involves opposing changes in dynamics in different subdomains. However, it has been difficult to measure dynamics within the functional system, consisting of extended arrays of receptor complexes with two other proteins, CheA and CheW. We have combined hydrogen exchange mass spectrometry with vesicle template assembly of functional complexes of the receptor cytoplasmic domain to reveal that there are significant signaling-associated changes in exchange, and these changes localize to key regions of the receptor involved in the excitation and adaptation responses. The methylation subdomain exhibits complex changes that include slower hydrogen exchange in complexes in a kinase-activating state, which may be partially consistent with proposals that this subdomain is stabilized in this state. The signaling subdomain exhibits significant protection from hydrogen exchange in complexes in a kinase-activating state, suggesting a tighter and/or larger interaction interface with CheA and CheW in this state. These first measurements of the stability of protein subdomains within functional signaling complexes demonstrate the promise of this approach for measuring functionally important protein dynamics within the various physiologically relevant states of multiprotein complexes.


Silver colloidal nanoparticles: antifungal effect against adhered cells and biofilms of Candida albicans and Candida glabrata.
The aim of this study was to evaluate the effect of silver nanoparticles (SN) against Candida albicans and Candida glabrata adhered cells and biofilms. SN (average diameter 5 nm) were synthesized by silver nitrate reduction with sodium citrate and stabilized with ammonia. Minimal inhibitory concentration (MIC) tests were performed for C. albicans (n = 2) and C. glabrata (n = 2) grown in suspension following the Clinical Laboratory Standards Institute microbroth dilution method. SN were applied to adhered cells (2 h) or biofilms (48 h) and after 24 h of contact their effect was assessed by enumeration of colony forming units (CFUs) and quantification of total biomass (by crystal violet staining). The MIC results showed that SN were fungicidal against all strains tested at very low concentrations (0.4-3.3 μg ml(-1)). Furthermore, SN were more effective in reducing biofilm biomass when applied to adhered cells (2 h) than to pre-formed biofilms (48 h), with the exception of C. glabrata ATCC, which in both cases showed a reduction ∼90%. Regarding cell viability, SN were highly effective on adhered C. glabrata and respective biofilms. On C. albicans the effect was not so evident but there was also a reduction in the number of viable biofilm cells. In summary, SN may have the potential to be an effective alternative to conventional antifungal agents for future therapies in Candida-associated denture stomatitis.


Combined immuno-purification and detection of recombinant erythropoietins and activin receptor type II-Fc fusion proteins by isoelectric focusing for application in doping control.
Iso-electric focusing (IEF) was the first method established to discriminate endogenous and recombinant erythropoietins (rEPOs). It is still approved by the World Anti-Doping Agency (WADA) as an initial testing procedure to detect erythropoiesis stimulating agents (ESAs) in doping control samples. However EPO-Fc, one of the prohibited rEPOs designated by WADA, is not detectable with the actual IEF conditions. Other newly developed ESAs - luspatercept and sotatercept, both activin receptor type II-Fc fusion proteins (ActRII-Fc) - are also now prohibited and could be used in combination with rEPOs. Methods of identification of ActRII-Fc in blood by SAR/SDS-PAGE have been described, but not by IEF. Here we detail improvements in blood sample preparation and IEF analysis: A combined immuno-purification of EPOs and ActRII-Fc proteins in a single procedure, an appropriate isoforms separation for all proteins using new pre-loading and gel conditions, and a single detection of all rEPOs and ActRII-Fc proteins after successive incubation with anti-EPO and anti-ActRII antibodies. With these changes, distinctive profiles for all the ESAs were obtained by IEF. Therefore, IEF could be used as a screening method to detect a wide spectrum of prohibited ESAs in blood samples prior to specific confirmation for the identified rEPO or ActRII-Fc.


Long-range GABAergic neurons in the prefrontal cortex modulate behavior.
Cortical glutamatergic projections are extensively studied in behavioral neuroscience, whereas cortical GABAergic projections to downstream structures have been overlooked. A recent study by Lee and colleagues (Lee AT, Vogt D, Rubenstein JL, Sohal VS. J Neurosci 34: 11519-11525, 2014) used optogenetic and electrophysiological techniques to characterize a behavioral role for long-projecting GABAergic neurons in the medial prefrontal cortex. In this Neuro Forum, we discuss the potential implications of this study in several learning and memory models.


Rapid Gut Adaptation to Preterm Birth Involves Feeding-Related DNA Methylation Reprogramming of Intestinal Genes in Pigs.
Following preterm birth, the immature gut function and immunology must rapidly adapt to cope with bacterial colonization and enteral milk feeding. We hypothesized that intestinal epigenetic changes are involved in the gut response to preterm birth and the first feeding. Using piglets as models for infants, preterm, and term pigs were fed total parenteral nutrition (TPN) or partial enteral feeding for 5 days, followed by exclusive enteral feeding with bovine milk until day 26 (weaning age). Intestinal structure, function, microbiome, DNA methylome, and gene expressions were compared between preterm and term pigs on days 0, 5, and 26 (n = 8 in each group). At birth, the intestine of preterm pigs showed villus atrophy and global hypermethylation, affecting genes related to the Wnt signaling pathway. Hypermethylation-associated lowered expression of lipopolysaccharide-binding protein and genes related to the Toll-like receptor 4 pathway were evident during the first 5 days of life, but most early methylation differences disappeared by day 26. Regardless, sucrase and maltase activities (adult-type brush border enzymes) remained reduced, and the gut microbiota altered (fewer Akkermansia, more Lachnoclostridia and Lactobacilli) until day 26 in preterm pigs. During the 0- to 5-day period, many new preterm-term methylation differences appeared, but mainly when no enteral feed was provided (TPN feeding). These methylation differences affected intestinal genes related to cell metabolism, including increased GCK (glucokinase) expression via promoter hypomethylation. In conclusion, the immature intestine has a remarkable capacity to adapt its gene methylation and expression after preterm birth, and only few preterm-related defects persisted until weaning. Early enteral feeding may be important to stimulate the methylation reprogramming of intestinal genes, allowing rapid intestinal adaptation to preterm birth.


Stages of HIV replication and targets for therapeutic intervention.
The replication cycle of human immunodeficiency virus (HIV) is divided into an early and a late phase. Most of the steps of the cycle have been targeted in antiviral therapy, although the drugs currently available for clinical use are only effective against two replication enzymes of the virus, either against the reverse transcriptase or against the viral protease. The introduction of combination anti-retroviral therapy changed the prognosis of HIV infection. HIV-related morbidity and mortality rates in patients with advanced HIV infection have significantly declined. However, there are severe limits of HAART. Current anti-retroviral therapy do not allow viral eradication, therefore long-term use of the drugs is required. As a consequence, resistance develops in a significant portion of patients. Furthermore, several adverse metabolic side effects have been observed associated with the therapy. Therefore new approaches are required to control or eradicate this deadly virus infection.


Pertussis immunization: science and the public.
Problems with pertussis immunization are not unique to the developing world. Problems exist in at least six nations in the industrialized world, in five of which epidemic pertussis has either never been controlled or has recurred because of low rates of immunization against pertussis. The poor rates of immunization have resulted in several instances from decisions by health authorities and in others from public fear of vaccine reactions. In all instances poor understanding of science by the public and by decision makers has been a major contributing factor.


