The mediation effect of self-esteem on job-burnout and self-efficacy of special education teachers in Western China.
Teacher self-efficacy may reduce the likelihood of burnout through preventing the occurrence of work stress. The study inquiries the relationship between teaching efficacy and burnout, focus on mediation of self-esteem. A sample of 329 Chinese special teachers who teach in the special schools in western China was measured with the Maslach Burnout Inventory, the Rosenberg self-esteem scale and the Self-efficacy scale. Results indicated that emotional exhaustion and depersonalization of Chinese special teachers are at a medium level and personal accomplishment are at a low level. The mediation analysis shows that under the education background of special education, self-esteem plays partial mediation role in general teaching efficacy or personal teaching efficacy and job burnout of special education teachers.


A new ELISA for the three-spined stickleback (Gasterosteus aculeatus L.) spiggin, using antibodies against synthetic peptide.
The aim of this study was to develop an enzyme-linked immunosorbent (ELISA) assay to quantify spiggin in the three-spined stickleback. Spiggin is a glue protein produced in the kidney of male three-spined stickleback under the control of androgens during the breeding period. Disturbances of spiggin production in male fish and abnormal induction of spiggin in female fish are considered as valuable biomarkers of exposure to (anti-)androgenic chemicals. Polyclonal antibodies against a peptide sequence of spiggin (HRD-16) were used and the specificity of the antibodies was verified by Western blotting and direct ELISA experiments. By using HRD-16 antibodies and spiggin standard preparation, a competitive ELISA was set-up and validated. This assay appears sensitive, with a detection limit of 0.5 U/mL, and specific, as shown by the competition curves, obtained by serial dilution of male and female kidney homogenates, that were parallel to the spiggin standard curves. The ability of the spiggin ELISA to quantify spiggin induction was achieved by exposing male and female three-spined sticklebacks to 0.1 and 1 microg/L of methyltestosterone. The results show a significant dose-dependent induction of spiggin in methyltestosterone-exposed female fish compared to controls.


[Diversities in the treatment of patients with chronic obstructive lung disease].
Bronchial asthma and chronic obstructive lung disease are characterised by dyspnoea, cough and, during exacerbation, wheeze in some patients. The common pathophysiological element is obturation of the bronchial tree and chronic inflammation. These diseases differ, however, in location of the inflammatory process in the respiratory system, various degree of participation of inflammatory cells and inflammation mediators. These elements influence the effectiveness of treatment. In both diseases inhalant and systemic glucocorticosteroids, beta 2-mimetics, cholinolytics, theophylline. The reaction to these drugs is, however, different. In the paper, differences in treatment of these diseases are also discussed.


Relationship between physical and conceptual color codes.
The experiment was designed to determine whether the efficacy of the conceptual color code increases as the availability of the physical color code decreases. On each trial subjects judged whether two color chips were physically identical. On primed trials the prototype color chip was presented for 2 s prior to the test pair. After exposure to test pairs involving moderate goodness levels, all subjects responded to test pairs consisting of either good or poor members of a category. For some subjects the test pairs were presented immediately after the termination of the prototype chip. For other subjects there was either a 1- or 2-s delay between viewing the prototype chip and the presentation of the test pair. Under delay conditions of both 0 s and 1 s, priming with the prototype chip facilitated responses to good members of the category and inhibited responses to poor members of the category. However, after a 2-s delay, priming facilitated responses to both good and poor category members. It was argued that under the 0- and 1-s conditions priming effects were mediated by the physical color code. When the availability of the physical code was reduced by the 2-s delay, priming effects were determined by the modified conceptual representation.


Immunoregulatory T cells in males vulnerable to Epstein-Barr virus with the X-linked lymphoproliferative syndrome.
The X-linked lymphoproliferative syndrome (XLP) is a primary immune deficiency. Affected males are vulnerable to fatal infection by Epstein-Barr virus (EBV). In patients who had survived an infection by EBV, helper and cytotoxic T cells reactive to virus-transformed autologous B lymphoblastoid cells were infrequent. This was similar to that observed in normal individuals seronegative to EBV. In contrast, frequencies of the reactive T cells were high in normal controls seropositive to EBV. Patients with XLP also had a propensity to activate radiosensitive suppressor cells when their T cells were stimulated by EBV transformed B cells. Hence, clonal expansion of helper and cytotoxic T cells to virus-transformed B cells failed to occur during an EBV infection in these patients because of immunosuppression. These defects in the T cell repertoire of patients with XLP may predispose them to be susceptible to EBV-induced lymphoproliferation and contribute to the variability in expression of the phenotypes seen in these patients.


Oral health status in an adult Swedish population. Prevalence of caries. A cross-sectional epidemiological study in the Northern Alvsborg county.
The aim of the present epidemiological study was to describe prevalence, distribution and type of caries in an adult Swedish population. After stratification with respect to age (20-29, 30-39,.....greater than 79 years of age), sex and location of residence (city, village, rural region), a random sample of 967 individuals was drawn (0.75% of the total adult population greater than 19 years). The results were based on radiographic and clinical examination of 919 individuals, of whom 750 were dentate (participation rate: 95%). The examinations were carried out from November 1983 to December 1984. The caries registrations distinguished between enamel caries and root caries, subdivided into manifest and initial caries. Despite lower number of remaining teeth in older ages, the mean number of surfaces with manifest caries (DS) was relatively even in all age groups (4.1-5.1 DS), except for the youngest age group ("20-29 years": mean 3.1 DS). When the number of decayed teeth (DT) were expressed as a percentage of remaining teeth, the ratio (%) was markedly higher in the older age groups than in the younger age groups. Initial caries was more frequent in the younger age groups. In the age groups above forty years the majority of the observed carious lesions involved root surfaces. In the oldest age group ("greater than 79 years of age"), 95% of the lesions were root caries. The mean number of filled surfaces (FS) was higher among women than men, while untreated caries (DS) showed a tendency of higher values for men. No significant differences in caries prevalence related to location of residence could be demonstrated.


Tobacco use and cardiovascular disease among American Indians: the strong heart study.
Tobacco use among American Indians has a long and complicated history ranging from its utilization in spiritual ceremonies to its importance as an economic factor for survival. Despite this cultural tradition and long history, there are few studies of the health effects of tobacco in this population. The Strong Heart Study is a prospective observational study of cardiovascular disease (CVD) in 13 American Indian tribes in Arizona, Oklahoma, and North and South Dakota with 4,549 participants. Baseline examinations were followed by two examinations at regular intervals and 16 years of morbidity and mortality follow-up. Hazard ratios (HRs) for non-fatal CVD for current smokers vs. non-smokers after adjusting for other risk factors were significant in women (HR = 1.94, 95% CI 1.54 to 2.45) and men (HR = 1.59, 95% CI 1.16 to 2.18). Hazard ratios for fatal CVD for current smokers vs. non-smokers after adjusting for other risk factors were significant in women (HR = 1.64, 95% CI 1.04 to 2.58), but not in men. Individuals who smoked and who were diagnosed with diabetes mellitus, hypertension or renal insufficiency were more likely to quit smoking than those without these conditions. On average, American Indians smoke fewer cigarettes per day than other racial/ethnic groups; nevertheless, the ill effects of habitual tobacco use are evident in this population.


High c-myc amplification level contributes to the tumorigenic phenotype of the human breast carcinoma cell line SW 613-S.
The c-myc gene is amplified in the SW 613-S cell line which was established from a human breast carcinoma. This line is heterogeneous: it contains cells with a high level of amplification and carrying the extra copies of the c-myc gene in double minute chromosomes (DMs) and cells with few c-myc genes integrated into chromosomes. Clones with different levels of amplification and different cytological localization of the c-myc copies were isolated from the SW 613-S cell population. Those with a high level of amplification and expression of the c-myc gene were highly tumorigenic in nude mice whereas those with a low level were not. Introduction of c-myc gene copies by transfection into the cells of several non-tumorigenic clones restored the tumorigenic phenotype. Our results indicate that a high level of amplification of the c-myc gene is a requirement for the tumorigenicity of SW 613-S cells in animals.


Transpleural Ventilation via Spiracles in Severe Emphysema Increases Alveolar Ventilation.
In emphysema airway resistance can exceed collateral airflow resistance, causing air to flow preferentially through collateral pathways. In severe emphysema ventilation through openings directly through the chest wall into the parenchyma (spiracles) could bypass airway obstruction and increase alveolar ventilation via transpleural expiration. During lung transplant operations, spiracles occasionally can occur inadvertently. We observed transpleural expiration via spiracles in three subjects undergoing lung transplant for emphysema. During transpleural spiracle ventilation, inspiratory tidal volumes (TV) were unchanged; however, expiration was entirely transpleural in two patients whereas the expired TV to the ventilator circuit was reduced to 25% of the inspired TV in one. At baseline, mean PCO2 was 61 ± 5 mm Hg, which decreased to a mean PCO2 of 49 ± 5 mm Hg (P = .05) within minutes after transpleural spiracle ventilation and further decreased at 1 to 2 h (36 ± 4 mm Hg; P = .002 compared with baseline) on unchanged ventilator settings. This observation of increased alveolar ventilation supports further studies of spiracles as a possible therapy for advanced emphysema.


Peganum Harmala (Aspand) Intoxication; a Case Report.
There are several reports in the literature indicating a great variety of pharmacological effects for peganum harmala or aspand such as sedative anti-bacterial, anti-fungal, antiviral and antiprotozoal. Some people believe that can be used for treatment of some organic or psychiatric disorders. We introduce a woman with history of long time constipation that was disappointed in novel medical treatment and decided to use comminuted Aspand to relieve her problem. Two hours after use, the intoxication symptoms manifested as blurred vision, phonophobia, floating feeling, and tinnitus ringing. Here we report the treatment process and outcome of this case.


A genetically attenuated malaria vaccine candidate based on P. falciparum b9/slarp gene-deficient sporozoites.
A highly efficacious pre-erythrocytic stage vaccine would be an important tool for the control and elimination of malaria but is currently unavailable. High-level protection in humans can be achieved by experimental immunization with Plasmodium falciparum sporozoites attenuated by radiation or under anti-malarial drug coverage. Immunization with genetically attenuated parasites (GAP) would be an attractive alternative approach. In this study, we present data on safety and protective efficacy using sporozoites with deletions of two genes, that is the newly identified b9 and slarp, which govern independent and critical processes for successful liver-stage development. In the rodent malaria model, PbΔb9ΔslarpGAP was completely attenuated showing no breakthrough infections while efficiently inducing high-level protection. The human PfΔb9ΔslarpGAP generated without drug resistance markers were infective to human hepatocytes in vitro and to humanized mice engrafted with human hepatocytes in vivo but completely aborted development after infection. These findings support the clinical development of a PfΔb9ΔslarpSPZ vaccine.


