Notch and NFkappaB signaling pathways: Do they collaborate in normal vertebrate brain development and function?
Both Notch and NFkappaB signaling pathways are well-known for regulating proliferation, differentiation and apoptosis. Recent studies have presented several lines of evidence supporting an integration of the Notch and NFkappaB signaling pathways in differentiation/maturation of a diverse range of cell types. It is notable that Notch and NFkappaB signaling pathways share many common features: (i) both are activated by common stimuli such as TNF-alpha and hypoxia, (ii) activated Notch (NICD) and NFkappaB mediate transcription by regulating corepressors such as SMRT/N-COR, and (iii) both regulate similar target genes such as Hes-1 and IkappaBalpha. This review expands on how the collaboration between these pathways may play an important role in the CNS. We will speculate on the mechanisms by which Notch and NFkappaB signaling may collaborate to regulate stem cell renewal and differentiation during brain development and function.


Current concepts of the treatment of adult brachial plexus injuries.
As the number of survivors of motor vehicle accidents and extreme sporting accidents increases, the number of people having to live with brachial plexus injuries increases. Although the injured limb will never return to normal, an improved understanding of the pathophysiology of nerve injury and repair, as well as advances in microsurgical techniques, have enabled the upper extremity reconstructive surgeon an opportunity to improve function in these life-altering injuries. The purpose of this review is to detail some of the current concepts of the treatment of adult brachial plexus injuries and give the reader an understanding of the nuances of the timing, available treatment options, and outcomes of treatment.


A Novel Phage Cocktail Therapy of the Urinary Tract Infection in a Mouse Model.
Escherichia coli (E. coli) is a major bacterial pathogen associated with many cases of serious infections, such as urinary tract infections (UTI) and meningitis intestinal. The rapid emergence of antimicrobial multidrug-resistant bacteria occurring worldwide has been attributed to the overuse of antibiotics. Alternative strategies must be developed to overcome antibiotic resistance. A promising alternative for the treatment of infections is the use of phages as antibacterial agents. A total of 90 female albino mice were randomly divided into three groups (n=30) and used for the induction of UTI. The animals were acclimatized in their cages for 24 h before inoculation and allowed to access chow and water freely. For UTI induction, the peri-urethral area was sterilized with 70% ethanol, and bacterial inoculation was then injected into the bladder through the urethra using a 24-gauge sterile Teflon catheter with an outer diameter of 0.7 mm and length of 19 mm. A single phage and a phage cocktail preparation have been evaluated for their therapeutic activity in the mouse model of chronic UTI induced by transurethral injection of two isolates of the uropathogenic E. coli 8 and E. coli 302. The results of the transurethral and intra-peritoneal injection of phage(s) that prepared on day 10 after the establishment of the mouse chronic model showed no effect of a single phage PEC80 in the treatment of UTI, whereas both administration routes of the phage cocktail preparation resulted in the clearance of bacteria from mice urine and homogenates of the urinary bladders and kidneys of the sacrificed mice after 24 h following the administration of phage cocktail dose. The high activity of the phage cocktail in the treatment of mouse chronic model of UTI is attributed to the broader host range of the phage cocktail, compared to the very narrow host range of the phage PEC80. It is concluded that the phage therapy by using phage preparations as the 25 phages cocktail evaluated in this study is a highly promising and potential alternative therapy for human UTIs.


Expression and characterization of full-length human heme oxygenase-1: the presence of intact membrane-binding region leads to increased binding affinity for NADPH cytochrome P450 reductase.
Heme oxygenase-1 (HO-1) is the chief regulatory enzyme in the oxidative degradation of heme to biliverdin. In the process of heme degradation, HO-1 receives the electrons necessary for catalysis from the flavoprotein NADPH cytochrome P450 reductase (CPR), releasing free iron and carbon monoxide. Much of the recent research involving heme oxygenase has been done using a 30 kDa soluble form of the enzyme, which lacks the membrane binding region (C-terminal 23 amino acids). The goal of this study was to express and purify a full-length human HO-1 (hHO-1) protein; however, due to the lability of the full-length form, a rapid purification procedure was required. This was accomplished by use of a glutathione-s-transferase (GST)-tagged hHO-1 construct. Although the procedure permitted the generation of a full-length HO-1, this form was contaminated with a 30 kDa degradation product that could not be eliminated. Therefore, attempts were made to remove a putative secondary thrombin cleavage site by a conservative mutation of amino acid 254, which replaces arginine with lysine. This mutation allowed the expression and purification of a full-length hHO-1 protein. Unlike wild type (WT) HO-1, the R254K mutant could be purified to a single 32 kDa protein capable of degrading heme at the same rate as the WT enzyme. The R254K full-length form had a specific activity of approximately 200-225 nmol of bilirubin h-1 nmol-1 HO-1 as compared to approximately 140-150 nmol of bilirubin h-1 nmol-1 for the WT form, which contains the 30 kDa contaminant. This is a 2-3-fold increase from the previously reported soluble 30 kDa HO-1, suggesting that the C-terminal 23 amino acids are essential for maximal catalytic activity. Because the membrane-spanning domain is present, the full-length hHO-1 has the potential to incorporate into phospholipid membranes, which can be reconstituted at known concentrations, in combination with other endoplasmic reticulum resident enzymes.


A peptide derivative (1-70 fragment) of protein SV-IV accelerates human blood coagulation in vitro by selective inhibition of the heparin-induced antithrombin III activation process.
The effect of two peptide derivatives of the rat SV-IV (SV-IV/A: 1-70 fragment; SV-IV/B: 71-90 fragment) on human blood coagulation was investigated. The SV-IV/A fragment was found to possess the same procoagulant activity of the native protein, whereas SV-IV/B retained only a very small fraction of the activity. The results obtained strongly suggest that the procoagulant activity of SV-IV/A is due, like SV-IV, to a selective inhibition of the antithrombin III (AT III) activation process induced by heparin, an essential cofactor of AT III. The main data supporting this hypothesis are the following: 1) the concentration of active serum AT III decreases when SV-IV/A is present in the clotting system; 2) the plasma treatment with SV-IV/A reduces the concentration of AT III, but not that of other plasma serine protease inhibitors; 3) the recalcification time (RT) of the plasma treated with a rabbit anti-AT III polyclonal antiserum is not modified by SV-IV/A; 4) the presence of SV-IV/A in a reaction mixture containing pure fibrinogen, alpha-thrombin, heparin, and AT III neutralizes the thrombin inhibition induced by AT III; 5) the concentration of the thrombin-AT III complexes, occurring in sera obtained from CaCl2-coagulated plasma, is markedly reduced in the presence of SV-IV/A; 6) appropriate concentrations of heparin neutralize the inhibitory effect of either SV-IV/A or SV-IV on the AT III activity in vitro.


Pathological grief: diagnosis and explanation.
Pathological grief deserves a place in the diagnostic nomenclature. Because posttraumatic stress disorder requires an event beyond the range of usual experience and bereavement is virtually a universal experience, a new diagnosis of signs and symptoms precipitated by a loss event is needed. Many varieties of pathological grief have been noted in clinical research studies, and multiple diagnoses of pathological grief would make research difficult. The authors advance a solution in a personality-based explanation of abnormal responses to loss events; this allows for a single diagnosis of pathological grief. The authors also present a predictive model to partially explain pathological grief by antecedent trait combinations. The hypothesis is that persons with a preloss combination of both contradictions in relational schemas about the deceased and tendencies toward excessive control to stifle unwanted affect will tend to have unsuccessful processes of mourning. Types of contradictions and overcontrol may vary, yielding personality-based varieties of response within a single diagnostic category.


Positive effects of vegetable and fruit consumption and calcium intake on bone mineral accrual in boys during growth from childhood to adolescence: the University of Saskatchewan Pediatric Bone Mineral Accrual Study.
Nutrition is an important modifiable factor in the development of bone mass during adolescence. Recent studies of children and adolescents examined the effects of foods such as milk products and fruit and vegetables on bone growth; however, few studies included both boys and girls. The purpose was to ascertain the role of consumption of milk products and vegetables and fruit in the accrual of total-body bone mineral content (TBBMC) in boys and girls from childhood to late adolescence. Seven-year longitudinal data were obtained from 85 boys and 67 girls aged 8-20 y. Biological maturity was defined by the number of years from the age at peak height velocity. Dietary intake was assessed by serial 24-h recalls. Anthropometric measurements and physical activity were assessed every 6 mo. TBBMC assessed with dual-energy X-ray absorptiometry in the fall of each year was the indicator of bone mass. Most boys (87.8%) met Canadian recommendations for milk product intake. Few subjects (<30%) consumed vegetables and fruit in recommended amounts. Using a multilevel modeling statistical approach containing important biological and environmental factors, we found that vegetable and fruit intakes, calcium intake, and physical activity were significant independent environmental predictors of TBBMC in boys but not in girls. In addition to adequate dietary calcium intake, appropriate intakes of vegetables and fruit have a beneficial effect on TBBMC in boys aged 8-20 y. Underreporting of dietary intake by girls may explain why this effect was not apparent in girls.