Circulating non-22-kilodalton growth hormone isoforms in acromegalic men before and after transsphenoidal surgery.
GH represents several molecular isoforms in addition to the main 22-kDa (22K) GH. There have been reports suggesting that circulating non-22K GH isoforms are increased in acromegaly, but the possible implications of such observations in the management of the disease have not been addressed. The aim of this study was to evaluate the proportion of circulating non-22K GH isoforms in acromegaly. In addition, the relationships between the amount of non-22K GH and tumor size, biochemical measurements, and body composition also were investigated. Samples with different GH levels were selected from 24-h GH profiles from 15 acromegalic men evaluated before and 1 yr after transsphenoidal surgery and from 13 healthy men. The serum non-22K GH levels, expressed as percentage of total GH concentration, were determined by the 22K GH exclusion assay, which is based on immunomagnetic extraction of 22K GH from serum and quantitation of non-22K GH using a polyclonal GH assay. The proportion of non-22K GH isoforms was fairly constant in different samples from the same patient, regardless of the GH level. However, a wide variation of values was observed among acromegalics, both before (14-51%) and after surgery (8-62%). The proportion of non-22K GH isoforms was increased in untreated patients, compared with controls (26.6 vs. 17.4%; P < 0.01), and the values correlated significantly to tumor size, mean 24-h GH concentration, serum PRL, and extracellular water. After surgery, patients not truly cured, with mean 24-h GH concentration of 1 microg/L or more, had an increased proportion of non-22K GH, compared with those with levels less than 1 microg/L (P < 0.01). In the former group, the median values were similar than those in untreated acromegalics (34 vs. 26.6%, respectively), whereas in the latter, they were comparable with those in the controls (15.2 vs. 17.4%, respectively). We conclude that acromegalics have an increased proportion of circulating non-22K GH isoforms. The values are fairly constant in different samples from an individual, regardless of GH level, but a large spectrum can be observed among patients. This variability suggests that different pituitary adenomas secrete GH isoforms in variable amounts. Our observation that a higher proportion of non-22K GH isoforms is present in patients not truly cured after surgery suggests that the evaluation of non-22K GH isoforms can be useful in the follow-up of acromegalic patients.


Improved synapse detection for mGRASP-assisted brain connectivity mapping.
A new technique, mammalian green fluorescence protein (GFP) reconstitution across synaptic partners (mGRASP), enables mapping mammalian synaptic connectivity with light microscopy. To characterize the locations and distribution of synapses in complex neuronal networks visualized by mGRASP, it is essential to detect mGRASP fluorescence signals with high accuracy. We developed a fully automatic method for detecting mGRASP-labeled synapse puncta. By modeling each punctum as a Gaussian distribution, our method enables accurate detection even when puncta of varying size and shape partially overlap. The method consists of three stages: blob detection by global thresholding; blob separation by watershed; and punctum modeling by a variational Bayesian Gaussian mixture models. Extensive testing shows that the three-stage method improved detection accuracy markedly, and especially reduces under-segmentation. The method provides a goodness-of-fit score for each detected punctum, allowing efficient error detection. We applied this advantage to also develop an efficient interactive method for correcting errors. The software is available on http://jinny.kist.re.kr.


Disability and countertransference in group psychotherapy: connecting social oppression with the clinical frame.
Psychoanalysis has paid limited attention to disability, and at times the approach has lacked political awareness. Over recent decades the international disability rights movement has argued that disabled people constitute an oppressed, systemically disadvantaged minority. Lately, a critical psychoanalytic view has connected disablist discrimination to universal unconscious conflicts evoked by impairment. Corresponding evocations emerge in the therapeutic frame, producing countertransference responses to the impaired body. Drawing on psychoanalytically oriented group psychotherapy with severely physically impaired adults, countertransference phenomena were studied in developing discussion on disability-related clinical work. The complex, uncertain role of psychoanalytic practice in combating oppression was also examined. Key issues include challenges to the traditional frame, the crossing of psychic boundaries, anxieties relating to not knowing, and the role of unconscious factors in marginalizing disabled experience.


Transcriptional corepressor SHP recruits SIRT1 histone deacetylase to inhibit LRH-1 transactivation.
Orphan nuclear receptor Small Heterodimer Partner (SHP; NR0B2) is a transcriptional corepressor of a wide variety of nuclear receptors (NRs). Here, we report that SHP recruits SIRT1, a class III histone deacetylase, in an NR-specific manner to inhibit transcriptional activity. SHP interacts and co-localizes specifically with SIRT1 in vivo and inhibition of SIRT1 activity leads to a recovery from the intrinsic repressive activity of SHP but not of DAX1. Furthermore, we observed that SIRT1 does not deacetylate SHP or LRH1. However, inhibition of either SIRT1 or SHP significantly diminished the repressive effect of SHP on LRH1 transactivity. LRH1-mediated activation of CYP7A1 and SHP gene transcription was significantly repressed by both SHP and SIRT1 whereas inhibition of SIRT1 activity by inhibitors or dominant negative SIRT1 or knockdown of SHP led to a significant release of this inhibitory effect. ChIP assays revealed that SHP recruits SIRT1 on LRH1 target gene promoters and SIRT1 deacetylated template-dependent histone H3 and H4 to inhibit transcription of LRH1 target genes. Finally, we demonstrated that inhibition of SIRT1 activity significantly reversed SHP-mediated inhibition of bile-acid synthesis by LRH1 overexpression, thereby suggesting a novel mechanism of SHP-mediated inhibition of LRH1-dependent bile-acid homeostasis via recruitment of SIRT1 histone deacetylase protein.


X-rays: laying the foundation of modern radiology, 1896-1930.
The authors describe the initial impact and far-reaching consequences of the discovery of x-rays in 1895. Roentgen was quick to realise the importance of this mysterious new kind of ray he had discovered. As early as 1896 x-rays were already being used in surgery and medicine, replacing Bell's telephonic needle probe, which could only detect metallic objects by sound and was therefore limited to the location of objects such as bullets for removel. As x-ray diagnosis became more accurate, radiological techniques were gradually improved over the years and progressed from examination of the skeleton to imaging complex internal organs. The x-ray became vital in the detection of tuberculosis, for which it is still used today. Through the use of opaque substances such as barium sulfate it became possible to visualise the digestive tract and later advances in photographic techniques made visible the brain and almost all parts of the body. Meanwhile the dangers of radiation were recognized and after 1930 safety measures were introduced to protect radiologists and patients against overexposure. In the hundred years since its discovery the ever-widening scope of radiology has made it a fundamental resource in medical diagnosis and treatment.


Assessing the perceived quality of brachial artery Flow Mediated Dilation studies for inclusion in meta-analyses and systematic reviews: Description of data employed in the development of a scoring ;tool based on currently accepted guidelines.
Brachial artery Flow Mediated Dilation (FMD) is widely used as a non-invasive measure of endothelial function. Adherence to expert consensus guidelines on FMD measurement has been found to be of vital importance to obtain reproducible data. This article lists the literature data which was considered in the development of a tool to aid in the objective judgement of the extent to which published studies adhered to expert guidelines for FMD measurement. Application of this tool in a systematic review of FMD studies (http://dx.doi.org/10.1016/j.atherosclerosis.2016.03.011) (Greyling et al., 2016 [1]) indicated that adherence to expert consensus guidelines is strongly correlated to the reproducibility of FMD data.


Peptide Scanning-assisted Identification of a Monoclonal Antibody-recognized Linear B-cell Epitope.
The identification of an antigenic epitope by the immune system allows for the understanding of the protective mechanism of neutralizing antibodies that may facilitate the development of vaccines and peptide drugs. Peptide scanning is a simple and efficient method that straightforwardly maps the linear epitope recognized by a monoclonal antibody (mAb). Here, the authors present an epitope determination methodology involving serially truncated recombinant proteins, synthetic peptide design, and dot-blot hybridization for the antigenic recognition of nervous necrosis virus coat protein using a neutralizing mAb. This technique relies on the dot-blot hybridization of synthetic peptides and mAbs on a polyvinylidene fluoride (PVDF) membrane. The minimum antigenic region of a viral coat protein recognized by the RG-M56 mAb can be narrowed down by step-by-step trimmed peptide mapping onto a 6-mer peptide epitope. In addition, alanine scanning mutagenesis and residue substitution can be performed to characterize the binding significance of each amino acid residue making up the epitope. The residues flanking the epitope site were found to play critical roles in peptide conformation regulation. The identified epitope peptide may be used to form crystals of epitope peptide-antibody complexes for an x-ray diffraction study and functional competition, or for therapeutics.