[Retroperitoneal non-secreting paraganglioma].
Paraganglioma is a rare tumor arising from indifferentiated cells of the primitive neural crest. These tumors are most commonly found in the adrenal gland but other localisations are possible. We described a 60-year-old men with a right retro-peritoneal mass discovered on ultrasound examination. This tumor had an heterogeneous appearance on i.v. contrast injected CT (computed tomography) and MR (magnetic resonance) images. Plasma and urinary catecholamines were normal. This tumor was surgically removed. Immunohistochemical analyses revealed that the tumor cells were strongly positive for neurone specific enolase and chromogranin A. Histopathologic examination diagnosed a non secreting paraganglioma in the right retroperitoneum. After surgery, the patient remained asymptomatic without treatment.


[Hypothyroxinemia in the low birth-weight infant in the screening of congenital hypothyroidism].
Inside a pilot screening program for Congenital Hypothyroidism, T4 and TSH have been tested in sick and healty preteam and fullterm low birth weight (LBW) newborns during the first two months of life, 36 newborns affected by respiratory distress syndrome and 15 by sepsis have been included in the study. Blood samples were collected by heel puncture on 3rd, 10th, 20th, 40th and, in some cases, up to 60th day of life, and adsorbed on filter paper. Our findings show that hypothyroxinaemia in LBW newborns is strictly related to gestational age. In fact, among preterm infants with GA less than or equal to 33 weeks, 25 subjects (69,44%) showed T4 levels less than or equal to 6 micrograms/dl and 5 infants (13,88%) had T4 concentrations less than or equal to 2 micrograms/dl. The incidence of subjects with T4 values less than or equal to 6 micrograms/dl falls to 42,18% in the group of infants with GA = 34-36 weeks and to 17,27% in the group of fullterm LBW infants. None of these newborns showed thyroxine levels less than or equal to 2 micrograms/dl. All the examined infants showed normal TSH levels. The low T4 values may appear soon after birth or later (3rd-20th day of life) and sometimes persist up to 40th or 60th day, despite of always normal TSH levels. The mean of low T4 values at each sampling time is strictly and directly related to gestational age. (ABSTRACT TRUNCATED AT 250 WORDS)


Reduced microtubule acetylation in cystic fibrosis epithelial cells.
Dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) leads to many cellular consequences, including perinuclear accumulation of free cholesterol due to impaired endosomal transport. The hypothesis being tested is that CF-related perinuclear cholesterol accumulation due to disrupted endocytic trafficking occurs as a result of reduced microtubule (MT) acetylation. Here, it is identified that acetylated-α-tubulin (Ac-tub) content is reduced by ∼40% compared with respective wild-type controls in both cultured CF cell models (IB3) and primary Cftr-/- mouse nasal epithelial tissue. Histone deacetylase 6 (HDAC6) has been shown to regulate MT acetylation, which provides reasonable grounds to test its impact on reduced Ac-tub content on CF cellular phenotypes. Inhibition of HDAC6, either through tubastatin treatment or HDAC6 knockdown in CF cells, increases Ac-tub content and results in redistributed free cholesterol and reduced stimulation of NF-κB activity. Mechanistically, endoplasmic reticulum stress, which is widely reported in CF and leads to aggresome formation, is identified as a regulator of MT acetylation. F508del CFTR correction with C18 in primary airway epithelial cells restores MT acetylation and cholesterol transport. A significant role for phosphatidyl inositol-3 kinase p110α is also identified as a regulator of MT acetylation.


High glucose inhibits vascular endothelial Keap1/Nrf2/ARE signal pathway via downregulation of monomethyltransferase SET8 expression.
Hyperglycemia-mediated reactive oxygen species (ROS) accumulation plays an important role in hyperglycemia-induced endothelial injury. Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway inhibition participates in hyperglycemia-induced ROS accumulation. Our previous study indicated that SET8 overexpression inhibits high glucose-mediated ROS accumulation in human umbilical vein endothelial cells (HUVECs). In the present study, we hypothesize that SET8 may play a major role in high glucose-induced ROS accumulation via modulation of Keap1/Nrf2/ARE pathway. Our data indicated that high glucose mediated cell viability reduction, ROS accumulation, and Nrf2/ARE signal pathway inhibition via upregulation of Keap1 expression in HUVECs. Moreover, high glucose inhibited the expressions of SET8 and H4K20me1 (a downstream target of SET8). SET8 overexpression improved high glucose-mediated Keap1/Nrf2/ARE pathway inhibition and endothelial oxidation. Consistently, the effects of sh-SET8 were similar to that of high glucose treatment and were reversed by si-Keap1. A mechanistic study found that H4K20me1 was enriched at the Keap1 promoter region. SET8 overexpression attenuated Keap1 promoter activity and its expression, while mutant SET8 R259G did not affect Keap1 promoter activity and expression. The results of this study demonstrated that SET8 negatively regulates Keap1 expression, thus participating in high glucose-mediated Nrf2/ARE signal pathway inhibition and oxidative injury in HUVECs.


Structural and biochemical insights into the DNA-binding mode of MjSpt4p:Spt5 complex at the exit tunnel of RNAPII.
Spt5 (NusG in bacteria) is the only RNA polymerase-associated factor known to be conserved in all three domains of life. In archaea and eukaryotes, Spt5 associates with Spt4, an elongation factor that is absent in bacteria, to form a functional heterodimeric complex. Previous studies suggest that the Spt4:Spt5 complex interacts directly with DNA at the double-stranded DNA exit tunnel of RNA polymerase to regulate gene transcription. In this study, the DNA-binding ability of Spt4:Spt5 from the archaeon Methanocaldococcus jannaschii was confirmed via nuclear magnetic resonance chemical shift perturbation and fluorescence polarization assays. Crystallographic analysis of the full-length MjSpt4:Spt5 revealed two distinct conformations of the C-terminal KOW domain of Spt5. A similar alkaline region was found on the Spt4:Spt5 surface in both crystal forms, and identified as double-stranded DNA binding patch through mutagenesis-fluorescence polarization assays. Based on these structural and biochemical data, the Spt4:Spt5-DNA binding model was built for the first time.


Headspace solid-phase microextraction with 1-pyrenyldiazomethane on-fibre derivatisation for analysis of fluoroacetic acid in biological samples.
A new and in part automated headspace solid-phase microextraction method for quantitative determination of the highly toxic rodenticide fluoroacetic acid (FAA) in serum and other biological samples has been developed. FAA and deuterated acetic acid (internal standard) were extracted from acidified samples by a StableFlex divinylbenzene-Carboxen on polydimethylsiloxane fibre. The acids were derivatised on the fibre in-situ with 1-pyrenyldiazomethane and detected using gas chromatography-mass spectrometry with electron impact ionisation and selected ion monitoring. The calibration curve for FAA in serum was linear over the range from 0.02 to 5 microg/ml, with limits of detection and quantification of 0.02 and 0.07 microg/ml, respectively. The method was also tested with spiked whole blood, urine, stomach contents and kidney samples. It was sufficiently reliable, reproducible and sensitive for use in routine forensic toxicology applications.


Phytochemicals in Skin Cancer Prevention and Treatment: An Updated Review.
Skin is the largest human organ, our protection against various environmental assaults and noxious agents. Accumulation of these stress events may lead to the formation of skin cancers, including both melanoma and non-melanoma skin cancers. Although modern targeted therapies have ameliorated the management of cutaneous malignancies, a safer, more affordable, and more effective strategy for chemoprevention and treatment is clearly needed for the improvement of skin cancer care. Phytochemicals are biologically active compounds derived from plants and herbal products. These agents appear to be beneficial in the battle against cancer as they exert anti-carcinogenic effects and are widely available, highly tolerated, and cost-effective. Evidence has indicated that the anti-carcinogenic properties of phytochemicals are due to their anti-oxidative, anti-inflammatory, anti-proliferative, and anti-angiogenic effects. In this review, we discuss the preventive potential, therapeutic effects, bioavailability, and structure-activity relationship of these selected phytochemicals for the management of skin cancers. The knowledge compiled here will provide clues for future investigations on novel oncostatic phytochemicals and additional anti-skin cancer mechanisms.


Microdisplacement printing.
We describe a new patterning technique that employs microcontact printing to replace preformed labile self-assembled monolayers (SAMs) selectively; we call this "microdisplacement printing". We demonstrate that this technique results in ordered molecular regions of both the patterning ("displacing") molecule as well as the remnant labile film, here 1-adamantanethiolate. The existence of the 1-adamantanethiolate SAM before patterning hinders lateral surface diffusion of the patterning molecules, and therefore permits the use of molecules that are otherwise too mobile to pattern by other methods.


Therapeutic Mastoidectomy in the Management of Noncholesteatomatous Chronic Otitis Media: Literature Review and Cost Analysis.
Despite evidence that therapeutic mastoidectomy does not improve outcomes in noncholesteatomatous chronic otitis media, it remains widely performed. An up-to-date systematic review is undertaken and conclusions drawn regarding the best evidence-based practice of its management. PubMed, Google Scholar, Medline Embase, Cochrane, and Web of Science. A combination of the following words was used: chronic otitis media, chronic suppurative otitis media, COM, CSOM, mastoidectomy, tympanoplasty, atelectasis, retraction, tympanic perforation, and therapeutic. From 1742 studies, 7 were selected for full analysis with respect to the benefit of mastoidectomy in the management of active and inactive mucosal chronic otitis media. Most were retrospective studies, with 1 prospective randomized controlled trial available. Overall, there was no evidence to support routine mastoidectomy in conjunction with tympanoplasty in chronic otitis media. For ears with sclerotic mastoids, the evidence suggested that there may be some benefit as a staged procedure. Two studies were analyzed for the benefit of mastoidectomy in addition to tympanoplasty for the management of the atelectatic ear (inactive squamous chronic otitis media). The conclusion was also that mastoidectomy added no benefit. Examination of the available literature supports the notion that therapeutic mastoidectomy does not lend any additional benefit to the management of noncholesteatomatous chronic otitis media. This has implications for patient care, both clinically and financially. Further research, ideally in the form of a prospective, multi-institutional, geographically wide, ethnically diverse, randomized controlled trial, is needed to further support this notion.