A comparison of the effect of certain inorganic salts on suppression acute skin irritation by human biometric assay: A randomized, double-blind clinical trial.
Strontium, zinc, and potassium salts have been demonstrated to inhibit irritation and inflammation when applied topically. Particularly, strontium chloride (SC) and potassium nitrate (KN) are reported to reduce skin and tooth sensitivity. The aim of the present study was to compare the anti-irritant effects of four inorganic salts and assign the ingredient which can suppress skin irritation due to chemical or environmental exposure, more effectively. We compared the anti-inflammatory effects of SC, strontium nitrate (SN), KN, and zinc chloride (ZC). This double-blind trial was conducted on 32 healthy volunteers with sensitive skin. Irritation was induced by 24 h exposure with 1.0% sodium lauryl sulfate on arms. Treatments were applied by an ointment of SN, SC hexahydrate, KN, and ZC and their 1%, 3%, and 5% (w/v) concentrations were prepared. The dosage was twice daily for 6 days to the irritated areas. Skin reactions were evaluated instrumentally. SC had a beneficial effect that was significant overall. All other treatments exert a protective effect in skin barrier function but not significantly. With the exception of ZC, all test substances improved skin hydration but the effect of SC was significant. In respect of colorimetric assessment, all treatments, excluding ZC, reduced erythema significantly compared with an untreated control 7 days after treatment start. There was no support for a dose-response effect. Analysis of the biometric measurements revealed that the strontium salts are best, not treating is worst, and there is little difference between the other treatments. Hence, the skin care products containing SC and SN may reduce the signs and symptoms of irritant contact dermatitis.


A Hybrid Electrocatalyst with a Coordinatively Unsaturated Metal-Organic Framework Shell and Hollow Ni3S2/NiS Core for Oxygen Evolution Reaction Applications.
Metal-organic frameworks (MOFs) have emerged as a promising class of materials. However, their insulating nature has limited their application as electrocatalysts. Herein, we report a heterogeneous nanostructure of a Ni-based MOF-modified Ni3S2/NiS hollow nanoparticle. The Ni3S2/NiS hollow core is prepared by a sulfuration process from a colloidal nickel nanoparticle using dodecanethiol followed by a low-temperature heat treatment in air to remove the adsorbed organic ligands. The thin shell of the Ni-based MOF (Ni-BDC) is synthesized using an in situ method in which the nickel sulfides supply the metal source and the additional terephthalic acid serves as the linker. Serving as an oxygen evolution reaction catalyst, this hybrid nanocomposite shows superior electrocatalytic performance with a low overpotential of 298 mV at 10 mA·cm-2 without carbon addition and a long-time endurability with no detectable activity deterioration, which can be attributed to the synergistic effect of the advantageous heterogeneous structure, combining the good hydrophilicity and coordinative unsaturation of the Ni-BDC shell and the high conductivity and porosity of the Ni3S2/NiS core as well as the strongly coupled interface between them.


Eating behaviours of middle- and secondary-school pupils from the upper Silesian region in Poland.
Eating behaviours of school-aged youth condition their emotional and psychophysical development. Moreover, they influence the effectiveness of learning and affect one's health and the quality of life at older age. The objective of the study was the evaluation of eating behaviours of the group of pupils from cities of the Upper Silesian region, as well as the identification of differences between middle-school and secondary-school pupils' eating behaviours. 902 pupils (474 middle-school and 428 secondary-school pupils) participated in the study. The research materials included questionnaires prepared by the author of the study, containing the questions about the pupils' eating habits. The middle-school pupils constituted 52.5% of the 902 pupils and the secondary-school pupils were 47.5% of the total. On average, 38.2% of the pupils consumed 4 meals daily. Wholemeal bread and/or groats were eaten daily by 34.4% of the pupils. Milk and/or milk drinks were consumed by 56.3% of the pupils every day and 33.5% of the respondents had also fermented milk drinks daily. 61.3% of the participants declared eating meat at least once a day and 44.9% of the pupils had fish once or twice a week. Vegetables and fruit were eaten daily by 61.4% and 66.6% of the pupils respectively. Sweets were consumed at least once a day by 50.6% of the pupils. Occasional consumption of fast-food products and ready-made meals was declared by 63.9% and 49.7% of the pupils respectively. Eating behaviours of the discussed group of pupils are mostly incorrect. There were differences found between the middle-school and secondary-school pupils' eating habits. The differences concerned the frequency of eating cheese and curd cheese, fruit, leguminous plant seeds, sweets, fast food products, sweetened drinks and ready-to made food products. eating behaviours, eating habits, eating frequency, pupils.


COMPARATIVE ANALYSIS OF RETINAL REATTACHMENT SURGERY WITH OR WITHOUT INTERNAL LIMITING MEMBRANE PEELING TO PREVENT POSTOPERATIVE MACULAR PUCKER.
To determine whether internal limiting membrane (ILM) peeling during pars plana vitrectomy for rhegmatogenous retinal detachment reduces the incidence of epiretinal membrane (ERM) formation. In this retrospective study, preoperative, intraoperative, and postoperative data from all eyes undergoing pars plana vitrectomy for rhegmatogenous retinal detachment between January 2007 and December 2013 was analyzed. All cases with at least 1-year of follow-up were included. Data collection included vision, intraoperative complications, occurrence of ERM, and spectral domain optical coherence tomography characteristics. The OCTs were retrieved for all eyes and were graded by a single masked grader. Out of 159 eyes recruited, ILM peeling was done in 78 eyes (49%). Overall occurrence of ERM was 20%. Seven eyes (9%) in ILM peeling group and 25 eyes in the non-ILM peeling group (31%) showed ERM (P = 0.001). Postoperative vision was significantly better in eyes that had ILM peeling (0.48 ± 0.4 logarithm of the minimum angle of resolution [20/63] vs. 0.77 ± 0.6 logarithm of the minimum angle of resolution [20/125], P = 0.003). In multivariable models adjusting for type of tamponade, ILM peeling reduced the likelihood of ERM formation by 75% (P = 0.01). Internal limiting membrane peeling during pars plana vitrectomy for rhegmatogenous retinal detachment significantly reduces ERM formation in the postoperative period and is associated with better visual and anatomical outcomes.


Stair negotiation made easier using novel interactive energy-recycling assistive stairs.
Here we show that novel, energy-recycling stairs reduce the amount of work required for humans to both ascend and descend stairs. Our low-power, interactive, and modular steps can be placed on existing staircases, storing energy during stair descent and returning that energy to the user during stair ascent. Energy is recycled through event-triggered latching and unlatching of passive springs without the use of powered actuators. When ascending the energy-recycling stairs, naive users generated 17.4 ± 6.9% less positive work with their leading legs compared to conventional stairs, with the knee joint positive work reduced by 37.7 ± 10.5%. Users also generated 21.9 ± 17.8% less negative work with their trailing legs during stair descent, with ankle joint negative work reduced by 26.0 ± 15.9%. Our low-power energy-recycling stairs have the potential to assist people with mobility impairments during stair negotiation on existing staircases.


Mobile-bearing total knee arthroplasty: do the polyethylene bearings rotate?
In vivo kinematics were determined during a weightbearing deep knee bend in 39 patients implanted with four different designs of mobile-bearing total knee arthroplasty to assess polyethylene bearing mobility patterns and magnitudes. The femoral and tibial components and mobile polyethylene insert (implanted with four tantalum beads) were overlaid onto the fluoroscopic images using a three-dimensional model-fitting technique to determine bearing mobility. Three of the four designs were tested at a single time interval while one was evaluated at two postoperative intervals, (12 months apart) to assess changes in bearing mobility with time. All patients had polyethylene bearing rotation relative to the tibial tray and minimal rotation relative to the femoral component. The average maximum amounts of bearing rotation ranged from 8.4 degrees to 10.3 degrees (range, 3.0 degrees -20.1 degrees). In patients evaluated at two time intervals, the average maximum bearing rotation increased from 8.5 degrees (range, 3.4 degrees -15.5 degrees) at 3 months to 9.8 degrees (range, 48 degrees -14.1 degrees) 15 months postoperatively. The presented data demonstrates polyethylene bearing mobility occurs following mobile-bearing total knee arthroplasty and mobility is maintained during the time interval tested. The presence of bearing mobility should result in lower contact stresses reducing the potential for polyethylene wear.