Traumatic Pseudoaneurysms of the Head in War Time: Report of Two Unusual Cases.
Either intracranial or extracranial pseudoaneurysms due to penetrating head injuries with gunshot are very rare entities. As the pseudoaneurysms of the superficial temporal artery are represented commonly with a pulsating mass lesion beneath scalp, the intracranial pseudoaneurysms are represented with symptoms including decreased conscious level, seizure, or focal neurological deficits. Here, two patients with combat related pseudoaneurysms are reported; one was in distal cortical branch of anterior cerebral artery and one was in superficial temporal artery. Both of the cases were victims of Libyan war. One was admitted with a swelling in his scalp and a pseudoaneurysms on parietal branch of superficial temporary artery diagnosed with computed tomography; and the other was incidentally diagnosed on distal cortical branch of anterior cerebral artery during operation for removal of an intracranial bullet. Both of the aneurysms treated with surgical excision without any complication.


Cell type specific gene expression analysis of prostate needle biopsies resolves tumor tissue heterogeneity.
A lack of cell surface markers for the specific identification, isolation and subsequent analysis of living prostate tumor cells hampers progress in the field. Specific characterization of tumor cells and their microenvironment in a multi-parameter molecular assay could significantly improve prognostic accuracy for the heterogeneous prostate tumor tissue. Novel functionalized gold-nano particles allow fluorescence-based detection of absolute mRNA expression levels in living cells by fluorescent activated flow cytometry (FACS). We use of this technique to separate prostate tumor and benign cells in human prostate needle biopsies based on the expression levels of the tumor marker alpha-methylacyl-CoA racemase (AMACR). We combined RNA and protein detection of living cells by FACS to gate for epithelial cell adhesion molecule (EPCAM) positive tumor and benign cells, EPCAM/CD45 double negative mesenchymal cells and CD45 positive infiltrating lymphocytes. EPCAM positive epithelial cells were further sub-gated into AMACR high and low expressing cells. Two hundred cells from each population and several biopsies from the same patient were analyzed using a multiplexed gene expression profile to generate a cell type resolved profile of the specimen. This technique provides the basis for the clinical evaluation of cell type resolved gene expression profiles as pre-therapeutic prognostic markers for prostate cancer.


[Influence of procaine and nicotinoyl-procaine on enzyme activities, nucleic acid and protein synthesis in primary cultures of heart and skeletal muscle cells of rats (author's transl)].
The comparative studies are continued on the influence of two tertiary amines, procaine and nicotinoyl-procaine, on isolated heart and skeletal muscle cells in culture. A daily addition of these substances to cell cultures produces an increase in the specific activities of glutamate dehydrogenase and glutamate-oxaloacetate transaminase and an inhibition of alteration in the isoenzyme pattern of lactate dehydrogenase. The presence of procaine or nicotinoyl-procaine, resp., inhibits thymidine incorporation by cells in culture, whereas the incorporation of thymidine is increased after pretreatment of cells with these substances. These results support the findings of an influence of said tertiary amines on the metabolism of cells in culture.


A large-scale assessment of European rabbit damage to agriculture in Spain.
Numerous small and medium-sized mammal pests cause widespread and economically significant damage to crops all over the globe. However, most research on pest species has focused on accounts of the level of damage. There are fewer studies concentrating on the description of crop damage caused by pests at large geographical scales, or on analysis of the ecological and anthropogenic factors correlated with these observed patterns. We investigated the relationship between agricultural damage by the European rabbit (Oryctolagus cuniculus) and environmental and anthropogenic variables throughout Spain. Rabbit damage was mainly concentrated within the central-southern regions of Spain. We found that rabbit damage increased significantly between the early 2000s and 2013. Greater losses were typical of those areas where farming dominated and natural vegetation was scarce, where main railways and highways were present, and where environmental conditions were generally favourable for rabbit populations to proliferate. From our analysis, we suggest that roads and railway lines act as potential corridors along which rabbits can spread. The recent increase in Spain of such infrastructure may explain the rise in rabbit damage reported in this study. Our approach is valuable as a method for assessing drivers of wildlife pest damage at large spatial scales, and can be used to propose methods to reduce human - wildlife conflict. © 2017 Society of Chemical Industry.


Evaluation of the Association of Transferrin Receptor Type 2 Gene Mutation (Y250X) with Iron Overload in Major β- Thalassemia.
Thalassemia is an inherited blood disorder in which the body produces defective hemoglobin. One of the important processes to reduce the complication of major β-thalassemia is blood transfusion that leads to elevated ferritin levels in the blood. Many patients who have major β-thalassemia may have hemochromatosis conditions resulting from iron metabolism disorders. In patients who have β-thalassemia, the mutation Y250X in the TFR2 gene may play a role in the incidence of hemochromatosis. This study aimed to determine the relationship between ferritin levels and Y250X mutation in major β-thalassemia patients. In the present study, 12 blood samples were divided into nine major β-thalassemia patients and three healthy controls. The DNA was isolated from blood samples and the amplification of the target region was performed based on the specific primers. Sanger sequencing was used to find genetic single nucleotide polymorphisms associated with iron overload. Blood parameters, such as hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, and serum ferritin levels were analyzed and the recorded data showed the following results: 8.1±0.8 g/dL, 84.6±5.5 fL, 27±0.7 pg, respectively. The recorded data showed that the mean serum ferritin level in major β-thalassemia patients was 1921.7±848 ng/mL. The Y250X mutation was not found in major β-thalassemia patients and healthy controls.


Transfer of language dominance.
It has been suggested that recovery from aphasia may depend on the ability of the nondominant hemisphere to subserve language functions. We describe a patient who illustrates a possible "transfer" of language dominance. The patients sustained two infarcts two years apart, one in each hemisphere, involving mirror image territories in the temporoparietal area. The clinical course of each infarct was almost identical, consisting of an initial Wernicke's aphasia which evolved into anomic aphasia during recovery.


EEC- and ADULT-associated TP63 mutations exhibit functional heterogeneity toward P63 responsive sequences.
TP63 germ-line mutations are responsible for a group of human ectodermal dysplasia syndromes, underlining the key role of P63 in the development of ectoderm-derived tissues. Here, we report the identification of two TP63 alleles, G134V (p.Gly173Val) and insR155 (p.Thr193_Tyr194insArg), associated to ADULT and EEC syndromes, respectively. These alleles, along with previously identified G134D (p.Gly173Asp) and R204W (p.Arg243Trp), were functionally characterized in yeast, studied in a mammalian cell line and modeled based on the crystal structure of the P63 DNA-binding domain. Although the p.Arg243Trp mutant showed both complete loss of transactivation function and ability to interfere over wild-type P63, the impact of p.Gly173Asp, p.Gly173Val, and p.Thr193_Tyr194insArg varied depending on the response element (RE) tested. Interestingly, p.Gly173Asp and p.Gly173Val mutants were characterized by a severe defect in transactivation along with interfering ability on two DN-P63α-specific REs derived from genes closely related to the clinical manifestations of the TP63-associated syndromes, namely PERP and COL18A1. The modeling of the mutations supported the distinct functional effect of each mutant. The present results highlight the importance of integrating different functional endpoints that take in account the features of P63 proteins' target sequences to examine the impact of TP63 mutations and the associated clinical variability.


RNA Binding Protein CUGBP1 Inhibits Liver Cancer in a Phosphorylation-Dependent Manner.
Despite intensive investigations, mechanisms of liver cancer are not known. Here, we identified an important step of liver cancer, which is the neutralization of tumor suppressor activities of an RNA binding protein, CUGBP1. The translational activity of CUGBP1 is activated by dephosphorylation at Ser302. We generated CUGBP1-S302A knock-in mice and found that the reduction of translational activity of CUGBP1 causes development of a fatty liver phenotype in young S302A mice. Examination of liver cancer in diethylnitrosamine (DEN)-treated CUGBP1-S302A mice showed these mice develop much more severe liver cancer that is associated with elimination of the mutant CUGBP1. Searching for mechanisms of this elimination, we found that the oncoprotein gankyrin (Gank) preferentially binds to and triggers degradation of dephosphorylated CUGBP1 (de-ph-S302-CUGBP1) or S302A mutant CUGBP1. To test the role of Gank in degradation of CUGBP1, we generated mice with liver-specific deletion of Gank. In these mice, the tumor suppressor isoform of CUGBP1 is protected from Gank-mediated degradation. Consistent with reduction of CUGBP1 in animal models, CUGBP1 is reduced in patients with pediatric liver cancer. Thus, this work presents evidence that de-ph-S302-CUGBP1 is a tumor suppressor protein and that the Gank-UPS-mediated reduction of CUGBP1 is a key event in the development of liver cancer.