Validity of certification measures for occupational therapists.
Major factors that can affect the results of validation studies are identified and include reliability, homogeneity of sample, and criterion contamination. An overview and a description of content, predictive, concurrent, and construct validities are presented as well as a review of the recent studies of the validity of the Field Work Performance Report and the Certification Examination for Occupational Therapists. Adequate evidence of content and concurrent validity has been established for the Field Work Performance Report, although evidence for long-range predictive validity is lacking. Content validity alone has been established for the Certification Examination for Occupational Therapists. The evidence indicates that the instruments should not be abandoned, that they are better than no measures at all. The directions research might take in the future are given and the implications of continued use of the instruments are evaluated.


Early precursor thymocytes can produce interleukin 2 upon stimulation with calcium ionophore and phorbol ester.
T-cell precursors were stimulated with a conventional T-cell mitogen or with the calcium ionophore A23187 in order to determine whether pre-T cells acquire the ability to produce interleukin 2 (IL-2) before they acquire the ability to respond to antigen or mitogenic lectins. Immature T cells were obtained by eliminating mouse thymocytes that expressed the Lyt2 and L3T4 cell surface proteins. The remaining Lyt2-, L3T4- cells were stimulated for IL-2 production by using concanavalin A (Con A) or A23187, together with phorbol 12-myristate 13-acetate (PMA). We found that these "double-negative" thymocytes were unresponsive to Con A plus PMA but produced substantial amounts of IL-2 when stimulated with A23187 plus PMA. In contrast, both stimulation regimens induced more mature T-lymphocyte populations to produce IL-2. This implies that developing T cells acquire the ability to make IL-2 upon induction before they acquire the ability to be triggered by Con A. Day-15 fetal and cortical thymocytes were also tested for their ability to make IL-2. Both populations failed to synthesize this growth factor, even when stimulated with A23187 and PMA. For cortical thymocytes, this result, together with the finding that A23187 plus PMA fails to activate these cells, suggests that this population is immunologically inert rather than immature. On the other hand, the inability of day-15 fetal thymocytes to produce IL-2 indicates that these T-cell precursors are developmentally distinct from adult Lyt2-, L3T4- thymocytes, which they phenotypically resemble.


High moisture extrusion of lupin protein: influence of extrusion parameters on extruder responses and product properties.
High moisture extrusion (HME) of lupin protein concentrate and isolate (50:50) mixture was performed by varying the extrusion parameters, such as barrel temperature (138-180 °C), water feed (40-68%) and screw speed (400-1800 rpm). The effect of extrusion parameters on extruder responses [die pressure, product temperature, torque and specific mechanical energy (SME)] and product properties [colour, cutting force, cooking yield, microstructure and in vitro protein digestibility (IVPD)] was evaluated. The multiple regression analysis of the results revealed that the water feed had a significant negative linear effect on the extruder responses considered, as well as on colour difference and cutting force of extrudates. Screw speed had a positive linear effect on product temperature, SME and cooking yield. Barrel temperature affected extruder responses and product properties to a lesser extent. Scanning electron microscopy showed that denser microstructure and higher number of fibre layers were created by increasing temperature and screw speed along with decreasing water feed. The results of IVPD of selected extrudates showed that the increase in barrel temperature decreased the IVPD, whereas the increase in water feed resulted in higher IVPD. The screw speed had no significant effect on IVPD. The study demonstrates that the use of lupin protein is feasible to produce meat analogues with HME which could enhance the possibilities to meet the growing protein demands for human consumption. © 2018 Society of Chemical Industry.


Activation of GABAA receptors in the medial prefrontal cortex produces an anxiolytic-like response.
There has been increasing evidence that the γ-aminobutyric acid (GABA)ergic system is involved in the neurobiology of anxiety. The present study aimed to investigate the role of GABAergic systems in the modulation of anxiety in the medial prefrontal cortex (mPFC) of rats using the elevated plus maze test. Rats were anaesthetised with a mixture of ketamine and xylazine, and then special cannulae were inserted stereotaxically into the mPFC. After 5-7 days of recovery, the effects of intra-mPFC administration of GABAergic agents were studied. Bilateral injection of the GABAA receptor agonist muscimol (0.25, 0.5 and 1 μg/rat) produces an anxiolytic-like effect, shown by significant increases in the percentage of open-arm time (%OAT) and percentage of open-arm entries (%OAE). Intra-mPFC administration of the GABAA receptor antagonist bicuculline (0.25, 0.5 and 1 μg/rat) produces significant anxiogenic-like behaviour. However, intra-mPFC injection of the GABAB receptor agonist baclofen (0.05, 0.1 and 0.2 μg/rat) and the GABAB receptor antagonist CGP35348 (5, 10 and 15 μg/rat) did not alter %OAT and %OAE significantly. The results of the present study demonstrate that the GABAergic system of the mPFC modulates anxiety-related behaviours of rats through GABAA receptors.


Delivery room desaturations and bradycardia in the early postnatal period of healthy term neonates - a prospective observational study.
It has been suggested that desaturations and bradycardia precede acute life-threatening events (ALTE) and that ALTE is more common in the delivery room than later in life. However, frequency, duration and severity of desaturations in the first hours of life and additional risk factors have not readily been studied. Term neonates (n = 100) were monitored for the first two hours after birth by pulse oximetry. The impact of maternal and perinatal factors on the frequency and severity of desaturations (<85%) and bradycardia (<80/min) was evaluated. Desaturations were detected in 30%, prolonged desaturations in 25% of infants. Desaturations were observed significantly more often in infants born by planned Cesarean section (pCs) compared to other modes of delivery (pCs 20/49; others 10/51; p = .029). Desaturations were also more frequent in infants diagnosed with neonatal infection (NI) or infants born to a mother with gestational diabetes (GDM), although not significantly. No bradycardia <80/min was detected. In our collective 4% of healthy term neonates had prolonged, clinically relevant desaturations in the first hours after birth. The mode of delivery and maternal risk factors may increase the risk for these events. However, our cohort was too small to detect any ALTE or SIDS and determine potential risk factors for these events. Our data lay ground for a large-scale prospective trial to investigate whether the mode of delivery could be an indication for general pulse oximetry monitoring of newborn in the delivery room.


Determination of breast cancer response to bevacizumab therapy using contrast-enhanced ultrasound and artificial neural networks.
The purpose of this study was to evaluate contrast-enhanced ultrasound and neural network data classification for determining the breast cancer response to bevacizumab therapy in a murine model. An ultrasound scanner operating in the harmonic mode was used to measure ultrasound contrast agent (UCA) time-intensity curves in vivo. Twenty-five nude athymic mice with orthotopic breast cancers received a 30-microL tail vein bolus of a perflutren microsphere UCA, and baseline tumor imaging was performed using microbubble destruction-replenishment techniques. Subsequently, 15 animals received a 0.2-mg injection of bevacizumab, whereas 10 control animals received an equivalent dose of saline. Animals were reimaged on days 1, 2, 3, and 6 before euthanasia. Histologic assessment of excised tumor sections was performed. Time-intensity curve analysis for a given region of interest was conducted using customized software. Tumor perfusion metrics on days 1, 2, 3, and 6 were modeled using neural network data classification schemes (60% learning and 40% testing) to predict the breast cancer response to therapy. The breast cancer response to a single dose of bevacizumab in a murine model was immediate and transient. Permutations of input to the neural network data classification scheme revealed that tumor perfusion data within 3 days of bevacizumab dosing was sufficient to minimize the prediction error to 10%, whereas measurements of physical tumor size alone did not appear adequate to assess the therapeutic response. Contrast-enhanced ultrasound may be a useful tool for determining the response to bevacizumab therapy and monitoring the subsequent restoration of blood flow to breast cancer.


Cognitive clusters in first-episode psychosis: Overlap with healthy controls and relationship to concurrent and prospective symptoms and functioning.
To identify cognitive subgroups (comprising neurocognition and social cognition domains) within first-episode psychosis (FEP) patients including a healthy control group for comparison. Predictive validity of cognitive clusters in relation to symptoms and functioning was also investigated. A comprehensive cognitive battery was administered to 133 FEP participants and 46 healthy controls. Ward's method hierarchical agglomerative cluster analysis with k-means verification was used to determine clusters. Clusters were externally validated and 6-month predictive validity was also examined. Three distinct clusters were identified and were defined by degree of impairment rather than specific deficit profiles. Social-cognitive performance mirrored neurocognitive performance in each cluster. Cluster 1 was characterized by significant widespread cognitive impairments (1-2 SD below the mean) and solely comprised FEP participants (n = 24). Cluster 2 suggested moderately impaired cognitive functioning (within 0.5 SD below the mean), and comprised mostly FEP participants and 2 healthy controls (n = 73). Cluster 3 showed a pattern of cognitively intact performance across domains and comprised 37 FEP participants and 44 healthy controls (n = 81). Premorbid IQ, negative symptom severity, and functioning were significantly associated with cluster membership at baseline. At 6-month follow-up, cluster membership remained significantly associated with negative symptoms and functioning. The heterogeneity of cognition in FEP may be based on degree of impairment across both neurocognitive and social-cognitive domains. Cognitive clusters were associated with symptom and functional outcome, suggesting that measurement of cognition at entry to treatment may be useful for prognosis and treatment. (PsycINFO Database Record


The role of regional quality control programs in the practice of laboratory medicine in the United States.
Since their initiation in 1967, Regional Quality Control Programs have expanded, and they are now accessible to all clinical laboratories in the United States. Based on input from large numbers of laboratories analyzing the same lots of control material for chemistry, hematology, and coagulation, the programs provide computer-generated intralaboratory statistics for day-to-day precision and interlaboratory comparative statistics for relative precision and accuracy. Nearly half the clinical laboratories in the United States currently participate in Regional Quality Control Programs in chemistry. These voluntary programs are coordinated by voluntary professional groups or by the manufacturers of control materials. Professionally directed programs are, for the most part, supervised by committees of state pathology societies.


An infant and mother with severe B12 deficiency: vitamin B12 status assessment should be determined in pregnant women with anaemia.
The vitamin B12 status of infants depends on maternal B12 status during pregnancy, and during lactation if breastfed. We present a 9-month-old girl who was admitted to the metabolic unit for assessment of developmental delay. She was exclusively breastfed and the introduction of solids at 5 months was unsuccessful. Investigations revealed pancytopenia, undetectable B12 and highly elevated methylmalonic acid and homocysteine. Methylmalonic acid and homocysteine normalised following B12 injections. Marked catch-up of developmental milestones was noted after treatment with B12. Investigations of parents showed normal B12 in the father and combined B12 and iron deficiency in the mother. Maternal B12 deficiency, most likely masked by iron deficiency, led to severe B12 deficiency in the infant. Exclusive breastfeeding and a subsequent failure to wean exacerbated the infant's B12 deficiency leading to developmental delay. This case highlights the need for development of guidelines for better assessment of B12 status during pregnancy.