Predictors of return to work for people on sick leave with depression, anxiety and stress: secondary analysis from a randomized controlled trial.
Knowledge about predictors of return to work (RTW) in people on sick leave with common mental disorders (CMDs) may inform the development of effective vocational rehabilitation interventions for this target group. In this study, we investigated predictors of RTW at 6 and 12 months in people on sick leave with depression, anxiety disorders or stress-related disorders. We have performed a secondary analysis, utilizing data from two RCTs that evaluated the efficacy of an integrated health care and vocational rehabilitation intervention. Data were obtained from mental health assessments, questionnaires and registers. Using Cox regression analysis, the relationship between baseline variables and RTW was analysed at 6 and 12 months after randomization within the group of CMD as a whole and within the subgroups of depression, anxiety and stress-related disorders. Symptom burden and employment status at baseline predicted RTW in the CMD group (n = 1245) and in the three diagnostic subgroups at both time points. RTW self-efficacy predicted RTW in the depression group but not in the anxiety or stress subgroups. Many predictors of RTW were similar over time and, to some extent, across the CMD subgroups. Findings highlight the need not only to take health-related and psychological factors into account when developing vocational rehabilitation interventions but also to consider workplace strategies and options for support.


Cryptodeterminant of a sperm maturation antigen on the mouse flagellar surface.
The determinant of a mouse sperm maturation antigen was examined morphologically and biochemically with monoclonal antibody T21 as a probe. The plasma membrane components of cauda epididymal spermatozoa were extracted with nonionic detergent Nonidet P-40 and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions and by immunoblotting. Wheat germ agglutinin-lectin staining and immunoblotting indicated that the antigen recognized by T21 is a sialoglycoprotein of about 54,000 daltons (54 kDa). The antigenic determinant was more distinctly exposed after treatment with neuraminidase, as evaluated by immunohistochemistry, immunocytochemistry, and immunoblotting. The cryptic nature of the determinant was further confirmed by immunostaining nitrocellulose strips, subsequently digesting the strips with neuraminidase, and then reimmunostaining them. Results obtained by periodate oxidation treatment suggested that the epitope is a carbohydrate. Immunoperoxidase electron microscopy confirmed that the antigen is distributed on the flagellar plasma membrane of the sperm. This was demonstrated clearly when sperm were desialylated with neuraminidase. These results indicate that the 54 kDa sialoglycoprotein sperm maturation antigen has a cryptodeterminant which can be masked by a sialic acid residue, that is recognized by monoclonal antibody T21.


Th17 cells are restrained by Treg cells via the inhibition of interleukin-6 in patients with rheumatoid arthritis responding to anti-tumor necrosis factor antibody therapy.
The importance of interleukin-17 (IL-17) is underscored both by its resistance to control by Treg cells and the propensity of Treg cells to produce this highly inflammatory cytokine. This study sought to address whether Th17 cells are inhibited by Treg cells in rheumatoid arthritis (RA) patients responding to anti-tumor necrosis factor (anti-TNF) therapy, and if so defining the underlying mechanisms of suppression. Inhibition of Th17 cell responses was determined by Treg cell suppression assays. The Treg cell phenotype was analyzed using flow cytometry and enzyme-linked immunosorbent assay. Mechanisms of suppression were tested by cytokine addition or antibody blockade. Th17 responses were inhibited by Treg cells from RA patients responding to the anti-TNF antibody adalimumab (Treg(ada) ), but not by Treg cells from healthy individuals or patients with active RA. Furthermore, Treg(ada) cells secreted less IL-17, even when exposed to proinflammatory monocytes from patients with active RA. Treg(ada) cells suppressed Th17 cells through the inhibition of monocyte-derived IL-6, but this effect was independent of IL-10 and transforming growth factor β, which mediated the suppression of Th1 responses. Adalimumab therapy led to a reduction in retinoic acid receptor-related orphan nuclear receptor C-positive Th17 cells and an increase in FoxP3+ Treg cells lacking expression of the transcription factor Helios. However, this acquisition of IL-17-suppressor function was not observed in RA patients responding to treatment with etanercept, a modified TNF receptor-Fc fusion protein. Indeed, there was no alteration in Treg cell number, function, or phenotype in etanercept-treated patients, and Th17 responses remained unchecked. Th1 and Th17 responses are controlled through distinct mechanisms by Treg cells from patients responding to anti-TNF antibody therapy. Adalimumab therapy, but not etanercept therapy, induces a potent and stable Treg cell population with the potential to restrain the progression of IL-17-associated inflammation in RA via regulation of monocyte-derived IL-6.


Prevalence of Vaping and Behavioral Associations of Vaping Among a Community of College Students in the United States.
We investigated the prevalence of vaping among college students in South-central Appalachia in the United States and explored factors which were associated with and could predict vaping among the college students. A sample of 498 enrolled students voluntarily completed a self-report REDCap health survey questionnaire in 2018. Outcome variable was use of electronic cigarettes categorized as yes/no. Independent variables included risky behaviors such as texting or emailing while driving, riding in a car with someone who had been drinking, history of protected and unprotected sexual intercourse, age at first intercourse, and type of contraceptive used. Covariates were age, gender, ethnicity/race and high school location. The first category was used as reference. Binary logistic regression was used to identify factors associated with and predicting vaping. Mean age of participants was 20.93(± 8.26), 62.9% were female, a majority (76.5%) were non-Hispanic White, and 43.2% reported vaping at some point in their lives. Initial univariate analysis showed gender (p < 0.0001), seat belt usage (p = 0.002), texting or emailing while driving (p = 0.002), riding in a car with someone who had been drinking (p = 0.001), history of sexual intercourse (p < 0.001), coitarche (p = 0.026), use of birth control pills and withdrawal method were associated with vaping. Adjusting for co-variates, gender (p < 0.002), county of high school (p < 0.009) and texting and e-mailing while driving (0.05), seat belt usage (0.04) remained significant. Vaping was highly prevalent (43.2%) among our participants. Gender, location of high school, texting/emailing while driving and seat belt usage are predictors of vaping among these students.


Preventing violence in developing countries: a framework for action.
Violence is an enormous global public health problem that increases the risk of injury, disease and poor mental health while also impeding economic and social development. This paper articulates a framework for violence prevention in developing countries that is grounded in the knowledge gained from research and programmatic efforts in rich and in poor countries over several decades. This framework can be used by countries and funding agencies as a guide to building strong foundations for ongoing violence prevention efforts and for identifying violence prevention strategies most likely to be effective. The world has learned a lot about preventing violence and, without a doubt, there is a great deal more to learn. As a global community, however, it is not possible to wait for perfect solutions to these problems to act. The obligation is to act now to use the valuable knowledge that has been gained about violence prevention to improve the world.


2,3,7,8-Tetrachlorodibenzo-p-dioxin suppresses tumor necrosis factor-alpha and anti-CD40-induced activation of NF-kappaB/Rel in dendritic cells: p50 homodimer activation is not affected.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) suppresses many immune responses, both innate and adaptive. Suppression is mediated by the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor. The AhR mediates TCDD toxicity presumably through the alteration of transcriptional events, either by promoting gene expression or potentially by physically interacting with other transcription factors. Another transcription factor, NF-kappaB/Rel, is involved in several signaling pathways in immune cells and is crucial for generating effective immune responses. Dendritic cells (DCs), considered to be the "pacemakers" of the immune system, were recently recognized as targets of TCDD and are also dependent on NF-kappaB/Rel for activation and survival. In these studies, we investigated whether TCDD would alter the activation of NF-kappaB/Rel in DCs. The dendritic cell line DC2.4 was exposed to TCDD before treatment with tumor necrosis factor alpha (TNF-alpha) or anti-CD40, and NF-kappaB/Rel activation was measured by electrophoretic mobility shift assay and immunoblotting. TCDD suppressed the binding of NF-kappaB/Rel to its cognate response element in TNF-alpha- and anti-CD40-treated cells and blocked translocation to the nucleus. The AhR was shown to associate with RelA, after coimmunoprecipitation, and seemed to block its binding to DNA. It is noteworthy that p50 homodimers freely bound to DNA. These results suggest that TCDD may alter the balance between NF-kappaB/Rel heterodimers and transcriptional inhibitory p50 homodimers in DCs, leading to defects in the DCs and suppression of the immune response.