Social reward anticipation in infants as revealed by event-related potentials.
Infants engage in gaze interaction from the early stage of life. Emerging studies suggest that infants may expect social reward of shared attention before looking to the same object with another person. However, it was unknown about the neural responses during the anticipation of social rewards before shared attention in infants. We tested infants' reward anticipations in the gaze cueing situation measured by event-related potentials in the social association learning task. Six- to ten-month-old infants (N = 20) repeatedly observed that a female predictively looked toward the animation position (valid condition) or another female looking away from the animation (invalid condition). It was posited that infants could learn associations between female faces and the event of shared attention. The results showed that the stimulus preceding negativity which reflects reward anticipation before the animation presentation was elicited in the second half of the learning phases in the valid condition. Additionally, after the presentation of the face, N290 was greater in the second half of the learning phase than in the first half in the valid condition. These results suggest that infants can anticipate social reward from gaze cues, and learning the gaze cueing validity may affect not only reward anticipation but face perception.


Poly(ADP-ribose). The most elaborate metabolite of NAD+.
One of the most drastic post-translational modification of proteins in eukaryotic cells is poly(ADP-ribosyl)ation, catalysed by a family enzymes termed poly(ADP-ribose) polymerases (PARPs). In the human genome, 18 different genes have been identified that all encode PARP family members. Poly(ADP-ribose) metabolism plays a role in a wide range of biological structures and processes, including DNA repair and maintenance of genomic stability, transcriptional regulation, centromere function and mitotic spindle formation, centrosomal function, structure and function of vault particles, telomere dynamics, trafficking of endosomal vesicles, apoptosis and necrosis. In this article, the most recent advances in this rapidly growing field are summarized.


What Is Wrong with Hyaluronic Acid Chemistry? A 15N/13C Solid-State NMR Re-Evaluation of Its Dopamine Conjugates.
In this work, a systematic 15N/13C solid-state NMR investigation is performed on three dopamine (DA) conjugates of hyaluronic acid, considered in both its native (HA) and NaIO4-oxidized (HAOx) forms. Two of them, here named HAEDC-DA and HAOx-DA, have been previously introduced as covalent conjugates involving DA amine nitrogen: the former by EDC-mediated amide bond formation, and the latter by reaction of the Schiff base with the aldehyde moieties presumed to exist in HAOx. The third conjugate, HA-DA, is reported here for the first time; it is obtained by simply mixing hyaluronan with DA∙HCl at pH 5. The 15N ss-NMR spectra were found to be consistent in all the systems, and the DA molecules were found to be in their charged -NH3+ form, which contradicts the HAEDC-DA/HAOx-DA covalent bonding schemes proposed in the literature. The 13C ss-NMR results add useful new insights into the structure and interaction patterns of the conjugates. All of our findings are relevant for future practical applications, for instance in developing novel HA-based hydrogels. In addition, the present study demonstrates the importance of using the most appropriate analytical tools when investigating composite systems due to the complexity of hyaluronic acid conjugates. Solid-state NMR proved essential to answering the question in the title: actually, there is nothing wrong with hyaluronic acid chemistry; the claimed covalent bonds between DA and the HA(HAOx) chain do not exist in these systems, because the conditions for their formation do not hold in practice.


Quick and hassle-free smartphone's RGB-based color to photocatalytic degradation rate assessment of malachite green dye in water by fluorescent Zr-N-S co-doped carbon dots.
Sunlight active blue emissive zirconium, nitrogen, and sulfur co-doped carbon dots (Zr-N-S-CDs) have been synthesized by microwave-induced pyrolysis for achieving efficient photocatalytic degradation of pollutant malachite green dye (MG) in water. Surface morphology studies using high-resolution transmission electron microscopy confirmed the formation of spherical-shaped CDs with an absorbance peak at 350 nm and emission peak at 437 nm in UV-vis and fluorescence spectroscopy, respectively. Surface functional groups, elemental composition, and metal/non-metal co-doping were confirmed by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. To understand the photocatalytic performance of Zr-N-S-CDs, various parameters, such as the source of energy, concentration of dye, catalyst dosage, and change in pH, were investigated. MG dye (20 ppm) at a pH 7 with 0.5 mg/mL of Zr-N-S-CDs could be photodegraded efficiently in 90 min under sunlight (99%) compared to dark and artificial light conditions. Moreover, real-time analysis of degradation rate could be conveniently calculated by integrating the colorimetric responses of MG dye with RGB values obtained by the "Color Picker" app of a smartphone. The degradation rate obtained using a smartphone (97.89%) was found to be in agreement with the UV-vis spectroscopy (99%), thus, providing a new, handy, and instrument-free route for speedy and quantitative estimation of the degradation of hazardous MG dye by Zr-N-S-CDs.


OK432-activated natural killer cells enhanced trastuzumab (Herceptin)-mediated antibody-dependent cellular cytotoxicity in patients with advanced cancer.
Adoptive immunotherapy using natural killer (NK) cells from cancer patients yielded only modest success. Whether Herceptin and OK432-activated NK cells (NK cells obtained by stimulating peripheral blood mononuclear cells with OK432 and interleukin-2) improve the outcome of adoptive immunotherapy against HER-2/neu positive tumor cells via antibody-dependent cellular cytotoxicity, was examined in vitro. A 51Cr release assay was performed to assess cytotoxicity. OK432-activated NK cells and lymphokine-activated killer (LAK) cells from healthy donors and cancer patients were used as effectors. Three cell lines expressing different amounts of HER-2/neu served as targets. In the case of effectors from patients, OK432-activated NK cells showed higher cytotoxicity than that of LAK cells, and the cytotoxicity of OK432-activated NK cells against the SK-BR-3 cell line (over-expressing HER-2/neu) was increased by Herceptin. Combination of Herceptin and OK432-activeted NK cells may improve the efficacy of the treatment for HER-2/neu-positive malignancy.


The exoskeleton of scorpions' pincers: Structure and micro-mechanical properties.
Since scorpions exist almost all over the world, some expected body differences exist among the species: undoubtedly, the most evident is the shape and size of their pincers or chelae. The scorpion chela is a multifunctional body component (e.g. attack/defense, mating and protection from the environment) that leads to the development of different stresses in the cuticle. How such stresses in the cuticle are accommodated by different chelae shape and size is largely unknown. Here we provide new comparative data on the hierarchical structure and mechanical properties of the chela cuticle in two scorpion species: Scorpio Maurus Palmatus (SP) that has a large chela and Buthus Occitanus Israelis (BO), with a slender chela. We found that the SP exocuticle is composed of four different sublayers whereas the BO exocuticle displays only two sublayers. These structures are different from the exocuticle morphologies in crustaceans, where the Bouligand morphology is present throughout the entire layer. Moreover, the scorpion chela cuticle presents an exclusive structural layer made of unidirectional fibers arranged vertically towards the normal direction of the cuticle. Nanoindentation measurements were performed under dry conditions on transversal and longitudinal planes to evaluate the stiffness and hardness of the different chela cuticle layers in both scorpions. The chela cuticle structure is a key factor towards the decision of the scorpion whether to choose to sting or use the chela for other mechanical functions. STATEMENT OF SIGNIFICANCE: Many arthropods such as lobsters, crabs, stomatopods, isopods, and spiders have been the subject of research in recent years, and their hierarchical structure and mechanical properties extensively investigated. Yet, except for a limited number of pre-1980 publications, comparatively little work has been devoted to the terrestrial scorpion. The scorpion chela is a multifunctional part of the body (e.g. attack/defense, mating and protection from the environment) that involves the development of various stresses in the cuticle. How these stresses in the chela cuticle are managed by different chelae shape and size is still unknown. The lack of a single study that integrates morphological characterization of the entire hierarchical structure of the scorpion chela cuticle, and local mechanical properties, significantly affects the scientific knowledge regarding important structural approaches that can be used by nature to maximize functionality.