[X-ray photoelectron spectroscopy and mass spectrum study of tin and germanium compounds].
The relationship between the chemical displacement of binding energy and the different chemical environment for tin and germanium compounds was studied by means of X-ray photoelectron spectroscopy and mass spectrum.


Growth-dependent behavioral difference in bacterial chemotaxis.
Cells can adjust to their growth environments and regulate their behavior accordingly. To study how cells accomplish this growth-dependent adjustment from the molecular to the behavioral level, we used bacterial chemotaxis as a model system to explore the behavioral difference for bacteria grown in nutrient-rich and nutrient-poor media. We found that bacteria grown in a nutrient-poor medium exhibit faster chemotaxis adaptation, and this enables them to respond more rapidly to a changing environment and increases their ability to localize to a nutrient concentration peak. We identified the molecular mechanisms behind this behavioral difference through coarse-grained modeling, and demonstrated its physiological consequences by simulating bacterial chemotactic motion in spatiotemporally varying environments and in a static environment with a nutrient concentration peak.


Advances in contraception: vaginal contraceptive rings.
The vaginal contraceptive ring is very effective and user dependent. In this article, we will discuss the different types of vaginal contraceptive rings, namely, the etonogestrel/ethinyl estradiol (ENG/EE) ring (NuvaRing, Merck, Rahway, NJ, USA) and the segesterone acetate (SA)/EE (Annovera, Mayne Pharma, Raleigh, NC, USA) ring. The details of dosing and administration, indications, advantages, disadvantages, and cost-effectiveness are presented. This literature review was conducted using PubMed and Google Scholar. The search terms included 'vaginal contraceptive ring', 'etonogestrel/ethinyl estradiol ring', and 'segesterone acetate/ethinyl estradiol ring'. The search was then sorted by year from 2000 until present, and the most recent articles were reviewed. The purpose of this article is to provide a comprehensive reference on the two vaginal contraceptive rings widely used in the United States for clinicians to guide management. Both vaginal contraceptive rings are combination of hormonal contraceptives that suppress ovulation and create physiologic conditions unfavorable for pregnancy. The ENG/EE ring is designed to be replaced monthly, while the SA/EE ring is a single device used over the course of 1 year. Common side effects of both devices include headaches, nausea, vomiting, and vaginitis. Serious adverse reactions can occur with the vaginal contraceptive rings including venous thromboembolism, psychiatric events, and hypersensitivity. Both devices are contraindicated in patients at high risk for arterial or venous thrombotic events, patients with a history of breast cancer or other estrogen/progesterone cancers, and patients with severe liver disease. Overall, the vaginal contraceptive ring is well tolerated and liked by patients. Patients should be well counseled on known severe adverse reactions. The vaginal contraceptive ring is more expensive than other forms of contraception and this should be an important point of discussion with patients.


Diagnosis of cystic fibrosis by sweat testing: age-specific reference intervals.
To develop reference intervals (RIs) for sweat chloride and sodium in healthy children, adolescents, and adults. Healthy, unrelated subjects aged from 5 to >50 years and subjects who were pancreatic insufficient with cystic fibrosis (CF) were recruited. Sweat collection was performed on all subjects with the Wescor Macroduct system. Sweat electrolytes were analyzed with direct ion selective electrodes. DeltaF508 mutation analysis was performed on the healthy subjects >/=15 years old. A total of 282 healthy and 40 subjects with CF were included for analysis. There was no overlap of sweat chloride between the group with CF and the group without CF, but there was some overlap of sweat sodium. Sweat chloride increased with age, with the rate of increase slowing progressively to zero after the age of 19 years. The estimated median (95% RI) for sweat chloride were: 5 to 9 years, 13 mmol/L (1-39 mmol/L); 10 to 14 years, 18mmol/L (3-47 mmol/L); 15 to 19 years, 20 mmol/L (3-51mmol/L); and 20+ years 23 mmol/L (5-56mmol/L). We have successfully developed the age-related RI for sweat electrolytes, which will be useful for clinicians interpreting sweat test results from children, adolescents, and adults.


[The role of caspases in the apoptosis process].
Activation of caspases is the key event during apoptosis. Abnormalities of this phenomenon play an important role in the pathogenesis of several disorders and may have important clinical implications, including the development of novel therapeutic strategies. Currently, these problems are extensively investigated in several experimental and clinical studies.


Pneumo-Renal Syndrome in Anti- Neutrophil Cytoplasm Antibody (ANCA)-Associated Small-Vessel Vasculitis.
We aimed to evaluate the prevalence of lung hemorrhage, its determinants and its prognostic significance in adults patients with severe kidney involvement due to ANCA-associated vasculitis diagnosed and treated in a nephrology department. Seventy-five patients consecutively diagnosed by kidney biopsy with crescentic pauci-immune glomerulonephritis entered this cohort study and were grouped according to the presence of diffuse alveolar hemorrhage (DAH - diagnosed as diffuse alveolar pattern on chest radiographs and anemia without evidence of another external bleeding). ANCAs were assessed by capture PR3-ANCA and MPO-ANCA ELISA or by indirect immunofluorescence. Patients were followed for a median period of 38 (11.7; 65.8) months. The median age was 61.6 years. Median creatinine was 5.7 mg/dL and 17% of the patients needed temporary dialysis. Most of the patients (76%) had MPO-ANCA; 31% had pneumo-renal syndrome. DAH patients had more severe and active kidney disease, as reflected by higher serum creatinine (7.1 mg/dL vs 4.45 mg/dL; p=0.006) and higher hematuria (610/mm3 vs 230/mm3, p=0.003). The risk of DAH was not influenced by gender, age or ANCA specificity, but by smoking (smokers had a 4 (95%CI 1.18-14.2; p=0.002) times higher the risk of lung hemorrhage) and by season (patients diagnosed in winter and autumn had a 6 (95% CI 1.6-20.9; p=0.005) times higher the risk of lung hemorrhage). The proportion of responders and of patients with relapses, and time to maintenance dialysis or to death were similar irrespective to the occurrence of DAH at presentation. In patients with ANCA associated pauci-immune glomerulonephritis, cold season, smoking and active kidney disease, but not ANCA specificity or inflammation were associated with lung hemorrhage. Although diffuse alveolar hemorrhage was the main cause of death, it was not related to short- or long-term outcome.


Predictors of Maternal Mortality and Prognostic Models in Obstetric Patients.
The use of predictive models has been proposed as a potential tool to reduce maternal morbidity and mortality, by aiding in the timely identification of potential high-risk patients. Prognostic models in critical care have been used to characterize the severity of illness of specific diseases. Physiological changes in pregnancy may result in general critical illness prediction models overestimating mortality in obstetric patients. Models that specifically reflect the unique characteristics of obstetric patients may have better prognostic value. Recently developed tools have focused on identifying at-risk patients before they require intensive care unit (ICU) admission to target early interventions and prevent acute clinical decompensation. The aim of the newest scoring systems, specifically designed for groups of obstetric patients receiving non-ICU care, is to reduce maternal morbidity and mortality by identifying early high-risk patients and initiating prompt effective medical responses.


The Impact of Implant Fixation Type on Reoperation Rates Following Endoprosthetic Reconstruction Surgery.
Prospective evidence supporting the use of cemented or uncemented implants in endoprosthetic reconstruction is lacking. The present study aimed to determine the effect of cemented fixation compared with uncemented fixation on the rate of all-cause reoperation at 1 year postoperatively. This is a secondary analysis of the Prophylactic Antibiotic Regimens In Tumor Surgery (PARITY) trial. A total of 503 patients who underwent surgical excision and endoprosthetic reconstruction of a lower-extremity bone tumor were included in this analysis. A multivariate Cox proportional hazards model was utilized to assess the independent relationship between fixation group and implant survivorship, with all-cause reoperation as the end point. There were 388 cemented implants and 115 uncemented implants. Participants had a mean age of 42.7 years (standard deviation, 22.0 years), and 59% were male. Overall, 131 reoperations were identified over the 1-year follow-up period. There were no significant differences found in all-cause reoperation (hazard ratio [HR], 1.05; 95% confidence interval [CI], 0.70 to 1.57; p = 0.761), septic reoperation, or aseptic reoperation between cemented and uncemented fixation at 1 year postoperatively. The Cox regression analysis demonstrated that total operative time (HR per hour, 1.10; 95% CI, 1.02 to 1.20; p = 0.019) was an independent predictor of reoperation. The risk of reoperation was lower in patients with benign aggressive disease (HR, 0.11; 95% CI, 0.02 to 0.80; p = 0.029) or metastatic bone disease (HR, 0.30; 95% CI, 0.11 to 0.85; p = 0.023). Patients who underwent cemented fixation showed clinically meaningful functional improvement at 1 year postoperatively. Cemented compared with uncemented fixation has no effect on 1-year all-cause reoperation rates in endoprosthetic reconstruction surgery. Further research is required to investigate the long-term survival of cemented versus uncemented implants. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.


A Multiple Sensors Platform Method for Power Line Inspection Based on a Large Unmanned Helicopter.
Many theoretical and experimental studies have been carried out in order to improve the efficiency and reduce labor for power line inspection, but problems related to stability, efficiency, and comprehensiveness still exist. This paper presents a multiple sensors platform method for overhead power line inspection based on the use of a large unmanned helicopter. Compared with the existing methods, multiple sensors can realize synchronized inspection on all power line components and surrounding objects within one sortie. Flight safety of unmanned helicopter, scheduling of sensors and exact tracking on power line components are very important aspects when using the proposed multiple sensors platform, therefore this paper introduces in detail the planning method for the flight path of the unmanned helicopter and tasks of the sensors before inspecting power lines, and the method used for tracking power lines and insulators automatically during the inspection process. To validate the method, experiments on a transmission line at Qingyuan in Guangdong Province were carried out, the results show that the proposed method is effective for power line inspection.


Creating new knowledge for ruminant reproduction from rapidly expanding and evolving scientific databases.
Declining fertility is a major problem for the dairy industry. Recent developments of Omics-technologies facilitate a comprehensive analysis of molecular patters in gametes, embryos and tissues of the reproductive tract which may help to identify the reasons for impaired fertility. Large Omics-datasets require appropriate bioinformatics analysis in the context of rapidly expanding and evolving scientific databases. This overview summarizes the current status of ruminant genome projects, describes currently existing resources for ruminant genomics, transcriptomics and proteomics as well as databases and tools for the interpretation and exploitation of transcriptomics and proteomics datasets. Gene set enrichment analysis (GSEA) and transcription factor binding site (TFBS) analyses are strategies for the identification of regulatory genes. In general, the comprehensive analysis of molecular traits by Omics-technologies can enhance the interpretation of genome-wide association studies, providing insights into the biological pathways linking genotype and phenotype, and their modulation by endogenous and environmental factors.