Fibrillary glomerulonephritis in a human immunodeficiency virus-positive, hepatitis C-negative Indian patient: Expanding the profile of renal involvement in human immunodeficiency virus infection.
Highly active anti retroviral therapy (HAART) has dramatically improved life expectancy of human immunodeficiency virus (HIV) infected patients, converting HIV infection into a chronic illness with associated changes in its attendant renal complications. The past two decades have witnessed a decrease in the prevalence of HIV associated nephropathy (HIVAN), traditionally considered to be the hall mark of renal involvement in HIV infection. Simultaneously a host of other glomerular and tubulo-interstitial diseases have emerged, expanding the spectrum of HIV associated renal diseases, predominant among which is HIV associated immune complex mediated kidney diseases (HIVICK). Of the diverse glomerular diseases constituting HIVICK, fibrillary glomerulonephritis (FGN) remains a rarity, with only two existing reports to date, confined to patients co-infected with Hepatitis C virus (HCV). The pathogenetic role of HIV in these patients remains under a cloud because of previously well established association of HCV infection and FGN. We report a case of FGN in a HIV seropositive, HCV negative Indian patient, highlighting the diagnostic electron microscopy (EM) findings of FGN and strengthening the causal association of HIV with FGN. In view of increasing heterogeneity of renal complications in HIV infection, the diagnostic utility of a comprehensive renal biopsy evaluation inclusive of EM is emphasized for appropriate selection of treatment modalities.


Protective effect of dietary tender cluster beans (Cyamopsis tetragonoloba) in the gastrointestinal tract of experimental rats.
In this study, the gastrointestinal protective effect of soluble, dietary fiber-rich tender cluster beans, with respect to the activities of antioxidant enzymes and the concentration of antioxidant molecules, was examined in Wistar rats. Dietary intervention with tender cluster beans (15% freeze-dried powder in the diet for 8 weeks) significantly enhanced the activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione reductase, glutathione-S-transferase, and GPX) and the concentrations of antioxidant molecules in both gastric and intestinal mucosa. Further, in combination with capsaicin (0.01%), the beneficial effect was even higher. There is a strong indication that tender cluster beans offer a significant gastroprotective effect, and a much greater effect when combined with capsaicin in terms of increased antioxidant status. In a separate study, these dietary components were found to alleviate the diminished activities of antioxidant enzymes and antioxidant molecules in gastric and intestinal mucosa under conditions of ethanol-induced oxidative stress. The gastroprotective effect of the cluster bean was also reflected in its positive effect on gastric mucosal glycoproteins, resulting in a lowering of mucosal injury. Incidentally, the serum and liver also showed an elevated antioxidant status, thus suggesting desirable lowered oxidative stress results when tender cluster beans are consumed.


Neonatal screening for congenital adrenal hyperplasia in Japan.
A nationwide screening test for congenital adrenal hyperplasia (CAH) was first initiated in Japan in 1989, over 20 years ago, and it is now 30 years since a pilot study was initiated in Sapporo in 1982. The incidence of 21-hydroxylase deficiency in Japan is about 1/18,000 persons, which is similar to that in other countries. The effectiveness of early detection and treatment of CAH in Japan has been demonstrated by cost-benefit analyses. However, the false-positive rate of CAH screening in preterm infants remains high compared to screening tests for term infants. To improve the positive predictive value, we have employed 21-hydroxylase gene (CYP21A2) analysis on dried blood spots and high performance liquid chromatography (HPLC) to measure 17-hydroxyprogesterone, and currently use tandem mass spectrometry (LC-MS/MS) as a screening technique. We suggest that LC-MS/MS should be used in the future to improve the accuracy of CAH screening in Japan.


Inbreeding depression in line 1 Hereford cattle population using pedigree and genomic information.
This study aimed at assessing inbreeding and its effect on growth and fertility traits using the longtime closed line 1 Hereford cattle population. Inbreeding was estimated based on pedigree (FPED) and genomic information. For the latter, three estimates were derived based on the diagonal elements of the genomic relationship matrix using estimated (FGRM) or fixed (FGRM0.5) minor allele frequencies or runs of homozygosity (ROH) (FROH). A pedigree containing 10,186 animals was used to calculate FPED. Genomic inbreeding was evaluated using 785 animals genotyped for 30,810 SNP. Traits analyzed were birth weight (BWT), weaning weight (WWT), yearling weight (YWT), ADG, and age at first calving (AFC). The number of ROH per animal ranged between 6 and 119 segments with an average of 83. The shortest and longest segments were 1.36 and 64.86 Mb long, respectively, reflecting both ancient and recent inbreeding occurring in the last 30 to 40 generations. The average inbreeding was 29.2%, 16.1%, 30.2%, and 22.9% for FPED, FGRM, FGRM0.5, and FROH, respectively. FROH provided the highest correlations with FPED (r = 0.66). Across paternal half-sib families, with minimal variation in FPED, there were substantial variations in their genomic inbreeding. Inbreeding depression analyses showed that a 1% increase in an animal's FPED resulted in a decrease of 1.20 kg, 2.03 kg, and 0.004 kg/d in WWT, YWT, and ADG, respectively. Maternal inbreeding showed significantly negative effects on progeny growth performance. AFC increased by 1.4 and 0.8 d for each 1% increase in FPED of the cow and her dam, respectively. Using genomic inbreeding, similar impact on growth traits was observed although the magnitude of the effect varied between methods. Across all genomic measures, WWT, YWT, and ADG decreased by 0.21 to 0.53 kg, 0.46 to 1.13 kg, and 0.002 to 0.006 kg/d for each 1% increase in genomic inbreeding, respectively. Four chromosomes (9, 12, 17, and 27) were identified to have a significant association between their homozygosity (FROH-CHR) and growth traits. Variability in genomic inbreeding could be useful when deciding between full and half-sib selection candidates. Despite the high level of inbreeding in this study, its negative impact on growth performance was not as severe as expected, which may be attributed to the purging of the deleterious alleles due to natural or artificial selection over time.


Unperturbed hydrocarbon chains and liquid phase bilayer lipid chains: a computer simulation study.
In this work, the properties of saturated and unsaturated fatty acid acyl chains 16:0, 18:0, 18:1(n-9)cis, 18:2(n-6)cis, 18:3(n-3)cis, 18:4(n-3)cis, 18:5(n-3)cis, 20:4(n-6)cis, 20:5(n-3)cis and 22:6(n-3)cis in a bilayer liquid crystalline state and similar hydrocarbon chains (with CH[Formula: see text] terminal groups instead of C=O groups) in the unperturbed state characterised by a lack of long-range interaction were investigated. The unperturbed hydrocarbon chains were modelled by Monte Carlo simulations at temperature [Formula: see text] K; sixteen fully hydrated homogeneous liquid crystalline phosphatidylcholine bilayers containing these chains were studied by molecular dynamics simulations at the same temperature. To eliminate effects of the simulation parameters, the molecular dynamics and Monte Carlo simulations were carried out using the same structural data and force field coefficients. From these computer simulations, the average distances between terminal carbon atoms of the chains (end-to-end distances) were calculated and compared. The trends in the end-to-end distances obtained for the unperturbed chains were found to be qualitatively similar to those obtained for the same lipid chains in the bilayers. So, for understanding of a number of processes in biological membranes (e.g., changes in fatty acid composition caused by environmental changes such as temperature and pressure), it is possible to use, at least as a first approximation, the relationships between the structure and properties for unperturbed or isolated hydrocarbon chains.


Immune suppressive activity of the influenza fusion peptide.
Immune suppressive domains have been identified in retro and filoviral fusion proteins. Such domains constitute small peptide motifs that are evolutionarily very well preserved within each group. We here test the hypothesis that such preservation reflects a dual selection pressure for both immune suppression and membrane fusion activity in influenza viruses for which no immune suppressive peptide motifs have been identified. We identified a conserved motif in the fusion peptide of influenza hemagglutinin as a candidate for an immune suppressive domain using comparative and phylogenetic analysis. This peptide was indeed found to exhibit immune suppressive activity in several in vitro assays. Similar to the previously reported peptides from retro and filoviruses the influenza peptide had immune suppressive activity when presented as a dimer but not as a monomer.


Variation in nitrogen partitioning and reproductive stage nitrogen remobilization determines nitrogen grain production efficiency (NUEg) in diverse rice genotypes under varying nitrogen supply.
Nitrogen (N) is an important macronutrient needed for grain yield, grain N and grain protein content in rice. Grain yield and quality are significantly determined by N availability. In this study, to understand the mechanisms associated with reproductive stage N remobilization and N partitioning to grain 2 years of field experiments were conducted with 30 diverse rice genotypes during 2019-Kharif and 2020-Kharif seasons. The experiments were conducted with two different N treatments; N deficient (N0-no external N application, available soil N; 2019-234.15 kgha-1, 2020-225.79 kgha-1) and N sufficient (N120-120 kgha-1 external N application, available soil N; 2019-363.77 kgha-1, 2020-367.95 kgha-1). N application increased the NDVI value, biomass accumulation, grain yield, harvest index and grain N accumulation. Post-anthesis N uptake and N remobilization from vegetative tissues to grain are critical for grain yield and N harvest index. Rice genotypes, Kalinga-1, BAM-4234, IR-8384-B-B102-3, Sahbhagi Dhan, BVD-109 and Nerica-L-42 showed a higher rate of N remobilization under N sufficient conditions. But, under N deficiency, rice genotypes-83929-B-B-291-3-1-1, BVD-109, IR-8384-B-B102-3 and BAM-4234 performed well showing higher N remobilization efficiency. The total amount of N remobilization was recorded to be high in the N120 treatment. The harvest index was higher in N120 during both the cropping seasons. RANBIR BASMATI, BAM-832, APO, BAM-247, IR-64, Vandana, and Nerica-L-44 were more efficient in N grain production efficiency under N deficient conditions. From this study, it is evident that higher grain N accumulation is not always associated with higher yield. IR-83929-B-B-291-3-1-1, Kalinga-1, APO, Pusa Basmati-1, and Nerica-L-44 performed well for different N use efficiency component traits under both N deficient (N0) and N sufficient (N120) conditions. Identifying genotypes/donors for N use efficiency-component traits is crucial in improving the fertilizer N recovery rate and site specific N management.