Cardiac allograft vasculopathy: a review.
Cardiac allograft vasculopathy (CAV) is a major factor limiting long-term survival after cardiac transplantation. CAV is an accelerated form of coronary artery disease (CAD) that is characterized by concentric fibrous intimal hyperplasia along the length of coronary vessels. Both immunologic and nonimmunologic risk factors contribute to the development of CAV by causing endothelial dysfunction and injury eventually leading to progressive intimal thickening. The diagnosis of CAV remains a challenge as angiography, the standard method for detecting focal plaques, lacks sensitivity in detecting CAV, and intravascular ultrasonography, a more sensitive method, lacks the ability to evaluate the entire coronary tree. The disease is difficult to treat and results in significant morbidity and mortality. Since treatment of CAV is limited and usually involves repeat transplantation, prevention or mitigation of immunologic and nonimmunologic risk factors is critically important. CAV prevention may involve therapy that provides protection against endothelial injury implemented just before transplantation, during storage and transplantation as well as after transplantation. This review addresses the frequency of occurrence, pathophysiology, diagnosis and treatment of CAV, highlighting areas of active research.


Abnormal configural face perception in a patient with right anterior temporal lobe atrophy.
Face perception is a vital aspect of human social functioning and involves specialized cognitive and neural mechanisms. For example, configural face processing involves determining the relationship between the parts of the face, and this process enables us to differentiate between different faces. Here, we report an unusual case in which right anterior temporal lobe atrophy resulted in a profound deficit in the ability to recognize faces. We demonstrate that this patient is not able to process faces via configural information, raising the possibility that the right anterior temporal lobe has a role in configural face processing.


Nutrients and degenerative eye diseases.
Cataract (opacity of the lens) and age-related degeneration of the macula of the retina are very common causes of disability in old age, and people are living longer. It seems likely that both of these conditions result from gradual photo-oxidative damage. The proteins in cataractous lenses are oxidized and 50 per cent of the fatty acids in membranes of retinal photo-receptors are highly polyunsaturated. The eye normally has unusually high concentrations of vitamin C and zinc which could have protective functions against free radical damage. For cataracts five reported case-control studies are reviewed and two prospective studies one of which included a very large number of subjects. Vitamin intakes were estimated from dietary histories or blood levels. In five of the six studies in which vitamin C was measured it appeared to be protective and vitamin E and carotenoids appeared protective in 5/7 studies. Other descriptive epidemiological studies are going on, including one in the Blue Mountains near Sydney. It is concluded that controlled trials of antioxidant nutrients for cataract prevention are now warranted. As to age-related muscular degeneration (ARMD), severe vitamin E deficiency is known to cause (a different type of) retinal degeneration spontaneously in humans (with cystic fibrosis or abetalipoproteinaemia) and experimentally in animals. Only three human case-control studies of ARMD and diet have been reported thus far and no clear relationship with any particular nutrient has emerged yet. Supplements containing antioxidant vitamins and zinc are being advertised and used in the USA and elsewhere but this is ahead of the evidence. More observational studies are needed and the US National Eye Institute is planning a 10 year intervention study, known as AREDS (Age-Related Eye Disease Study).


Pharmacological effects of serotonin reuptake inhibitors.
The effects of a series of tricyclic and non-tricyclic antidepressants on the transport of [3H]-serotonin into synaptosomal fractions from rat brain in vitro and in vivo are summarized. Differences in potency in vitro and in vivo would appear to be due partly to the presence of active metabolites, formed in vivo, that show different selectivities for the serotonin transport site. Evidence suggests that the initial reduction in serotonin turnover after acute administration of serotonin reuptake inhibitors is followed by a return to control values after the drug has been administered for at least 2 weeks. These changes in amine turnover are associated with normalization of both the serotonergic and beta-adrenergic receptor systems. Evidence suggests that changes in neurotransmitter receptor numbers and function of blood cells (platelets and lymphocytes) in depressed patients are possible state markers of the illness and that antidepressant efficacy may not be directly associated with specificity of amine reuptake inhibition. Studies also show that the bilaterally bulbectomized rat exhibits deficits in platelet and synaptosomal serotonin transport that resemble those shown in depressed patients. This animal model of depression may be useful not only for detecting putative antidepressants but also for studying the mode of action of such drugs during chronic administration.


The enthesis in psoriatic arthritis.
In recent years the argument that enthesitis is the primary lesion in many or most patients with psoriatic arthritis and spondyloarthritis has gained further credence from animal models including IL23/IL17 axis and TNF dependent models. The role of joint biomechanics at entheses and other sites of high physical stressing as a unifying underlying basis has also been strongly supported by animal models. Mirroring the animal model data, it has been empirically shown that therapies that work for entheseal-related inflammation in man including IL23/17 axis or TNF cytokine antagonism are effective for entheseal pathology. The biological basis for the effectiveness of other therapies including PDE4 inhibitors on enthesitis is poorly understood due to the relative difficultly in procurement of entheseal tissue. This absence of a histological gold standard renders it difficult to decipher how effective various therapies are in treatment of enthesitis. Despite advances in understanding enthesitis in animal models, there is a dearth of data thus far on the immunology of human entheses that likely will be key to further refinements in therapy development.


Novel technique for investigation and quantification of bacteriol leaching by Thiobacillus ferrooxidans.
A novel, efficient, and simple technique for the in situ study and quantification of the heterogeneous Bacteriol activity and the Bacteriol degradation of metal sulfides by Thiobacillus ferrooxidans is presented. It consists of exposing an ultrathin (300-2500 A) metal sulfide layer, FeS(2) in the experiments, to Thiobacillus f. grown in Touvinen media and visually following the Bacteriol attack and development of Bacteriol corrosion patterns under a light microscope. The uniform pyrite layer, partially transparent for visible light, permits the optical characterization of Bacteriol attack in remarkable detail. Several open or little understood questions concerning Bacteriol leaching, such as those on the kinetics of adhesion, the interfacial Bacteriol reproduction, the density of surface active bacteria, and the rate and morphology of sulfide degradation can also be studied. The degree of Bacteriol activity can be distinguished on the basis of development of variable sizes of spots and halos around Bacteriol cells produced by light passing through differently sized corrosion pits. The information obtained and identification of microorganisms has additionally been accentuated by immunofluorescence techniques (FA). It is concluded that the described method can be developed as a convenient testing and control technique for use in mine laboratories and bioleaching operations.


The lipid composition modulates the influence of the bovine seminal plasma protein PDC-109 on membrane stability.
The bovine seminal plasma protein PDC-109 exerts an essential influence on the sperm cell plasma membrane during capacitation. However, by any mechanism, it has to be ensured that this function of the protein on sperm cells is not initiated too early, that is, upon ejaculation when PDC-109 and sperm cells come into first contact, but rather at later stages of sperm genesis in the female genital tract. To answer the question of whether changes of the bovine sperm lipid composition can modulate the effect of PDC-109 on sperm membranes, we have investigated the influence of PDC-109 on the integrity of (i) differently composed lipid vesicles and of (ii) membranes from human red blood cells and bovine spermatozoa. PDC-109 most effectively disturbed lipid membranes composed of choline-containing phospholipids and in the absence of cholesterol. The impact of the protein on lipid vesicles was attenuated in the presence of cholesterol or of noncholine-containing phospholipids, such as phosphatidylethanolamine or phosphatidylserine. An extraction of cholesterol from lipid or biological membranes using methyl-beta-cyclodextrin caused an increased membrane perturbation by PDC-109. Our results argue for a oppositional effect of PDC-109 during sperm cell genesis. We hypothesize that the lipid composition of ejaculated bull sperm cells allows a binding of PDC-109 without leading to an impairment of the plasma membrane. At later stages of sperm cell genesis upon release of cholesterol from sperm membranes, PDC-109 triggers a destabilization of the cells.