Effect of fibroblasts on tracheal epithelial regeneration in vitro.
Several artificial grafts for covering deficient trachea have been produced through tissue engineering. Recently, our group clinically used an artificial trachea made from collagen sponge for patients with noncircumferential tracheal resection. However, the slowness of epithelial regeneration on the surface of the artificial trachea was confirmed as one particular problem. In this study, we co-cultured tracheal epithelial cells with fibroblasts and examined effects of fibroblasts on epithelial regeneration in vitro. Fibroblasts activated epithelial cell proliferation and migration. In co-culture with fibroblasts, epithelial cells reconstructed pseudostratified epithelium, which was composed of ciliated, goblet, and basal cells. Furthermore, a basement membrane was reconstructed between epithelial cells and fibroblasts, and integrin beta4 was also observed there. Fibroblasts rapidly increased mucin secretion by epithelial cells. These results indicate that stimulatory effects of fibroblasts on epithelial cell migration, proliferation, and differentiation would reduce the time required for covering of epithelial cells on the defect of luminal surface and hasten regeneration of morphologically and functionally normalized epithelium involving the reconstruction of basement membrane.


CCL11 promotes angiogenic activity by activating the PI3K/Akt pathway in HUVECs.
CCR3, the receptor for CCL11, is expressed on the surface of immune cells and even on non-immune cells. CCL11-CCR3 interactions can promote cell migration and proliferation. In this study, we investigated the effect of CCL11 on angiogenesis in HUVECs and also examined the molecular mechanisms of this process. We found that CCL11 induced mRNA transcription and protein expression of CCR3 in HUVECs. Moreover, the scratch wound healing assay and MTS proliferation assay both demonstrated that CCL11 promotes endothelial cell migration and induces weak proliferation. CCL11 directly induced microvessel sprouting from the rat aortic ring; these effects occurred earlier and to a greater extent than with VEGF stimulation. Furthermore, CCL11-induced phosphorylation of Akt was abolished by PI3K inhibitors. siRNA-mediated knockdown of CCR3 led to a significant reduction of PI3K phosphorylation. However, the phosphorylation levels of ERK1/2 were not changed, even after CCL11 treatment. Cumulatively, our data suggest that the CCL11-CCR3 interaction mainly activates PI3K/Akt signal transduction pathway in HUVECs.


TARGETED LEVOTHYROXINE THERAPY FOR TREATMENT OF CONGENITAL HYPOTHYROIDISM.
The purpose of this study was to determine if infants with congenital hypothyroidism (CH) whose initial dose of levothyroxine (LT4) is based on thyroid gland anatomy require fewer dose adjustments in the first 6 months of life than those who were started empirically on LT4. Newborns with CH who had a thyroid ultrasound performed at diagnosis were eligible for this prospective, historical case-controlled study. The daily LT4 dose prescribed was based on results on the thyroid ultrasound as follows: 15 mcg/kg for athyreosis, 12 mcg/kg for a dysgenetic thyroid, and 10 mcg/kg for an anatomically normal gland. Routine labs according to standard guidelines were obtained, and the number of dose adjustments over the first 6 months of therapy was recorded. Each study participant was matched with 2 historical controls with CH based on sex and thyroid anatomy. Twenty-two subjects (10 with athyreosis, 4 with dysgenetic glands, and 8 with anatomically normal glands) were matched to 44 controls. There was no significant difference in the overall number of adjustments in the study group compared to controls (P = .74). However, there were significantly fewer adjustments made for undertreatment (P = .03) and significantly more adjustments made for overtreatment (P = .006) in subjects with athyreosis compared to controls. Targeted LT4 therapy does not appear to decrease the overall frequency of dose adjustments for infants with CH. However, 15 mcg/kg/day appears to exceed thyroid hormone requirements in infants with CH due to athyreosis. CH = congenital hypothyroidism LT4 = levothyroxine OT = overtreatment T4 = thyroxine TSH = thyroid-stimulating hormone UT = undertreatment.


Evaluating borderline students.
While it was difficult for our faculty to face the disparity which arose in deciding whether or not to pass Anne, many important points were raised which strengthened the evaluation process particularly in the case of the borderline student. Newer faculty members related uneasiness in being specific and directive with "borderline" students. Experienced faculty offered suggestions on overcoming this fear and finding support among peers. Open discussion provided a forum for the exchange of ideas and philosophies. Though no definitive solutions were uncovered we judged this workshop to be a valuable learning experience with broad appeal across a very diverse faculty.


What makes pathogens pathogenic.
Metazoans contain multiple complex microbial ecosystems in which the balance between host and microbe can be tipped from commensalism to pathogenicity. This transition is likely to depend both on the prevailing environmental conditions and on specific gene-gene interactions placed within the context of the entire ecosystem.


Genetic mapping of genes for susceptibility to black spot disease in Japanese pears.
Black spot disease, which is caused by the Japanese pear pathotype of Alternaria alternata (Fr.) Keissler, is one of the most harmful diseases in Japanese pear cultivation. We identified the exact positions and linkage groups (LGs) of the genes for susceptibility to black spot in the Japanese pear (Pyrus pyrifolia Nakai) cultivars 'Osa Nijisseiki' (gene Ani) and 'Nansui' (gene Ana). Segregation of susceptibility and resistance fitted the expected ratio of 1:1 in progeny of 'Nansui' but showed a slight distortion in progeny of 'Osa Nijisseiki'. We mapped the genes for susceptibility to black spot in both populations using a genome scanning approach. The simple sequence repeat (SSR) markers CH04h02 and CH03d02 showed tight linkage to Ani and Ana. Although Ani and Ana are derived from different sources, both genes are located at the top region of LG 11. Information about the positions of the susceptibility genes and the molecular markers linked to them will be useful for marker-assisted selection in pear breeding programs.


Long Distance Modulation of Disorder-to-Order Transitions in Protein Allostery.
Elucidation of the molecular details of allosteric communication between distant sites in a protein is key to understanding and manipulating many biological regulatory processes. Although protein disorder is acknowledged to play an important thermodynamic role in allostery, the molecular mechanisms by which this disorder is harnessed for long distance communication are known for a limited number of systems. Transcription repression by the Escherichia coli biotin repressor, BirA, is allosterically activated by binding of the small molecule effector biotinoyl-5'-AMP. The effector acts by promoting BirA dimerization, which is a prerequisite for sequence-specific binding to the biotin biosynthetic operon operator sequence. A 30 Å distance separates the effector binding and dimerization surfaces in BirA, and previous studies indicate that allostery is mediated, in part, by disorder-to-order transitions on the two coupled sites. In this work, combined experimental and computational methods have been applied to investigate the molecular basis of allosteric communication in BirA. Double-mutant cycle analysis coupled with thermodynamic measurements indicates functional coupling between residues in disordered loops on the two distant surfaces. All atom molecular dynamics simulations reveal that this coupling occurs through long distance reciprocal modulation of the structure and dynamics of disorder-to-order transitions on the two surfaces.


Ambulatory surgery in a university setting.
Establishment of an ambulatory anesthesia and surgery program in a university teaching hospital presents difficulties. A successful program of this nature, the "Day Op program," was begun at the North Carolina Memorial Hospital in December 1972. Through December 1974, of all surgery performed in our operating rooms, 2,590 cases, (17%) were Day Op cases. Various types of anesthesia were used, and a high percentage of endotracheal intubations were performed. The hospital admission rate was 1.54%. Many difficulties were encountered, and much satisfaction was obtained, in the management of the program. The Day Op room has proved to be a major part of the success of the program.


[Compartmentalization and plasticity of the microtubule network].
Cytoplasm organization greatly depends on the cytoskeleton and especially on microtubules. Their multiple roles comprise for instance long-distance vesicular traffic or the organization of several signalling pathways. A variety of cellular functions require highly dynamic microtubules, which alternate between growing and shrinking phases. Meanwhile, other functions use stable microtubules, in which tubulin often bears multiple post-translational modifications like acetylation. Recent progress has been made in understanding some molecular mechanisms that control microtubule dynamics or tubulin acetylation. These mechanisms reveal the high plasticity of microtubules and point out the importance of their compartmentalization at structural and functional levels.


Solution structure of the IRF-2 DNA-binding domain: a novel subgroup of the winged helix-turn-helix family.
The transcription of interferon (IFN) and IFN-inducible genes is mainly regulated by the interferon regulatory factor (IRF) family of proteins, which recognize a unique AAGTGA hexamer repeat motif in the regulatory region of IFN genes. A DNA-binding domain of approximately 100 amino acids has been commonly found in the IRF family of proteins, but it has no sequence homology to known DNA-binding motifs. Elucidation of the structures of members of the IRF family is therefore useful to the understanding of the regulation and evolution of the immune system at the structural level. The solution structure of the DNA-binding domain of interferon regulatory factor-2 (IRF-2) has been determined by NMR spectroscopy. It is composed of a four-stranded antiparallel beta sheet and three alpha helices, and its global fold is similar to those of the winged helix-turn-helix (wHTH) family of proteins. A long loop (Pro37-Asp51) is found immediately before the HTH motif, which is not found in other wHTH proteins. The NMR signals of residues in this long loop, as well as the second helix of the HTH motif, are strongly affected upon the addition of the hexamer repeat DNA, suggesting that these structural elements participate in DNA recognition and binding. The structural similarity of the DNA-binding domain of IRF-2 with those of proteins in the wHTH family shows that the IRF proteins belong to the wHTH family, even though there is no apparent sequence homology among proteins of the two families. The sequential structure alignment program (SSAP) shows that IRF-2 has a slightly different structure from typical wHTH proteins, mainly in the orientation of helix 2. The IRF family of proteins should therefore be categorized into a subfamily of the wHTH family. The evidence here implies that the evolutional pathway of the IRF family is distinct from that of the other wHTH proteins, in other words, the immune system diverged from an evolutional stem at an early stage.