Mother-perceived social capital and children's oral health and use of dental care in the United States.
We examined the association between mother-perceived neighborhood social capital and oral health status and dental care use in US children. We analyzed data for 67 388 children whose mothers participated in the 2007 National Survey of Children's Health. We measured mothers' perceived social capital with a 4-item social capital index (SCI) that captures reciprocal help, support, and trust in the neighborhood. Dependent variables were mother-perceived ratings of their child's oral health, unmet dental care needs, and lack of a previous-year preventive dental visit. We performed bivariate and multivariable logistic regression analyses for each outcome. After we controlled for potential confounders, children of mothers with high (SCI = 5-7) and lower levels (SCI ≥ 8) of social capital were 15% (P = .05) and about 40% (P ≤ .02), respectively, more likely to forgo preventive dental visits than were children of mothers with the highest social capital (SCI = 4). Mothers with the lowest SCI were 79% more likely to report unmet dental care needs for their children than were mothers with highest SCI (P = .01). A better understanding of social capital's effects on children's oral health risks may help address oral health disparities.


Arterial ligation in epistaxis.
Unremitting severe nose bleeds may require arterial ligation. One or more of the four vascular systems supplying the nose may need such surgical interference. Dye injection of 14 cadavers was performed to demonstrate the vascular supply of the nose and the effects of various arterial ligations. Depending upon the site of haemorrhage within the nose, up to three vascular systems may need occlusion. These are the ipsilateral and contralateral external carotid arterial systems and the ipsilateral ethmoidal arteries.


Hot spots on liver scans associated with superior or inferior vena caval obstruction.
Although hot spots on hepatic scintigrams have been reported in association with superior and inferior vena caval obstruction, these studies were not clinically correlated, and are hampered by the poor resolution of earlier scintillation cameras. In this report, a modern scintillation camera was used to study the formation of hot spots associated with superior and inferior vena caval obstruction. Moreover, radionuclide cavography was performed in 70 patients with superior vena caval (SVC) obstruction and in 95 patients with inferior vena caval (IVC) obstruction. As a result, 13 cases of hot spots in the liver were observed. In cases of SVC obstruction, hot spots were seen in the quadrate lobe, the medial segment, and the bare area of the liver. In IVC obstruction, a hot spot was seen in the quadrate lobe in all cases. In rare instances, in cases of both SVC and IVC obstruction, a hot spot was seen in the wide area. For these hot spots to develop, it appears necessary to have systemic-portal venous blood flow through the internal thoracic vein and the paraumbilical vein.


Long-Term Clinical and Neuronuclear Imaging Sequelae of Cancer Therapy, Trauma, and Brain Injury.
Neuronuclear imaging has been used for several decades in the study of primary neurodegenerative conditions, such as dementia and parkinsonian syndromes, both for research and for clinical purposes. There has been a relative paucity of applications of neuronuclear imaging to evaluate nonneurodegenerative conditions that can also have long-term effects on cognition and function. This article summarizes clinical and imaging aspects of 3 such conditions that have garnered considerable attention in recent years: cancer- and chemotherapy-related cognitive impairment, posttraumatic stress disorder, and traumatic brain injury. Further, we describe current research using neuroimaging tools aimed to better understand the relationships between the clinical presentations and brain structure and function in these conditions.


High-density-lipoprotein cholesterol in bodybuilders v powerlifters. Negative effects of androgen use.
To determine the relationship between lipid profiles and the type of weight training and to assess the effects of anabolic-androgenic steroids on lipids, bodybuilders and powerlifters of similar age, body fat, and testosterone levels were studied before and after androgen use. Before androgen administration powerlifters had lower levels of plasma high-density-lipoprotein cholesterol (HDL-C) and HDL2-C (38 +/- 2; 6 +/- 1 mg/dL; means +/- SE, n = 8) than bodybuilders (55 +/- 2; 12 +/- 1 mg/dL; n = 8) and runners of comparable age and body fat (47 +/- 2; 14 +/- 2 mg/dL; n = 8), while levels of low-density-lipoprotein cholesterol (LDL-C) were higher in powerlifters (138 +/- 10 mg/dL) than in bodybuilders (104 +/- 7 mg/dL) and runners (110 +/- 6 mg/dL). Therefore, powerlifters had higher LDL-C/HDL-C ratios (3.7 +/- 0.3) than bodybuilders (2.0 +/- 0.2) and runners (2.4 +/- 0.2). Androgen use by eight bodybuilders and four powerlifters lowered values of both HDL-C and HDL2-C by 55% and raised values of LDL-C (61% +/- 10%) and LDL-C/HDL-C ratios (280% +/- 40%). Therefore, the training regimen of bodybuilders is associated with a more favorable lipid profile than the training used by powerlifters. Androgen use by strength-trained athletes may increase their risk for coronary heart disease.


[Amnesic syndrome following lesion of the fornix or does reversible Korsakow's syndrome exist?].
The 53-year-old female patient had suffered massive subarachnoid bleeding due to rupture of left-localized aneurysm of the anterior communicant artery. Following the neurosurgical intervention, deterioration of consciousness related to strong vasospasm occurred. Cerebral CT examination was performed, showing a 0.5 cm ischaemic lesion of the left hippocampal fornix. Due to intensive therapy, the patient recovered gradually, however considerable short-time memory deficit and severe anterograde amnesia remained. Admission of the patient in psychiatric care 5 weeks after the operation was necessary since acute deterioration had been added to memory disturbance and anterograde amnesia. Clinical features included severe short-time memory deficit, continuous and severe anterograde amnesia, disorientation, alterations of verbal fluency and abstraction. The amnesic syndrome was probably related to the hippocampal damage, but considering the development of cognitive deficits, cerebral CT was performed again, which verified internal hydrocephalus. A ventriculo-peritoneal shunt has been implanted and the patient was re-admitted in psychiatry care because of her memory deficit, anterograde amnesia and disorientation. Thereafter, low doses of citalopram and donepezil therapy was started together with temporarily used antipsychotic medication (risperidone). Gradual, but continuous improvement of memory and cognitive function could be detected, with total recovery after one year. The deficits in long- and short-term memory, orientation and cognition were totally restored.


How can immunochemical methods contribute to the implementation of the Water Framework Directive?
Immunochemical methods (in particular immunoassays) have been applied to spring and surface water samples, respectively, which were set-up as reference materials (RM) within two proficiency testing campaigns. For the first set of proficiency tests (PTs) described here (which were actually the second round of PTs organized, spring 2005), three ELISAs (enzyme-linked immunosorbent assays) were employed in the enzyme tracer format for isoproturon, diuron, and atrazine, respectively. Results were evaluated in comparison with conventional reference methods (LC, GC). Based on their Z-score laboratory performances, the results for isoproturon and diuron were satisfactory, both for fortified spring water and for the blind solution. The results for atrazine were strongly influenced by other triazines present and needed detailed interpretation. For the second set of PTs described here (which were actually the third round of PTs organized, spring 2006), two ELISAs in the coating antigen format were used for isoproturon and diuron, and the result was included with the results obtained by conventional methods during the PTs. The results (the Z-scores) for isoproturon were again classified as satisfactory, in both fortified surface water and blind solution. The results for diuron in ELISA showed an influence of the water matrix, while the analysis of the blind solution was satisfactory. In addition, an ELISA in the enzyme tracer format was applied to analyze isoproturon, diuron, and atrazine in surface water samples, which had been set-up and spiked during a field trial (tank experiment) at the Maas River at Eijsden, The Netherlands. The immunoassay results were compared with those from an in-house on-line SPE LC/MS-MS used as reference. Although the immunochemical results were sometimes higher than those determined in the reference analysis, the general concentration trends in the samples were similar. The contribution of immunochemical methods to the implementation of the European Water Framework Directive is also discussed.