OWL--a non-redundant composite protein sequence database.
A comprehensive, non-redundant composite protein sequence database is described. The database, OWL, is an amalgam of data from six publicly-available primary sources, and is generated using strict redundancy criteria. The database is updated monthly and its size has increased almost eight-fold in the last six years: the current version contains > 76,000 entries. For added flexibility, OWL is distributed with a tailor-made query language, together with a number of programs for database exploration, information retrieval and sequence analysis, which together form an integrated database and software resource for protein sequences.


Evaluation of the COBAS AMPLICOR MTB system.
A panel of 1,012 respiratory sediments was retrospectively tested by PCR amplification to detect Mycobacterium tuberculosis with the COBAS AMPLICOR MTB system. The sensitivities and specificities of COBAS and fluorescence microscopy compared to culture were 92.6 versus 95.6% and 99.6 versus 95.3%, respectively. Inhibition occurred in 48 (4.7%) specimens.


Prediction of Genetic Factors of Hyperthyroidism Based on Gene Interaction Network.
The number of hyperthyroidism patients is increasing these years. As a disease that can lead to cardiovascular disease, it brings great potential health risks to humans. Since hyperthyroidism can induce the occurrence of many diseases, studying its genetic factors will promote the early diagnosis and treatment of hyperthyroidism and its related diseases. Previous studies have used genome-wide association analysis (GWAS) to identify genes related to hyperthyroidism. However, these studies only identify significant sites related to the disease from a statistical point of view and ignore the complex regulation relationship between genes. In addition, mutation is not the only genetic factor of causing hyperthyroidism. Identifying hyperthyroidism-related genes from gene interactions would help researchers discover the disease mechanism. In this paper, we purposed a novel machine learning method for identifying hyperthyroidism-related genes based on gene interaction network. The method, which is called "RW-RVM," is a combination of Random Walk (RW) and Relevance Vector Machines (RVM). RW was implemented to encode the gene interaction network. The features of genes were the regulation relationship between genes and non-coding RNAs. Finally, multiple RVMs were applied to identify hyperthyroidism-related genes. The result of 10-cross validation shows that the area under the receiver operating characteristic curve (AUC) of our method reached 0.9, and area under the precision-recall curve (AUPR) was 0.87. Seventy-eight novel genes were found to be related to hyperthyroidism. We investigated two genes of these novel genes with existing literature, which proved the accuracy of our result and method.


Surfactant protein B deficiency and gene mutations for neonatal respiratory distress syndrome in China Han ethnic population.
To determine whether the SP-B deficiency and gene mutations in exon 4 is associated with neonatal RDS in China Han ethnic population. The study population consisted of 40 neonates with RDS and 40 neonates with other diseases as control in China Han ethnic population. We Compared SP-B expression in lung tissue and bronchoalveolar lavage fluid with immunoblotting, and analyzed mutations in the SP-B gene with polymerase chain reaction (PCR) and gene sequencing. In RDS group, low mature Surfactant protein B was found in both lung tissue and bronchoalveolar lavage fluid in 8 neonates. In control group, only 4 neonates with low mature Surfactant protein B in both lung tissue and bronchoalveolar lavage fluid. In RDS group, 20 neonates were found to have mutations in exon 4, 12 homozygous mutations with C/C genotype and 8 heterozygous mutations with C/T genotype in surfactant protein B gene+1580 polymorphism. There were 8 cases mutations in control group, 1 in C/C and 7 in C/T genotype. The frequency of homozygotes with C/C genotype was 0.3 and frequency of heterozygotes with C/T genotype was 0.02 in RDS group. In control group, frequency of homozygotes with C/C genotype was 0.025 and frequency of heterozygote with C/T genotype was 0.175. Low mature Surfactant protein B is associated with the pathogenesis of neonatal respiratory distress syndrome (RDS) in China Han ethnic population. Mutations in exon 4 of the surfactant protein B gene demonstrate an association between homozygous mutations with C/C genotype in SP-B gene and neonatal RDS.


Watch-and-wait approach for inactive echinococcal cysts: scoping review update since the issue of the WHO-IWGE Expert Consensus and current perspectives.
This work aims to provide an update of knowledge on the evolution of inactive cystic echinococcosis (CE) cysts (CE4-CE5) managed by 'watch-and-wait', by means of a scoping review of the literature published after the publication of the WHO-IWGE (Informal Working Group on Echinococcosis) Expert Consensus document in 2010. A total of 31 articles were included. Population ultrasound-based studies showed that spontaneously inactivated CE cysts represent 50.2% (95% confidence interval 38.7-61.8) of all detected untreated CE cysts, and that the prevalence of CE4-CE5 cysts tends to increase with age. Four longitudinal population-based studies showed that CE cysts naturally tend to evolve towards inactivation and that spontaneously inactivated cysts reactivate in a minority of cases. This was confirmed by four hospital-based studies, showing that spontaneously inactivated cysts reactivate rarely, while rate of reactivation is higher if inactivity was obtained posttreatment. It was not possible to drive conclusions on any difference in the clinical course of infection in immunocompromised or pregnant patients. CE cysts tend to evolve spontaneously to inactivation over time. The published literature supports the safety of the watch-and-wait approach for inactive cysts, sparing treatment to a substantial proportion of asymptomatic patients. A regular follow-up with ultrasound of all inactive cysts is required to detect reactivations.


Anti-angiogenic gene therapy for cancer (review).
Angiogenesis is a prerequisite for the growth and metastasis of solid tumors. Studies have confirmed that in the absence of angiogenesis, tumors rarely have the ability to develop beyond a few millimeters in diameter. Tumor-associated endothelium is activated by the production of soluble factors by tumor and stromal cells. Tumor-associated endothelial cells are physiologically homogeneous and divide more frequently. Thus, targeting the proliferation of tumor neovasculature will form an effective anti-cancer therapy. With the identification of drug and biological molecules that inhibit the growth of tumor endothelium, several attempts have been made in preclinical and clinical research to evaluate the potential of anti-angiogenic therapy. Although several drugs and purified proteins have shown promise, their wide-spread application is limited by half-life, side effects and cost involved. Gene therapy approaches, on the other hand, have the potential to overcome these limitations. Further, genetic transfer of anti-angiogenic genes can be combined with other treatments including radiation therapy or chemotherapy for synergistic effects. In this review, we provide a comprehensive account of factors and mechanisms underlying tumor angiogenesis, the potential and limitations of available gene therapy vectors for anti-angiogenesis and current status of preclinical and clinical gene therapy studies targeting tumor angiogenesis.


VAB-6 combination chemotherapy in disseminated cancer of the testis.
Twenty-nine men with stage III or unresectable stage II malignant germ cell tumors and no previous chemotherapy received treatments with the VAB-6 protocol. The VAB-6 regimen is a 1-year program beginning with three successive inductions at 3-to-4-week intervals: day 1--cyclophosphamide, 600 mg/m of body surface area intravenously, bleomycin, 30 mg intravenously, dactinomycin, 1 mg/m2 intravenously, and vinblastine, 4 mg/m2 intravenously; days 1 through 3--bleomycin, 20 mg/m2 . d by continuous infusion; and day 4--cisplatin, 120 mg/m2 intravenously. Bleomycin is omitted from the third induction. One month after the third induction, any residual disease is resected. If the resected specimen contains malignant tissue, an additional two inductions are given before maintenance with vinblastine, 6 mg/m2 intravenously, and dactinomycin, 1 mg/m2 intravenously, every 3 weeks. Of 25 patients with evaluable records, 23 achieved complete remission, and 21 remain in complete remission (median follow-up, more than 16 months). Myelosuppression is the major toxicity. With VAB-6 response rate is high, and treatment is short and better tolerated than with previous VAB protocols.