Improving Influenza and Pneumococcal Vaccination Rates in Ambulatory Specialty Practices.
Background. Influenza and pneumococcal vaccinations are recommended for elderly and high-risk patients; however, rates of adherence are low. We sought to implement influenza and pneumococcal vaccine initiatives in 4 different ambulatory specialty practices, using 3 unique approaches. Methods. Four specialties with high-risk patient populations were selected for intervention: allergy (asthma), infectious disease (ID) (human immunodeficiency virus), pulmonary (chronic lung disease), and rheumatology (immunocompromised). Allergy and ID focused on influenza vaccination, and pulmonary and rheumatology focused on pneumococcal vaccination. We used 3 strategies for quality improvement: physician reminders, patient letters, and a nurse-driven model. Physicians were provided their performance data on a monthly basis and presented trended data on a quarterly basis at staff meetings. Results. All 4 specialties developed processes for improving vaccination rates with all showing some increase. Higher rates were achieved with pneumococcal vaccine than influenza. Pneumococcal vaccine rates showed steady improvement from year to year while influenza vaccine rates remained relatively constant. Allergy's influenza rate was 59% in 2011 and 64% in the 2014 flu season. Infectious disease influenza rates moved from 74% in the 2011 flu season to 86% for the 2014 season. Pneumococcal vaccine in pulmonary patients' rate was 52% at the start of intervention in February 2009 and 79% as of January 2015. Rheumatology rates rose from 50% in February 2009 to 87% in January 2015. Conclusions. Integrated routine workflow and performance data sharing can effectively engage specialists and staff in vaccine adherence improvement. Influenza vaccination may require other approaches to achieve the rates seen with pneumococcal vaccine.


Refined localization and yeast artificial chromosome (YAC) contig--mapping of genes and DNA segments in the 7q21-q32 region.
The chromosome localizations for 159 gene and DNA segments have been refined to one of five intervals in the 7q21-132 region through hybridization analysis with a panel of somatic cell hybrid lines. Seventy-two of these chromosome 7 markers are also mapped on common or overlapping yeast artificial chromosome (YAC) clones. In addition, the breakpoints of chromosome rearrangement contained in five of the somatic cell hybrid lines have been defined by flanking probes within YAC contigs. To provide a framework for further mapping of the 7q21-q32 region, we have established the physical order of a set of reference markers: cen-(COL1A2-D7S15-CYP3A4-PON)-D7S456-(brea kpoint contained in cell hybrid 1EF2/3/K017)-GUSB-D7S186-ASL-(PGY1-PGY3 -GNB2-EPO-ACHE)-D7S238-(proximal breakpoint in GM1059-Rag5)-D7S240-(CUTL1-PLANH1)-(breakp oints in 1CF2/5/K016 and 2068Rag22-2)-(PRKAR2B-D7S13)-LAMB1-(breakpoint in JSR-17S)-DLD-D7S16-MET-WNT2-CFTR-D7S8-tel.


A convenient allylsilane-N-acyliminium route toward indolizidine and quinolizidine alkaloids.
This review relates all the results that we obtained in the field of the total synthesis of indolizidine and quinolizidine alkaloids using a strategy of the addition of an allylsilane on an N-acyliminium ion. In this paper, we describe the synthesis of racemic indolizidine 167B and chiral indolizidines: (-)-indolizidines 167B, 195B, 223AB, (+)-monomorine, (-)-(3R,5S,8aS)-3-butyl-5-propylindolizidine and (-)-dendroprimine. Next, we relate the synthesis that we have developed in the quinolizidines field: (+/-)-myrtine and epimyrtine, (+/-)-lasubines I and II and chiral quinolizidines: (+)-myrtine, (-)-epimyrtine, (-)-lasubines I and II and (+)-subcosine II.


Combined Targeting of mTOR and Akt Using Rapamycin and MK-2206 in The Treatment of Tuberous Sclerosis Complex.
Tuberous sclerosis complex (TSC), caused by loss-of-function mutations in the TSC1 or TSC2 genes, is an autosomal dominant disease characterized by benign tumor formation in multiple organs. Hyperactivation of mammalian target of rapamycin (mTOR) is the primary alteration underlying TSC tumor. Thus, rapamycin, as an mTOR specific inhibitor, has been assumed as a potential drug for the treatment of TSC. However, its application in TSC patients has been limited due to side effects. By analyzing Tsc1- or Tsc2-null mouse embryonic fibroblasts (MEFs), we found that loss of TSC1 or TSC2 led to a decreased sensitivity to MK-2206, a novel allosteric Akt inhibitor. Ectopic expression of a constitutively activated Akt (myristoylated Akt-1, myrAkt-1) sensitized Tsc2-null and Tsc1-null MEFs to MK-2206. Furthermore, MK-2206 increased the cytotoxicity of rapamycin in Tsc1-/- or Tsc2-/- MEFs. Moreover, the benefit of the combinatorial treatment was also demonstrated in a TSC xenograft mouse model. We conclude that the combination of rapamycin and MK-2206 may be utilized as a new therapeutic regimen for TSC.


Risk Factors of Lower Urinary Tract Syndrome among Ketamine Users.
This study investigated the risk factors of ketamine associated-lower urinary tract symptoms (LUTS), such as duration of use, dosage of ketamine, co-occurring substance use of other psychoactive drugs, comorbidities, and depression. This study was a cross-sectional survey. LUTS was assessed with the O'Leary symptom and problem index (OSPI) scores. We included the comorbidities of interstitial cystitis/painful bladder syndrome (IC/PBS) as comorbid factors. Depression was evaluated based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM 5). Duration of use, dosage of ketamine and the OSPI scores were subjected to log transformation because of the skewed distribution. Among 143 participating ketamine users, 25 (17.5%) had LUTS. Duration of ketamine use was significantly positively correlated with OSPI scores (adjusted β [95% CI], 0.21 [0.06-0.35] in log-log model), which equaled a 10% increase in months of ketamine-use increased OSPI scores by 2.02 %. Female and depression were significantly associated OSPI scores (adjusted β [95% CI], 0.20 [0.03-0.37], 0.49 [0.29-0.70], respectively in the log-linear model), with OSPI scores being 1.22 times higher in female, and 1.63 times higher in ketamine users with depression. Dosage of use was not significantly associated with OSPI scores (adjusted β [95% CI], 0.04 [-0.12 to 0.20], P = 0.64 in log-log model), likewise with comorbid diseases (adjusted β [95% CI], 0.07 [-0.08 to 0.21], P = 0.36 in log-linear model). Depression and longer duration of exposure to ketamine are significantly associated with the development of LUTS among ketamine users. Early evaluation and intervention of depression should be considered in patients of ketamine-associated LUTS.


Casualties of summer.
With the summer holiday period approaching, A&E departments in popular resorts are putting plans in place to deal with increased demand.


Chlamydia: its influence in chronic secretory otitis media.
Since Chlamydia trachomatis was isolated from middle ear effusions of neonates with natally acquired chlamydial infection (Tipple et al., 1979), there have been several studies to detect chlamydia in older children with chronic secretory otitis media, mainly by tissue culture. In this study, the aspirates of 106 middle ear effusions of 60 children with chronic secretory otitis media were investigated for the presence of C. trachomatis, other bacteria and viruses. An amplified enzyme-linked immunoassay was used to detect the presence of chlamydia. The bacteriological and virological results mirrored previous studies in the United Kingdom and no chlamydia were found. Chlamydia do not appear to be related to the aetiology of this disease in the population examined.


Prenatally elevated physiological arousal interferes with perceptual learning in bobwhite quail (Colinus virginianus) embryos.
Neonatal studies suggest elevated arousal can negatively influence perceptual and cognitive processes during early development. The authors explored this issue during the prenatal period by pharmacologically elevating physiological arousal in bobwhite quail (Colinus virginianus) embryos during exposure to a maternal call, then assessing preference for the familiar call following hatching. Embryos receiving norepinephrine showed a prenatal elevation in heart rate and failed to demonstrate a preference for the familiar call following hatching. Embryos not receiving norepinephrine showed no elevation in heart rate and demonstrated a preference for the familiar call. These results indicate elevated arousal can interfere with perceptual learning during the prenatal period and provide additional evidence for an optimal window of arousal necessary to foster species-typical perceptual functioning during early development.


Intracerebral infusion of the bispecific targeted toxin DTATEGF in a mouse xenograft model of a human metastatic non-small cell lung cancer.
The aim of this study is to investigate the anti-cancer effect of the bispecific diphtheria toxin (DT) based immunotoxin DTATEGF, which targets both the epidermal growth factor (EGF) receptor (EGFR) and the urokinase-type plasminogen activator (uPA) receptor (uPAR) in vitro and in vivo when delivered by convection-enhanced delivery (CED) via an osmotic minipump in a human metastatic non-small cell lung cancer (NSCLC) brain tumor mouse xenograft model. The effects of the bispecific immunotoxin DTATEGF, and monospecific DTAT, DTEGF and control DT at various concentrations were tested for their ability to inhibit the proliferation of human metastatic NSCLC PC9-BrM3 cells in vitro by MTT assay. A xenograft model of human metastatic NSCLC intracranial model was established in nude mice using the human NSCLC PC9-BrM3 cell line genetically marked with a firefly luciferase reporter gene. One microgram of DTATEGF in the treatment group or control DT in the control group was delivered intracranially by CED via an osmotic minipump. The bioluminescent imaging (BLI) was performed at day 7, 14, 1 month, 2 months, and 3 months. Kaplan-Meier survival curves for the two groups were generated. The brain tissue samples were stained by hematoxylin and eosin for histopathological assessment. In vitro, DTATEGF could selectively kill PC9-BrM3 cells and showed an IC(50) less than 0.001 nM, representing a more than 100- to 1000-fold increase in activity as compared to monospecific DTAT and DTEGF. In vivo, mice with tumors were treated intracranially with drug via CED where the results showed the treatment was successful in providing a survival benefit with the median survival of mice treated with DTATEGF being significantly prolonged relative to controls (87 vs. 63 days, P = 0.006). The results of these experiments indicate that DTATEGF kills the NSCLC PC9-BrM3 cell line in vitro, and when it is delivered via CED intracranially, it is highly efficacious against metastatic NSCLC brain tumors. DTATEGF is a safe and effective drug where further preclinical and clinical development is warranted for the management of metastatic brain tumors.


Mathematical modelling with Bayesian inference to quantitatively characterize therapeutic cell behaviour in nerve tissue engineering.
Cellular engineered neural tissues have significant potential to improve peripheral nerve repair strategies. Traditional approaches depend on quantifying tissue behaviours using experiments in isolation, presenting a challenge for an overarching framework for tissue design. By comparison, mathematical cell-solute models benchmarked against experimental data enable computational experiments to be performed to test the role of biological/biophysical mechanisms, as well as to explore the impact of different design scenarios and thus accelerate the development of new treatment strategies. Such models generally consist of a set of continuous, coupled, partial differential equations relying on a number of parameters and functional forms. They necessitate dedicated in vitro experiments to be informed, which are seldom available and often involve small datasets with limited spatio-temporal resolution, generating uncertainties. We address this issue and propose a pipeline based on Bayesian inference enabling the derivation of experimentally informed cell-solute models describing therapeutic cell behaviour in nerve tissue engineering. We apply our pipeline to three relevant cell types and obtain models that can readily be used to simulate nerve repair scenarios and quantitatively compare therapeutic cells. Beyond parameter estimation, the proposed pipeline enables model selection as well as experiment utility quantification, aimed at improving both model formulation and experimental design.