The efficacy of an educational treatment program for patients with epilepsy (MOSES): results of a controlled, randomized study. Modular Service Package Epilepsy.
To evaluate the efficacy of the educational program MOSES (Modular Service Package Epilepsy). It was developed to improve patients' knowledge and understanding about their epilepsy, its treatment, and psychosocial consequences. The program intends to improve patients' coping with the disease, to strengthen self-esteem, and to support patients to become experts in managing their epilepsy. A controlled, randomized study design was used to examine the efficacy of MOSES. Patients from 22 epilepsy centers in Germany, Austria, and Switzerland were randomly allocated to either MOSES group (treatment group) or waiting-list group (control group). The 242 patients were aged from 16 to 80 years. The MOSES group (n = 113) completed the questionnaires immediately before the educational course (T1) and 6 months later (T2), and the control group (n = 129), 6 months before (T1) and immediately before (T2) the course. The questionnaires included generic instruments (SF-36, Rosenberg self-esteem Scale, von Zerssen Depression Scale), and epilepsy-specific scales (Restrictions in Daily Life, Epilepsy-Related Fears, Coping with Epilepsy and Adaptation). Depression was used as a moderator variable. Seizure frequency and satisfaction with therapy also were assessed. Multivariate analysis of variance (MANOVA) with repeated measurements and univariate analyses of variance were performed. The MANOVA showed that participants of the educational program improved significantly. Univariate analyses revealed improvements in knowledge (p < 0.001) and coping with epilepsy (p = 0.004), whereas important effects of MOSES on other epilepsy-specific measures and on generic questionnaires (SF-36, self-esteem) were not found. Participants of the MOSES program also improved in seizure outcome (p = 0.041) and became more satisfied with the therapy [better tolerability of antiepileptic drug (AED) therapy, fewer side effects; p = 0.014]. In addition, participants expressed being highly satisfied with the program. The study clearly indicates the need for patient education. Even patients with a long history of epilepsy and with additional handicaps or diseases benefitted from the MOSES program.


Inhibitory effects of 6-alkoxycoumarin and 7-alkoxycoumarin derivatives on lipopolysaccharide/interferon γ-stimulated nitric oxide production in RAW264 cells.
Coumarin and its derivatives are well known for their anti-inflammatory and anti-oxidative effects. In this study, we synthesized 32 coumarin derivatives from commercially available 6-hydroxycoumarin (6HC) and 7-hydroxycoumarin (7HC) and examined their effects on lipopolysaccharide/interferon γ (LPS/IFNγ)-stimulated nitric oxide (NO) production in murine macrophage RAW264 cells. Among these derivatives, 6HC-8 (6-(3-phenylpropoxy)coumarin), 6HC-14 (6-(2-octynyloxy)coumarin), 7HC-14 (7-(2-octynyloxy)coumarin), and 7HC-16 (7-(3,5-dimethoxybenzyloxy)coumarin) markedly suppressed NO production at low concentration (25 µM). These synthesized coumarin derivatives also markedly inhibited inducible NO synthase (iNOS) protein and mRNA expression, as assessed by western blotting and quantitative real time-polymerase chain reaction (RT-PCR).


The liver stage of Plasmodium berghei inhibits host cell apoptosis.
Plasmodium berghei is the causative agent of rodent malaria and is widely used as a model system to study the liver stage of Plasmodium parasites. The entry of P. berghei sporozoites into hepatocytes has extensively been studied, but little is known about parasite-host interaction during later developmental stages of the intracellular parasite. Growth of the parasite far beyond the normal size of the host cell is an important stress factor for the infected cell. Cell stress is known to trigger programmed cell death (apoptosis) and we examined several apoptotic markers in P. berghei-infected cells and compared their level of expression and their distribution to that of non-infected cells. As none of the apoptotic markers investigated were found altered in infected cells, we hypothesized that parasite infection might confer resistance to apoptosis of the host cell. Treatment with peroxide or serum deprivation induced apoptosis in non-infected HepG2 cells, whereas P. berghei-infected cells appeared protected, indicating that the parasite interferes indeed with the apoptotic machinery of the host cell. To prove the physiological relevance of these results, mice were infected with high numbers of P. berghei sporozoites and treated with tumour necrosis factor (TNF)-alpha/D-galactosamine to induce massive liver apoptosis. Liver sections of these mice, stained for degraded DNA, confirmed that infected cells containing viable parasites were protected from programmed cell death. However, in non-treated control mice as well as in TNF-alpha-treated mice a small proportion of dead intracellular parasites with degraded DNA were detected. Most hepatocytes containing dead parasites provoked an infiltration of immunocompetent cells, indicating that these cells are no longer protected from cell death.


Nonrandom distribution of N-myc oncogene genotypes in neuroblastoma.
The distributions of Pvu II and Sph I alleles of the N-myc oncogene (also known as MYCN) were studied in a series of normal individuals and pediatric patients with solid tumors. In the case of Pvu II, where the polymorphic site is located 3' of the gene, the frequencies of the allele were 0.27 (11-kilobase fragment) and 0.73 (8-kilobase fragment) in 43 unrelated normal Caucasians. The frequencies of the allele were similar in 40 non-N-myc-amplified neuroblastomas, 47 Wilms' tumors, and 31 other pediatric tumors. In these cases, the genotypes were in Hardy-Weinberg equilibrium. In 18 N-myc-amplified neuroblastomas, however, the observed genotype frequencies deviated from Hardy-Weinberg equilibrium (P less than .005). Similar observations were made with an Sph I restriction fragment length polymorphism where the polymorphic site is located in intron 2. The differences between amplified and nonamplified neuroblastomas suggest a possible involvement of sequences at or near N-myc in the progression of tumors where the N-myc gene is amplified.


Tension-free repair versus watchful waiting for men with asymptomatic or minimally symptomatic inguinal hernias: a cost-effectiveness analysis.
Watchful waiting (WW) has been shown to be an acceptable option in men with asymptomatic or minimally symptomatic inguinal hernias when clinical and patient-reported outcomes are considered. Although WW is likely to be less costly initially when compared with tension-free repair (TFR) because of the cost of the operation, it is not clear whether WW remains the least costly option when longer-term costs are considered. We conducted a cost-effectiveness analysis of a randomized controlled trial at six community and academic centers. We examined costs, quality-adjusted life-years (QALY), and cost-effectiveness at 2 years of followup. Costs were assessed by applying Medicare reimbursement rates to patients' health-care use, which was obtained by contacting patients' health-care providers. Quality of life was assessed using the Short Form-36 version 2 health-related quality-of-life survey. Of the 724 men randomized, 641 were available for the economic analysis: 317 were randomized to TFR and 324 were randomized to watchful waiting. At 2 years, TFR patients had $1,831 higher mean costs than WW patients (95% CI, $409-$3,044), with 0.031 higher QALY (95% CI, 0.001-0.058). The cost per additional QALY for TFR patients was $59,065 (95% CI, $1,358-$322,765). The probability that TFR was cost-effective at the $50,000 per QALY level was 40%. At 2 years, WW was a cost-effective treatment option for men with minimal or no hernia symptoms.


Evaluation of the Diagnostic Performance of F18-Fluorodeoxyglucose-Positron Emission Tomography, Dynamic Susceptibility Contrast Perfusion, and Apparent Diffusion Coefficient in Differentiation between Recurrence of a High-grade Glioma and Radiation Necrosis.
Differentiation between recurrence of brain tumor and radiation necrosis remains a challenge in current neuro-oncology practice despite recent advances in both radiological and nuclear medicine techniques. The purpose of this study was to compare the diagnostic performance of dynamic susceptibility contrast (DSC) perfusion magnetic resonance imaging (MRI), apparent diffusion coefficient (ADC) derived from diffusion-weighted imaging, and F18-fluorodeoxyglucose-positron emission tomography (F18-FDG-PET) in the differentiation between the recurrence of a high-grade glioma and radiation necrosis. Patients with a diagnosis of high-grade glioma (WHO Grades III and IV) who had undergone surgical resection of the tumor followed by radiotherapy with or without chemotherapy were included in the study. DSC perfusion, diffusion-weighted MRI, and PET scan were acquired on a hybrid PET/MRI scanner. For each lesion, early and delayed tumor-to-brain ratio (TBR), early and delayed maximum standardized uptake value (SUVmax), normalized ADC ratio, and normalized relative cerebral blood volume (rCBV) ratio were calculated and the pattern of lesional enhancement was noted. The diagnosis was finalized with either histopathological examination or the characteristics on follow-up imaging. The statistical analysis using the receiver operator characteristic curves was done to determine the diagnostic performance of DSC perfusion, 18-F FDG-PET, and ADC in differentiation between tumor recurrence and radiation necrosis. Fifty patients were included in the final analysis, 32 of them being men (64%). A cutoff value of early TBR >0.8 (sensitivity of 100% and specificity of 80%), delayed TBR >0.93 (sensitivity of 92.3% and specificity of 80%), early SUVmax >10.2 (sensitivity of 76.9% and specificity of 80%), delayed SUVmax >13.2 (sensitivity of 61.54% and specificity of 100%), normalized rCBV ratio >1.21 (sensitivity of 100% and specificity of 60%), normalized ADC ratio >1.66 (sensitivity of 38.5% and specificity of 80%), and Grade 3 enhancement (sensitivity of 100% and specificity of 60%) were found to differentiate recurrence from radiation necrosis. Early TBR had the highest accuracy (94.44%), while ADC ratio had the lowest accuracy (50%). A combination of early TBR (cutoff value of 0.8), late TBR (cutoff value of 0.93), and rCBV ratio (cutoff value of 1.21) showed a sensitivity of 100%, specificity of 92.3%, positive predictive value of 88.9%, negative predictive value of 93.7%, and an accuracy of 96.6% in discrimination between radiation necrosis and recurrence of tumor. F18-FDG-PET and DSC perfusion can reliably differentiate tumor recurrence from radiation necrosis, with early TBR showing the highest accuracy. ADC demonstrates a low sensitivity, specificity, and accuracy in differentiating radiation necrosis from recurrence. A combination of early TBR, delayed TBR, and rCBV may be more useful in discrimination between radiation necrosis and recurrence of glioma, with this combination showing a better diagnostic performance than individual parameters or any other combination of parameters.