A non-immersive virtual reality-based intervention to enhance lower-extremity motor function and gait in patients with subacute cerebral infarction: A pilot randomized controlled trial with 1-year follow-up.
This study was conducted to evaluate whether a non-immersive virtual reality (VR)-based intervention can enhance lower extremity movement in patients with cerebral infarction and whether it has greater short-term and long-term effectiveness than conventional therapies (CTs). This was a single-blinded, randomized clinical controlled trial. Forty-four patients with subacute cerebral infarction were randomly allocated to the VR or CT group. All intervention sessions were delivered in the inpatient unit for 3 weeks. Outcomes were measured before (baseline) and after the interventions and at 3-month, 6-month and 1-year follow-ups. The outcomes included clinical assessments of movement and balance function using the Fugl-Meyer Assessment of Lower Extremity (FMA-LE) and Berg Balance Scale (BBS), and gait parameters in the sagittal plane. In the VR group, the walking speed after intervention, at 3-month, 6-month, and 1-year follow-ups were significantly greater than baseline (p = 0.01, <0.001, 0.007, and <0.001, respectively). Compared with baseline, BBS scores after intervention, at 3-month, 6-month, and 1-year follow-ups were significantly greater in both the VR group (p = 0.006, 0.002, <0.001, and <0.001, respectively) and CT group (p = <0.001, 0.002, 0.001, and <0.001, respectively), while FMA-LE scores after intervention, at 3-month, 6-month, and 1-year follow-ups were significant increased in the VR group (p = 0.03, <0.001, 0.003, and <0.001, respectively), and at 3-month, 6-month, and 1-year follow-ups in the CT group (p = 0.02, 0.004 and <0.001, respectively). In the VR group, the maximum knee joint angle in the sagittal plane enhanced significantly at 6-month follow-up from that at baseline (p = 0.04). The effectiveness of the non-immersive VR-based intervention in our study was observed after the intervention and at the follow-ups, but it was not significantly different from that of CTs. In sum, our results suggest that non-immersive VR-based interventions may thus be a valuable addition to conventional physical therapies to enhance treatment efficacy. http://www.chictr.org.cn/showproj.aspx?proj=10541, ChiCTR-IOC-15006064.


Synthetic peptide antagonists of glucagon.
Several glucagon analogs were synthesized in an effort to find derivatives that would bind with high affinity to the glucagon receptor of rat liver membranes but would not activate membrane-bound adenylate cyclase and, therefore, would serve as antagonists of the hormone. Measurements on a series of glucagon/secretin hybrids indicated that replacement of Asp9 in glucagon by Glu9, found in secretin, was the important sequence difference in the N terminus of the two hormones. Further deletion of His1 and introduction of a C-terminal amide resulted in des-His1-[Glu9]glucagon amide, which had a 40% binding affinity relative to that of native glucagon but caused no detectable adenylate cyclase activation in the rat liver membrane. This antagonist completely inhibited the effect of a concentration of glucagon that alone gave a full agonist response. It had an inhibition index of 12. The pA2 was 7.2. An attempt was made to relate conformation with receptor binding. The peptides were synthesized by solid-phase methods and purified to homogeneity by reverse-phase high-performance liquid chromatography on C18-silica columns.


Cascades of infant happiness: Infant positive affect predicts childhood IQ and adult educational attainment.
Parents want their children to be happy, educated, and successful, but are these goals related? People assume that success leads to happiness, but research on adults supports a reverse conceptualization: Happy people are more successful. Is happiness during childhood also linked to later success? Across the lifespan positive affect is linked with expanded cognitive abilities, learning, and resource building that can be adaptive and useful such that it leads to more success. Conversely, ongoing negative affect can reduce opportunities for growth and learning. Thus, happiness at any age may predict future success. Yet, no research has examined if positive and negative affect during infancy predicts childhood cognitive abilities and adult academics success. In a community sample, I hypothesized that higher infant positive affect (but not negative affect) would predict higher childhood cognitive abilities (i.e., IQ) and adult academic success (i.e., education attainment) in a 29-year study (n = 130). Positive affect, but not negative affect, during infancy (age 1.5), directly predicted higher childhood IQ (ages 6-8) and higher educational attainment (age 29), even after controlling for family socioeconomic status and infant intelligence. Childhood IQ partially explained the link between positive affect during infancy and adult educational attainment. This study advances understanding of how happiness during infancy (before formal education has begun) is linked to gold standard indicators of cognitive abilities and adult academic success. Parents, educators, and policymakers may want to place a higher value on early affective experiences when considering educational success. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Sequential organ failure assessment score predicts mortality after coronary artery bypass grafting.
Mortality after coronary artery bypass grafting (CABG) is generally associated with underlying disease and surgical factors overlooked in preoperative prognostic models. Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE II) scores are widely used in intensive care units for outcome prediction. This study investigated the accuracy of these models in predicting mortality. Between January 2010 and April 2013, 483 patients who underwent isolated CABG were enrolled. The clinical characteristics, outcomes, and prognostic model scores of the patients were collected. Discrimination was assessed using the area under the curve approach. Both SOFA and APACHE II scores were effective for predicting in-hospital mortality. Among the organ systems examined in the SOFA, the cardiac and renal systems were the strongest predictors of CABG mortality. Multivariate analysis identified only the SOFA score as being an independent risk factor for mortality. In summary, the SOFA score can be used to accurately identify mortality after isolated CABG.


Selective photoinactivation of Histoplasma capsulatum by water-soluble derivatives chalcones.
Histoplasmosis is a respiratory and systemic disease caused by the dimorphic fungus Histoplasma capsulatum. The clinical features may vary from asymptomatic infections to disseminated severe form depending of patient immunity. The treatment of histoplasmosis can be performed with itraconazole, fluconazole, and in the disseminated forms is used amphotericin B. However, the critical side effects of amphotericin B, the cases of itraconazole therapy failure and the appearance of fluconozole-resistant strains makes necessary the search of new strategies to treat this disease. Antimicrobial photodynamic therapy (aPDT) seems to be a potential candidate once have been show efficacy to inhibit others dimorphic fungi. Although the photosensitizer (PS) chalcone aggregates in biological medium, it has antifungal activity and show a high quantum yield of ROS formation. So, the aim of this study was to obtain the experimental parameters to achieve an acceptable selective chalcone water-soluble derivatives photoinactivation of H. capsulatum comparing with fibroblastic and keratinocytes cells which are the constituents of some potential host tissues. Yeast and cells were incubated with the same chalchones concentrations and short incubation time followed by irradiation with equal dose of light. The best conditions to kill H. capsulatum selectively were very low photosensitizers concentration (1.95μgmL-1) incubated by 15min and irradiated with LED 450nm with 24Jcm-2. Key words: chalcone, Histoplasma capsulatum, aPDT, selectivity.


Is it possible to 3D bioprint load-bearing bone implants? A critical review.
Rehabilitative capabilities of any tissue engineered scaffold rely primarily on the triad of (i) biomechanical properties such as mechanical properties and architecture, (ii) chemical behavior such as regulation of cytokine expression, and (iii) cellular response modulation (including their recruitment and differentiation). The closer the implant can mimic the native tissue, the better it can rehabilitate the damage therein. Among the available fabrication techniques, only 3D bioprinting (3DBP) can satisfactorily replicate the inherent heterogeneity of the host tissue. However, 3DBP scaffolds typically suffer from poor mechanical properties, thereby, driving the increased research interest in development of load-bearing 3DBP orthopedic scaffolds in recent years. Typically, these scaffolds involve multi-material 3D printing, comprising of at-least one bioink and a load-bearing ink; such that mechanical and biological requirements of the biomaterials are decoupled. Ensuring high cellular survivability and good mechanical properties are of key concerns in all these studies. 3DBP of such scaffolds is in early developmental stages, and research data from only a handful of preliminary animal studies are available, owing to limitations in print-capabilities and restrictive materials library. This article presents a topically focused review of the state-of-the-art, while highlighting aspects like available 3DBP techniques; biomaterials' printability; mechanical and degradation behavior; and their overall bone-tissue rehabilitative efficacy. This collection amalgamates and critically analyses the research aimed at 3DBP of load-bearing scaffolds for fulfilling demands of personalized-medicine. We highlight the recent-advances in 3DBP techniques employing thermoplastics and phosphate-cements for load-bearing applications. Finally, we provide an outlook for possible future perspectives of 3DBP for load-bearing orthopedic applications. Overall, the article creates ample foundation for future research, as it gathers the latest and ongoing research that scientists could utilize.