Youth Participatory Action Research for Health Equity: Increasing Youth Empowerment and Decreasing Physical Activity Access Inequities in Under-resourced Programs and Schools.
To address gaps in the youth participation and adolescent physical activity (PA) promotion literature, we examined the feasibility of youth participatory action research (YPAR) in (a) general aftercare (YPAR only) and (b) with a physical activity intervention, (YPAR + PA) to reach marginalized youth and impact individual empowerment and second-order change for equitable PA access. We intervened during middle school, a developmental stage conducive to changing health habits. We used a concurrent, mixed-method triangulation design. Participants were students (94% non-Hispanic Black/African American, 75% free/reduced lunch) in the southeastern United States. YPAR was adapted from online modules. Youth conducted photovoice, capturing and analyzing social/environmental factors contributing to inequities in their schools/programs. PA inequities emerged for girls. Findings indicated feasibility of YPAR with systems supports. Changes occurred at the individual and systems level in the YPAR + PA program. Sociopolitical skills, participatory behavior, and perceived control empowerment subdomains increased pre-post, and youth qualitative responses aligned. A follow-up interview with the director revealed all youth-proposed changes occurred. A feedback loop was developed for continued youth input. Youth-led changes to increase PA access have potential to decrease health disparities by generating unique solutions likely missed when adults intervene alone.


[Evaluation of thyroid cancer morbidity in Warsaw in 1987-1997].
The crude and standardized thyroid cancer incidence rates calculated for the period 1987-1997 in Poland increased from 0.5 to 0.9 and 0.5 to 0.8 per 100,000 men, and from 1.8 to 3.6 and 1.4 to 2.8 per 100,000 women. The incidence of the cancer in women in Warsaw doubled during the same period. The upward trend only slightly showed up in the male population of Warsaw. Mortality rates caused by the thyroid cancer in both sexes in Warsaw population declined over the years 1963-1997. The 5-year relative survival rates, calculated for the period 1985-1989, were lower in men than in women (respectively 66 and 49%). This fact can be partly explained by more frequent occurrence of anaplastic tumours in men than in women (respectively 14.2 and 7.8%).


[Uvetitis and multiple sclerosis].
To evaluate the type of uveitis, the time of the duration between the first ocular signs and establishing of the diagnosis of multiple sclerosis (MS), effect of the treatment, and the final visual acuity (VA). In a retrospective study, medical records of 41 patients (82 eyes) from the total of 1267 patients with uveitis treated at the Center for uveitis diagnosis and treatment at the Department of Ophthalmology of the Faculty Hospital and 1st Medical faculty, Charles University in Prague, Czech republic, during the period 1986-2003 were evaluated. The cohort consisted of 32 females and 9 males, mean age of 27 years (8-46 years). The mean follow-up period was 8 years (1-17 years). The cohort consisted of 41 patients (82 eyes), 32 females and 9 males. The mean age at the beginning of the uveitis was 27 years, at the time of the diagnosis of the MS 29.5 years. In 19 patients the starting of the uveitis preceded the manifestation of the systemic disease. In 23 patients, the uveitis was the first manifestation of MS. The most common type of uveitis in patients with MS was the intermediate uveitis (IMU) and vasculitis of retinal vessels. In 82% of patients, we were able during the follow-up period to stabilize the VA, or even to improve it. The systemic immunosuppressive treatment was necessary in 83 % of patients. The MS was the second most common systemic disease in uveitis patients. It is necessary to follow-up young patients with unclear etiology of IMU or vasculitis, because the systemic disease may develop even few years after the first sings of uveitis. The collaboration between the neurologist and the ophthalmologist is of a great importance.


Rapid characterization of metabolites in soybean using ultra high performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-Q-TOF-MS/MS) and screening for α-glucosidase inhibitory and antioxidant properties through different solvent systems.
This work was the first to investigate on the simultaneous characterization of metabolite profiles in soybean using UPLC-ESI-Q-TOF-MS/MS. Twenty two compositions were observed within 14 min from the methanol extract and confirmed as twelve isoflavones of three types and ten soyasaponins (Ab, Af, I-III, αg, βg, βa, γg, and γa). Moreover, the patterns of two chemicals showed considerable differences in seven solvent systems by HPLC analysis and their optimal extraction was achieved by 70% methanol (isoflavone: 4102.69 μg/g; soyasaponin: ten peaks). The second abundant isoflavones were detected in 50% methanol (4054.39 μg/g), followed by 30% methanol, 100% methanol, 10% methanol, CH2Cl2, and acetone extracts with 3134.03, 2979.49, 1681.33, 366.19, and 119.00 μg/g, respectively. Soyasaponins exhibited similar tendencies as those of isoflavones. The highest total phenolic was found as 2.10 ± 0.05 mg GAE/g in 70% methanol with remarkable differences by comparing other extracts. Specifically, this extract showed potent α-glucosidase inhibitory (81%) and antioxidant capacities (DPPH: 93% and ABTS: 95%) at a concentration of 1.0 mg/mL. Our results may be contributed to enhancing the value to functional foods and evaluating the secondary metabolites concern to antioxidant properties using solvent system in soybean.


Surgical Management of Unusual Biangular Mandibular Fractures.
Bilateral mandibular angle fractures, while representing a rarity among mandibular fractures, are a huge challenge of complex management for the maxillofacial surgeon. There are still many open questions regarding the ideal management of such fractures, including the following: the removal of the third molar in the fracture line, the best surgical approach, and the fixation methods. In this report the authors present the case of 40-year-old man presenting with a bilateral mandibular angle fracture referred to the Maxillofacial Surgery Department of Turin. Open reduction and internal fixation has been made for both sides. The left side third molar was removed and the internal fixation was achieved through internal fixation with one miniplate according to Champy's technique and transbuccal access for a 4-hole miniplate at the inferior border of the mandible. Right side third molar was not removed and fixation was achieved through intraoral access and positioning of a 4-hole miniplate along the external ridge according to Champy. An optimal reduction was achieved and a correct occlusion has been restored.


Ciglitazone, a novel inhibitor of lung apoptosis following hemorrhagic shock.
Apoptosis or programmed cell death has been demonstrated to play a role in the development of lung injury following hemorrhagic shock. A major pathway modulating the apoptotic response is the phosphatidylinositol 3-kinase/serine/threonine kinase (PI3K/Akt) pathway. Ciglitazone, a peroxisome proliferator-activated receptor-y (PPARy) ligand has previously been shown to attenuate lung inflammation following hemorrhagic shock. In vivo similar ligands have demonstrated anti-apoptotic effects with a reduction in organ injury in models of acute illness. In this study we examined the effect of ciglitazone on apoptosis and PI3K/Akt signaling in the lung following severe hemorrhage and resuscitation. Hemorrhagic shock was induced in male Wistar rats by withdrawing blood from the femoral artery to a mean arterial pressure of 50 mmHg. Animals were kept in shock for 3h at which time they were rapidly resuscitated by returning their shed blood. At the time of resuscitation and every hour thereafter, groups of animals received ciglitazone (10mg/kg) or DMSO intraperitoneally. Vehicle-treated rats had increased lung apoptosis following hemorrhage and resuscitation by Tunel staining. This was associated with increased activity of caspase-3. Ciglitazone treatment reduced lung apoptosis with a significant reduction in caspase-3 activity. This was associated with increased phosphorylation of the pro-survival kinase Akt. Thus, our data suggest that ciglitazone, a PPARy ligand, promotes cell survival in the lung following hemorrhagic shock.


New way of working: Professionals' expectations and experiences of the Culture and Health Project for clients with psychiatric disabilities: A focus group study.
There is a need for various types of interventions when meeting needs of clients with psychiatric disabilities and complementary interventions may also influence their well-being. The Culture and Health project, based on complementary interventions with 270 clients, was created in a county in Sweden for clients with psychiatric disabilities and for professionals to carry out the interventions. The aim of this study was to investigate the professionals' expectations regarding the project and their clients' possibilities for participating, and to investigate the professionals' experiences of the project after its completion. Focus group data with a total of 30 professionals participating were collected. A qualitative content analysis revealed four categories of the professionals' expectations before entering the project: "Clients' own possibilities and limitations for their development and independence", "Professionals' possibilities for supporting the clients", "Societal prerequisites", and "Expectations of a new way of working". Furthermore, the analysis regarding professionals' experiences after working with the project revealed three categories: "Adopting the challenges", "Having ways of working that function - prerequisites and possibilities", and "Meeting the future - an ambition to continue". Working in the Culture and Health project together with the clients in group-based activities was perceived as beneficial, although challenges arose. When implementing cultural activities, support from stakeholder organisations is needed.


Contribution by synaptic zinc to the gender-disparate plaque formation in human Swedish mutant APP transgenic mice.
Endogenous metals may contribute to the accumulation of amyloid plaques in Alzheimer's disease. To specifically examine the role of synaptic zinc in the plaque accumulation, Tg2576 (also called APP2576) transgenic mice (hAPP(+)) expressing cerebral amyloid plaque pathology were crossed with mice lacking zinc transporter 3 (ZnT3(-/-)), which is required for zinc transport into synaptic vesicles. With aging, female hAPP(+):ZnT3(+/+) mice manifested higher levels of synaptic zinc, insoluble amyloid beta, and plaques than males; these sex differences disappeared in hAPP(+):ZnT3(-/-) mice. Both sexes of hAPP(+):ZnT3(-/-) mice had markedly reduced plaque load and less insoluble amyloid beta compared with hAPP(+):ZnT3(+/+) mice. Hence, of endogenous metals, synaptic zinc contributes predominantly to amyloid deposition in hAPP(+) mice.