Secondary structure of the nascent 7S L RNA mediates efficient transcription by RNA polymerase III.
A structural motif at the 5' end of human 7S L (srp) RNA that is recognized specifically by cellular proteins has been identified as an efficient activator of RNA polymerase (pol) III transcription in vivo and in vitro. Mutations affecting three double-stranded regions or a tetranucleotide bulge of this RNA motif result in strongly reduced expression rates. However, effective suppression is achieved by compensatory mutations restoring RNA sequence complementarity. This activation of transcription is also observed in the context of another pol III promoter and is position-dependent. The effects observed are reminiscent of the Tat-TAR trans-activation of the human immunodeficiency virus and attribute a novel function to the structure of cellular small stable RNA.


The political and policy implications of a rating system of community capacity to improve population health.
This article discusses the political and policy implications of a potential rating system of community capacity for health improvement. Evidence suggests that such a rating system will have little effect in the current health care environment unless it is directly related to the health care dollar. Community change agents and stakeholders, including the growing population of older adults, will perceive a rating system to have value only if the defined purpose meets their interests and needs, and if the rating system results prove useful for decisions that affect the bottom line in working on issues like health improvement and capacity.


The role of adult attachment security in non-romantic, non-attachment-related first interactions between same-sex strangers.
Research using the Adult Attachment Interview has largely examined its predictive significance for interpersonal behavior within the context of observations of parent-child and romantic relationships. A limitation of this state of affairs is that the literature does not make clear whether or when attachment-related variation becomes reflected in other kinds of interpersonal encounters. This study demonstrates that links between adults' states of mind regarding childhood attachment experiences and the quality of their interpersonal interactions are evident in first meetings between same-sex strangers in a non-attachment-related context. More specifically, in a study of 50 stranger dyads (50% female), secure adults demonstrated positive emotional engagement during a challenging puzzle-building task. In contrast, preoccupied adults dominated the task, whereas dismissing adults evidenced negative emotion during the interaction. Results held controlling for the Big Five personality dimensions and suggest a middle ground position regarding the narrow versus broad correlates of adult attachment security.


Two group I mitochondrial introns in the cob-box and coxI genes require the same MRS1/PET157 nuclear gene product for splicing.
We have studied the role of the product of the nuclear gene PET157 in mitochondrial pre-mRNA splicing. Cytoduction experiments show that a mitochondrial genome deleted for the three introns bI3, aI5 and aI6 is able to suppress the pet157-1 mutation: the strain recovers respiratory competency indicating that the product of the PET157 gene is only required for mitochondrial pre-mRNA splicing. Characterization of the high molecular weight pre-mRNAs which accumulate in the pet157 mutant demonstrate that the product of the PET157 gene is required for the excision of two group I introns bI3 and aI6 (corresponding to aI5 beta) located in the cob-box and coxI genes respectively. Furthermore, the pet157 mutant strain accumulates the bI3 maturase in the form of a polypeptide of 50K (p50) previously observed in mitochondrial mutants defective in the excision of bI3. We have shown by restriction analysis and allelism tests that the pet157-1 mutation is allelic to the nuclear mrs1 mutation, previously described as specifically blocking the excision of bI3. Finally, revertants obtained by the deletion of bI3 or aI6 from the mitochondrial DNA were isolated from the MRS1 disrupted allele, confirming the involvement of the product of the MRS1/PET157 gene in the excision of the two introns bI3 and aI6.


Optic neuritis heralding varicella zoster virus retinitis in a patient with acquired immunodeficiency syndrome.
We report on a 29-year-old severely compromised acquired immunodeficiency syndrome patient who developed retrobulbar optic neuritis 5 weeks after an episode of cutaneous herpes zoster infection. During the optic neuritis, varicella zoster virus could be demonstrated in the cerebrospinal fluid. The neuritis responded well to treatment with foscarnet, but, 3 weeks into therapy, varicella zoster retinitis developed. Additional treatment with intravenous acyclovir stopped progression of the retinitis and resulted in healing of the retinal lesions. This case suggests that retrobulbar optic neuritis can be regarded as a prodrome of imminent acute retinal necrosis. Early recognition and prompt therapy with combined antivirals may prevent the development of this devastating ocular complication of varicella zoster infection.


An IL-4/IL-13 dual antagonist reduces lung inflammation, airway hyperresponsiveness, and IgE production in mice.
IL-4 and IL-13 comprise promising targets for therapeutic interventions in asthma and other Th2-associated diseases, but agents targeting either IL-4 or IL-13 alone have shown limited efficacy in human clinical studies. Because these cytokines may involve redundant function, dual targeting holds promise for achieving greater efficacy. We describe a bifunctional therapeutic targeting IL-4 and IL-13, developed by a combination of specific binding domains. IL-4-targeted and IL-13-targeted single chain variable fragments were joined in an optimal configuration, using appropriate linker regions on a novel protein scaffold. The bifunctional IL-4/IL-13 antagonist displayed high affinity for both cytokines. It was a potent and efficient neutralizer of both murine IL-4 and murine IL-13 bioactivity in cytokine-responsive Ba/F3 cells, and exhibited a half-life of approximately 4.7 days in mice. In a murine model of ovalbumin-induced ear swelling, the bifunctional molecule blocked both the IL-4/IL-13-dependent early-phase response and the IL-4-dependent late-phase response. In the ovalbumin-induced lung inflammation model, the bifunctional IL-4/IL-13 antagonist reduced the IL-4-dependent rise in serum IgE titers, and reduced IL-13-dependent airway hyperresponsiveness, lung inflammation, mucin gene expression, and serum chitinase responses. Taken together, these findings demonstrate the effective dual blockade of IL-4 and IL-13 with a single agent, which resulted in the modulation of a more extensive range of endpoints than could be achieved by targeting either cytokine alone.


Laplacian Eigenmaps Network-Based Nonlocal Means Method for MR Image Denoising.
Magnetic resonance (MR) images are often corrupted by Rician noise which degrades the accuracy of image-based diagnosis tasks. The nonlocal means (NLM) method is a representative filter in denoising MR images due to its competitive denoising performance. However, the existing NLM methods usually exploit the gray-level information or hand-crafted features to evaluate the similarity between image patches, which is disadvantageous for preserving the image details while smoothing out noise. In this paper, an improved nonlocal means method is proposed for removing Rician noise in MR images by using the refined similarity measures. The proposed method firstly extracts the intrinsic features from the pre-denoised image using a shallow convolutional neural network named Laplacian eigenmaps network (LEPNet). Then, the extracted features are used for computing the similarity in the NLM method to produce the denoised image. Finally, the method noise of the denoised image is utilized to further improve the denoising performance. Specifically, the LEPNet model is composed of two cascaded convolutional layers and a nonlinear output layer, in which the Laplacian eigenmaps are employed to learn the filter bank in the convolutional layers and the Leaky Rectified Linear Unit activation function is used in the final output layer to output the nonlinear features. Due to the advantage of LEPNet in recovering the geometric structure of the manifold in the low-dimension space, the features extracted by this network can facilitate characterizing the self-similarity better than the existing NLM methods. Experiments have been performed on the BrainWeb phantom and the real images. Experimental results demonstrate that among several compared denoising methods, the proposed method can provide more effective noise removal and better details preservation in terms of human vision and such objective indexes as peak signal-to-noise ratio (PSNR) and structural similarity index measure (SSIM).