Synergies analysis produces consistent results between motion analysis laboratories.
The dynamic motor control index during walking (walk-DMC) is a scaled measure of motor control derived from electromyographic analysis of the lower extremity during gait. Walk-DMC has been shown to be related to patient outcomes and there has been an increasing interest from motion analysis centers regarding using this metric in their own practice. However, the methods for computing the index reported in the literature are not consistent. Here we propose a standardized method and investigate if this leads to results that are consistent between laboratories. Comparisons between three sets of typically developing controls contributed by three independent motion analysis centers are made. Comparisons are also made between the proposed and previously published methods. A program script to compute the walk-DMC was used for this study and is made freely available with this manuscript. Using this script, results are highly consistent between three participating centers. The currently proposed method results in a wider distribution of walk-DMC values than those previously reported. Using consistent processing methods, synergy measures are equivalent between centers. The major differences between current and published data are attributed to the use of concatenation of several walking trials.


[Fibroma of the tendon sheath. Diagnosis and differential diagnosis].
Ten cases of fibroma of the tendon sheath were examined by means of histological, topochemical, and immunohistochemical methods. Investigations were aimed at re-evaluation of histological variability and definition of diagnostic criteria. Microscopic observations suggested the following features to be typical of fibroma of the tendon sheath: Primitive mesenchymal or fibroblastic cells without further differentiation, slit- and cleft-like spaces with lining cells decorated by endothelial markers, and collagenous, cartilaginous or myxoid basic substance at least in areas rich with sulphated glycosaminoglycans. Differential diagnostic distinction of tendon sheath fibroma from myxoid cartilage tumors, fasciitis nodularis, and myxoid fibromatosis as well as from fibrohistiocytic lesions and giant cell tumors of tendon sheath is discussed with reference to the above definition.


Effects of dichloroacetate on myocardial substrate extraction, epicardial ST-segment elevation, and ventricular blood flow following coronary occlusion in dogs.
Glucose metabolism in the healthy heart is stimulated by dichloroacetate (DCA). The possibility has been examined in dogs that DCA, by increasing glucose utilization, might limit the severity of acute myocardial ischaemic injury. Intravenous administration of DCA reduced the degree of epicardial ST-segment elevation induced by subsequent coronary occlusion, both under basal conditions and during isoprenaline infusion. A similar result was obtained when DCA was given during an established coronary occlusion. This effect could not be explained by changes in mean aortic blood pressure, heart rate, or regional myocardial blood flow as measured by radioactive microspheres. Measurements in arterial and coronary sinus blood demonstrated an increase in the extraction of glucose and a decrease in that of FFA by the heart. Glucose extraction also tended to be increased in the ischaemic zone, as shown by the differences in the concentrations of these substrates between arterial blood and blood obtained from the local vein draining that zone. Lactate release by the ischaemic zone was markedly reduced.


[Mitogenic and mutagenic effects of ionized air on Allium fistulosum L].
In the apical meristem of Allium fistulosum, the relationship between peroxide lipid oxidation, antioxidant activity, proliferative processes, the yield of chromosomal aberrations and duration the exposure to ionized air was studied. Under the influence of air oxygen ions, superoxide dismutase and catalase activities increased, proliferative processes were stimulated, and shifts occurred in the process of lipid peroxidation in cells of A. fistulosum. When these cells were treated with air oxygen for 40 min, hydrogen peroxide and iron sulfate (II) enhanced oxygen biostimulating effect via stimulation of antioxidant enzyme activity and inhibition of lipid peroxidation. Under these conditions, cell proliferation was intensified and the yield of chromosomal aberrations was reduced in A. fistulosum rootlets. When the time of seed treatment with ionized air was increased to 80 min, lipid peroxidation was activated, antioxidant enzyme activity was inhibited, and the yield of chromosomal aberration increased in seedlings. It was concluded that the biostimulating activity of ionized air was mediated by active oxygen species generated in the cell. The accumulation of TBA(thiobarbituric acid)-reactive products was shown to be related to a decrease in antioxidant enzyme activity and an increase in the yield of chromosomal aberrations. It is emphasized that the mutagenic effect of ionized air is associated with generating conditions that support Fenton reaction and OH-radical formation in the cell.


Electro- and opto-mutable properties of MgO nanoclusters adsorbed on mono- and double-layer graphene.
Inspired by recent experiments, the trapping of molecules in 2D materials has gained increasing attention due to the unique ability of the molecules to modulate the electronic and optical properties of 2D materials, which calls for fundamental understanding and predictive design strategies. Herein, we focus on mono- and double-layer graphene encapsulating various MgO clusters and explore their diverse electronic and optical properties using a number of high-level first-principles calculations. By correlating the stability of adsorption, geometry, charge transfer, band structures, optical absorption spectrum, and the van der Waals pressure, our results decode various synergies in electro- and opto-mutable properties of MgO/graphene systems. We found that 2D-MgO flakes on graphene layers exhibit surface polarization effects - in contrast to their isolated neutral flakes - and show a significant charge transfer from graphene to n-doped flakes, breaking the symmetry of graphene layers. We obtained a van der Waals pressure of ∼0.7 (0.9) GPa on bilayer graphene encapsulating MgO nanoclusters, which matches extremely well with experiment. While there is one quantum emission in the visible light region for a single MgO flake, a wide range of visible light is accessible for MgO on mono- and double-layer graphene. Overall, these findings provide new physical insights and design strategies to modulate 2D materials with several applications in optoelectronics while significantly broadening the spectrum of strategies for fabricating new hybrid 2D heterostructures by encapsulating external molecules.


Upregulation of Mitf by Phenolic Compounds-Rich Cymbopogon schoenanthus Treatment Promotes Melanogenesis in B16 Melanoma Cells and Human Epidermal Melanocytes.
Melanin provides inherent protection against skin cancer by absorbing broad-spectrum radiant energy of UV radiation. Cutaneous malignant melanoma incidence has recently been observed to increase and the frequency is closely associated with the skin color, highlighting the importance of skin pigmentation. Here, we showed how melanin biosynthesis is enhanced by treatment with phenolic compounds-rich Cymbopogon schoenanthus (CYM) in B16 murine melanoma cells and human epidermal melanocytes (HEM). CYM increased the melanin content of the cells by upregulating the expression of tyrosinase (TYR), tyrosinase-related protein 1 (TRP1), and dopachrome tautomerase (DCT) at the protein and mRNA levels, comparable to the effect of α-melanocyte-stimulating hormone (MSH), in both B16 cells and HEM. Moreover, global gene expression analysis showed that at least 44 pigmentation-associated genes were modulated, including the microphthalmia-associated transcription factor (Mitf) and its transcriptional regulators (Sox10, Pax3, and Lef1). Upregulation of copper transport-associated gene Atp7b indicates that CYM also promotes tyrosinase activity. CYM upregulated Mitf and possibly activates tyrosinase enzyme, providing evidence for its possible use to promote melanogenesis and as a therapeutic agent against hypopigmentation disorders.


Performance of plastic electron optics components fabricated using a 3D printer.
We show images produced by an electron beam deflector, a quadrupole lens and a einzel lens fabricated from conducting and non-conducting plastic using a 3D printer. Despite the difficulties associated with the use of plastics in vacuum, such as outgassing, poor conductivity, and print defects, the devices were used successfully in vacuum to steer, stretch and focus electron beams to millimeter diameters. Simulations indicate that much smaller focus spot sizes might be possible for such 3D-printed plastic electron lenses taking into account some possible surface defects. This work was motivated by our need to place electron optical components in difficult-to-access geometries. Our proof-of-principle demonstration opens the door to consider 3D-printed electron microscopes, whose reduced cost would make such microscopes more widely available. Potentially, this may have a significant impact on electron beam science and technology in general and electron microscopy in particular.