The heparan sulfate binding sequence of interferon-gamma increased the on rate of the interferon-gamma-interferon-gamma receptor complex formation.
Interferon-gamma (IFNgamma), in common with a number of growth factors, binds both to heparan sulfate or heparin-related molecules and to a specific high affinity receptor (IFNgammaR). Using surface plasmon resonance technology, kinetic analysis of the IFNgamma. IFNgammaR complex formation was performed with the extracellular part of IFNgammaR immobilized on a sensor chip. At the sensor chip surface, IFNgamma was bound by two IFNgammaR molecules with an affinity in the nanomolar range (0.68 nM). This binding was characterized by an important on rate, kon = 7.3 x 10(6) M-1.s-1, and an off rate, koff = 5 x 10(-3).s-1. This binding assay was used to investigate a possible role of heparin in the IFNgamma.IFNgammaR complex formation. In contrast to growth factors for which binding to heparin is usually required for high affinity receptor interaction, we found in this study that IFNgamma bound to heparin displayed a strongly reduced affinity for its receptor. This is consistent with the fact that a cluster of basic amino acids (KTGKRKR, called the C1 domain) in the carboxyl-terminal sequence of the cytokine was involved both in heparin and receptor recognition. To understand how a single domain of IFNgamma could be implicated in two discrete functions (i.e. binding to heparin and to IFNgammaR), we also analyzed in a detailed manner the role of the IFNgamma carboxyl-terminal sequence in receptor binding. Using forms of IFNgamma, with carboxyl terminus truncations of defined regions of the heparin binding sequence, we found that the C1 domain functioned by increasing the on rate of the IFNgamma.IFNgammaR binding reaction but was not otherwise required for the stability of the complex. Interactions between the IFNgamma carboxyl-terminal domain and IFNgammaR could increased the association rate of the reaction either by increasing the number of encounters between the two molecules or by favoring productive collisions. The mechanisms by which heparan sulfate regulates IFNgamma activity may thus include both control of selective protease cleavage events, which directly affect the cytokine activity, and also an ability to modulate the interaction of IFNgamma with the IFNgammaR via competitive binding to the C1 domain.


Association of hyaluronidase and breast adenocarcinoma invasiveness.
Hyaluronic acid (HA) is a component of the extracellular matrix (ECM) that exists as a high molecular weight polymer composed of alternating disaccharides, D-glucuronic acid and N-acetyl D-glucosamine. The interaction of hyaluronidase with HA results in the disruption of basement membrane integrity and produces an angiogenic response that has been implicated in tumor invasiveness and metastasis. Although hyaluronidase is present in several neoplasms, levels of hyaluronidase expression in breast cancer are not known. This investigation defines the correlation of elevated levels of hyaluronidase with breast adenocarcinoma invasiveness. Utilizing RT-PCR, RNA was extracted from paraffin embedded tissues (n=6) of patients diagnosed with fibrocystic breast changes, ductal carcinoma in situ (DCIS), and invasive adenocarcinoma. After constructing cDNA primers for base pairs 504 and 759 of the PH-20 gene (which is homologous to the hyaluronidase gene), PCR was performed and the products were visualized with ethidium bromide using gel electrophoresis. Invasive breast adenocarcinoma had a significantly higher level of hyaluronidase expression compared to other breast tissue samples; (32+/-15 vs. 8+/-3; p<0.03). Elevated levels of hyaluronidase correlated with invasive breast adenocarcinoma. Our data suggests that elevated levels of hyaluronidase are associated with breast adenocarcinoma invasive potential. Hyaluronidase may play an integral role in breast cancer invasion and metastasis.


Is the quality of occlusal contacts comparable after aligner and fixed orthodontic therapy? A non-randomized cohort comparison using computerized occlusal analysis during 6 months of retention.
Less than ideal contacts have been reported following aligner therapy, but it is considered a transitory problem, spontaneously resolving with the phenomenon of settling. Methods: Thirty-nine orthodontic patients (14 treated with aligners; 25 with fixed appliances) were evaluated with a digital occlusal analysis system (T-scan™10), assessing Maximum Intercuspation contact simultaneity, symmetry, and relative force distribution at treatment completion and after 3 and 6 months. No significant differences in occlusal contact quality were found between groups at treatment completion or follow-up. The center of force moved posteriorly and remained stable after 3 months but was located more anteriorly in females (p = 0.01). One-third of patients (both groups combined) had marked contact force asymmetry even after 6 months' retention. Conclusion: Occlusal contacts were comparable at completion of treatment with aligners or brackets and after 3-6 months of retention. Settling did not improve marked asymmetry in all patients.


Effectiveness and Cost-Utility Analysis of Different Doses of Irinotecan Plus Bevacizumab in Patients With Metastatic Colorectal Cancer: A Long-Term and Prospective Cohort Study.
Patients with metastatic colorectal cancer (mCRC) had oncological benefits with irinotecan dose escalation of FOLFIRI regimen combined with bevacizumab according to UGT1A1 genotypes in our previous study. In the current study, we performed a quality of life (QOL) outcome evaluation and cost-utility analysis of different irinotecan dose regimens in patients with mCRC. With inverse probability-of-treatment weighting (IPTW) matching on all covariates, 75 patients with dose escalation of irinotecan (study group) and 121 patients with the recommended dose of irinotecan (control group) were recruited between October 2015 and December 2019. The QOL outcome measures were Functional Assessment of Cancer Therapy-Colorectal, Beck Anxiety Inventory, Beck Depression Inventory, and SF-36; cost-utility outcome measures were medical direct costs, quality-adjusted life-years (QALYs), and incremental cost-utility ratios (ICURs). All mCRC patients exhibited a significant decrease in both emotional wellbeing and depression from pretherapeutic period to posttherapeutic 6th month (P < 0.05); however, from the posttherapeutic 1st year to the 2nd year, improvement in most QOL measures was significantly better in the study group than in the control group (P < 0.05). Over a 2-year time period, the study group had higher total medical direct costs than the control group (US$ 54,742 ± 14,013 vs. US$ 54,608 ± 9,673) and higher average QALYs gained (1.88 vs. 1.65), with an ICUR of US$ 583 per QALY gained. For patients with mCRC, irinotecan dose escalation appeared cost-effective with considerable QOL improvements during the study period. Further randomized, multi-institutional controlled trials are warranted to corroborate these results.


Individual fluorouracil dose adjustment in FOLFOX based on pharmacokinetic follow-up compared with conventional body-area-surface dosing: a phase II, proof-of-concept study.
To compare the efficacy and safety of pharmacokinetically (PK) guided fluorouracil (5-FU) dose adjustment vs. standard body-surface-area (BSA) dosing in a FOLFOX (folinic acid, fluorouracil, oxaliplatin) regimen in metastatic colorectal cancer (mCRC). A total of 118 patients with mCRC were administered individually determined PK-adjusted 5-FU in first-line FOLFOX chemotherapy. The comparison arm consisted of 39 patients, and these patients were also treated with FOLFOX with 5-FU by BSA. For the PK-adjusted arm 5-FU was monitored during infusion, and the dose for the next cycle was based on a dose-adjustment chart to achieve a therapeutic area under curve range (5-FU(ODPM Protocol)). The objective response rate was 69.7% in the PK-adjusted arm, and median overall survival and median progression-free survival were 28 and 16 months, respectively. In the traditional patients who received BSA dosage, objective response rate was 46%, and overall survival and progression-free survival were 22 and 10 months, respectively. Grade 3/4 toxicity was 1.7% for diarrhea, 0.8% for mucositis, and 18% for neutropenia in the dose-monitored group; they were 12%, 15%, and 25%, respectively, in the BSA group. Efficacy and tolerability of PK-adjusted FOLFOX dosing was much higher than traditional BSA dosing in agreement with previous reports for 5-FU monotherapy PK-adjusted dosing. Analysis of these results suggests that PK-guided 5-FU therapy offers added value to combination therapy for mCRC.


Get ready to GO! A biologist's guide to the Gene Ontology.
The Gene Ontology (GO) project provides a controlled vocabulary to facilitate high-quality functional gene annotation for all species. Genes in biological databases are linked to GO terms, allowing biologists to ask questions about gene function in a manner independent of species. This tutorial provides an introduction for biologists to the GO resources and covers three of the most common methods of querying GO: by individual gene, by gene function and by using a list of genes. [For the sake of brevity, the term 'gene' is used throughout this paper to refer to genes and their products (proteins and RNAs). GO annotations are always based on the characteristics of gene products, even though it may be the gene that is cited in the annotation.].


Horizontal Transmission of Beauveria bassiana (Hypocreales: Cordycipitaceae) and Metarhizium anisopliae (Hypocreales: Clavicipitaceae) in Musca domestica (Diptera: Muscidae).
Beauveria bassiana Vuillemin and Metarhizium anisopliae (Metschnikoff) Sorokin are fungi with potential for controlling Musca domestica L. However, the impact on this dipteral may vary depending on the fungal isolates and the methodology used. This study evaluated the pathogenicity of direct application and horizontal transmission of B. bassiana (CG240) and M. anisopliae (CG34) on adult M. domestica individuals. The impact of B. bassiana and M. anisopliae on M. domestica was evaluated at the concentrations 2 × 10(4), 2 × 10(5), 2 × 10(6), and 2 × 10(7) conidia/ml. Horizontal transmission was also estimated between sexes at different infection periods of the vector insect. The mortality of adult M. domestica individuals directly infected with B. bassiana was above 90%, and the mortality of those infected with M. anisopliae ranged from 25.50 to 97.78%. Horizontal transmission of B. bassiana caused the death of 100% of individuals, in turn, that of M. anisopliae killed 55% of male and 100% of female individuals. Horizontal transmission of fungi was negatively influenced by time. This study shows the potential of these fungi for controlling M. domestica, both with the direct implementation strategy and horizontal transmission. However, field studies are needed to evaluate the capacity to decrease the M. domestica population using these alternatives.


GnRH localization in the equine brain and infundibulum: an immunohistochemical study.
Immunohistochemical localization of the decapeptide gonadotropin releasing hormone (GnRH) in neural structures in the pony brain and infundibulum (INF) was conducted at the light-microscopic level. This procedure utilized an antiserum generated against GnRH conjugated to bovine serum albumin. In the rostral INF, GnRH was distributed mainly in the external layer, with greatest concentrations adjacent to the long capillary loops of the hypophyseal portal system. The intermediate portion of the INF contained the hormone throughout the external layer, especially in the dorsolateral regions just ventral and medial to the tuberoinfundibular sulcus (TIS) with lesser amounts dorsal to the TIS. Caudally, GnRH was very concentrated along the medial border of the Tis, and in small amounts within the medial portion of the INF just rostral to the mammillary bodies. Throughout the INF, reaction product was noted in the internal layer, although the concentration was less than that observed in the external layer. The hormone was localized in axons of the brain from the medial and lateral septal nuclei through the mammillary region. GnRH positive perikarya were localized in the lamina terminalis, infundibular nucleus and the caudal periventricular nucleus. Preabsorption of the specific antiserum with synthetic GnRH abolished staining in both axons and perikarya, whereas preabsorption with other hypothalamic peptides did not affect staining intensity.