Cytotoxic edema in neuro-Behcet's disease ?
We report a case of a 52-year-old woman with Behcet's disease who presented with dysarthria and right-sided hemiparesis. T2-weighted and diffusion-weighted images (DWI) showed a hyperintense lesion in the left pons with a relatively decreased apparent diffusion coefficient (ADC). Imaging showed almost complete resolution of the lesion after treatment with prednisolone. The atypical DWI and ADC findings in this case may reflect cytotoxic edema due to excitotoxic brain injury. This case thus illustrates the radiological diversity of neuro-Behcet's lesions.


Biotic Resistance to an Alien Amphibian: Larval Competition between Japanese Frogs and Invasive Cane Toads.
Understanding negative effects of native species on introduced taxa may suggest novel ways to control the invasive species by enhancing such effects. Previous studies have reported that the larvae of invasive cane toads (Rhinella marina) are suppressed by competition with the larvae of native anurans in Australia, but not in North America. We conducted laboratory trials to measure the effect of exposure to the larvae of Japanese frogs (Microhyla ornata, Fejervarya sakishimensis, Rhacophorus owstoni) on rates of survival, growth and development of cane toad tadpoles in Ishigaki Island, in southern Japan. Survival rates were not affected by native species, but competition with Dicroglossids and Rhacophorids (but not Microhylids) strongly reduced rates of growth and development in the tadpoles of cane toads. Dicroglossid tadpoles also reduced the body condition to toad tadpoles in addition to effects on SVL and mass. Encouraging populations of native frogs in toad-invaded areas of Japan thus may help to reduce the numbers of invasive cane toads.


The Cellular Underpinnings of the Human Cortical Connectome.
The functional properties of the human brain arise, in part, from the vast assortment of cell types that pattern the cortex. The cortical sheet can be broadly divided into distinct networks, which are further embedded into processing streams, or gradients, that extend from unimodal systems through higher-order association territories. Here, using transcriptional data from the Allen Human Brain Atlas, we demonstrate that imputed cell type distributions are spatially coupled to the functional organization of cortex, as estimated through fMRI. Cortical cellular profiles follow the macro-scale organization of the functional gradients as well as the associated large-scale networks. Distinct cellular fingerprints were evident across networks, and a classifier trained on post-mortem cell-type distributions was able to predict the functional network allegiance of cortical tissue samples. These data indicate that the in vivo organization of the cortical sheet is reflected in the spatial variability of its cellular composition.


Kinetics of internalization and degradation of asialo-glycoproteins in isolated rat hepatocytes.
The rate constants for internalization of surface-bound asialo-orosomucoid by hepatocytes were 0.040 min-1 at 20 degrees C, 0.18 min-1 at 30 degrees C and 0.28 min-1 at 40 degrees C. At 40 degrees C, internalization accounted for most of the increase in cell-associated radioactivity. The activation energy over the temperature range 20 to 40 degrees C was 68 +/- 7 (S.D.) kJ/mol. At 10 degrees C, most of the cell-associated asialo-orosomucoid was bound to the cell surface in a reaction which followed ordinary chemical kinetics. Pre-incubation of hepatocytes with a large concentration of unlabelled asialo-orosomucoid did not influence the uptake of subsequently added 125I-asialofetuin; neither was degradation of 125I-asialo-fetuin affected in this experiment. The fractional rate of degradation (the fraction of cell-associated asialo-fetuin which was degraded per unit time) was constant over a twelve-fold range of intracellular asialo-fetuin concentrations. Increasing the temperature from 20 to 30 degrees C produced approximately a ten-fold increase in the rate of degradation of either asialo-fetuin or asialo-orosomucoid. The average activation energies of degradation over the range 20 to 40 degrees C were 125 kJ/mol for asialo-fetuin and 149 kJ/mol for asialo-orosomucoid; however, the Arrhenius plots were not straight lines over this temperature range.


Genome Sequences of Salmonella enterica subsp. enterica Serovar Infantis Strains from Hungary Representing Two Peak Incidence Periods in Three Decades.
Four strains of Salmonella enterica subsp. enterica serovar Infantis isolated from humans (1980 to 1982) and broiler chickens (2016) have been sequenced. They represent the early and recent peak incidences of this serovar in Hungary. Genome sequences of these isolates provide comparative data on the evolution and rise of an endemic S Infantis clone in Hungary.


Periodic mesoporous organosilica as a multifunctional nanodevice for large-scale characterization of membrane proteins.
A versatile protocol has been developed for large-scale characterization of hydrophobic membrane proteins based on the periodic mesoporous organosilica (PMO) acting as both an extractor for hydrophobic substrate capture and a nanoreactor for efficient in situ digestion. With introduction of organic groups in the pore frameworks and the presence of hydrophilic silanol groups on the surface, PMO can be well-dispersed into not only an organic solution to concentrate the dissolved membrane proteins but also an aqueous solution containing enzymes for sequential rapid proteolysis in the nanopores. The unique amphiphilic property of PMO ensures a facile switch in different solutions to realize the processes of substrate dissolution, enrichment, and digestion effectively. Furthermore, this novel PMO-assisted protocol has been successfully applied for identification of complex membrane proteins extracted from mouse liver as proof of general applicability.


Adaptive specialization in position encoding while learning to read.
The present experiments focused on how orthographic processing develops during reading acquisition. Specifically, a large, cross-sectional sample of children from grade 2 to grade 4 was exposed to pairs of words, pseudowords, digit strings, and pseudo-letter (Armenian) strings while their sensitivity to transpositions (T) and substitutions (S) of internal characters was investigated in a perceptual matching task. The results showed that the development of identity and position decoding diverged between the four stimulus categories. Most importantly, sensitivity improved with longer exposure to formal education and higher reading level to both S and T pairs for digit strings, but only to S pairs for words and pseudowords. The results were successfully reproduced in two small independent samples. We propose a general framework, the Adaptive Specialization Hypothesis, to accommodate the results. According to this hypothesis, the transposed-letter effect is not a hard-wired feature of the orthographic processing system but an adaptive response of the developing orthographic system to the constraints of lexical access in several orthographies.


Evaluation of multicenter one-electron integrals of noninteger u screened Coulomb type potentials and their derivatives over noninteger n Slater orbitals.
Multicenter integrals over noninteger n Slater type orbitals with integer and noninteger values of indices u of screened Coulomb type potentials, f(u)(eta,r)=r(u-1)e(-etar), and their first and second derivatives with respect to Cartesian coordinates of the nuclei of a molecule are described. Using complete orthonormal sets of Psi(alpha) exponential type orbitals and rotation transformation of two-center overlap integrals, these integrals are expressed through the noncentral potential functions depending on the molecular auxiliary functions A(k) and B(k). The series expansion formulas derived for molecular integrals of screened Coulomb potentials and their derivatives are especially useful for the computation of multicenter electronic attraction, electric field, and electric field gradient integrals. The convergence of series is tested for arbitrary values of parameters of potentials and orbitals.


MEDI0639: a novel therapeutic antibody targeting Dll4 modulates endothelial cell function and angiogenesis in vivo.
The Notch signaling pathway has been implicated in cell fate determination and differentiation in many tissues. Accumulating evidence points toward a pivotal role in blood vessel formation, and the importance of the Delta-like ligand (Dll) 4-Notch1 ligand-receptor interaction has been shown in both physiological and tumor angiogenesis. Disruption of this interaction leads to a reduction in tumor growth as a result of an increase in nonfunctional vasculature leading to poor perfusion of the tumor. MEDI0639 is an investigational human therapeutic antibody that targets Dll4 to inhibit the interaction between Dll4 and Notch1. The antibody cross-reacts to cynomolgus monkey but not mouse species orthologues. In vitro MEDI0639 inhibits the binding of Notch1 to Dll4, interacting via a novel epitope that has not been previously described. Binding to this epitope translates into MEDI0639 reversing Notch1-mediated suppression of human umbilical vein endothelial cell growth in vitro. MEDI0639 administration resulted in stimulation of tubule formation in a three-dimensional (3D) endothelial cell outgrowth assay, a phenotype driven by disruption of the Dll4-Notch signaling axis. In contrast, in a two-dimensional endothelial cell-fibroblast coculture model, MEDI0639 is a potent inhibitor of tubule formation. In vivo, MEDI0639 shows activity in a human endothelial cell angiogenesis assay promoting human vessel formation and reducing the number of vessels with smooth muscle actin-positive mural cells coverage. Collectively, the data show that MEDI0639 is a potent modulator of Dll4-Notch signaling pathway.


A critical comparison between an ultra-high-performance liquid chromatography triple quadrupole mass spectrometry (UHPLC-QqQ-MS) method and an enzyme assay for anti-cholinesterase pesticide residue detection in cereal matrices.
Analytical method development for the control of pesticide residues occurring in significant dietary foodstuffs is of utmost importance considering their potential impact on consumer health and food market sustainability. Depending on the purpose, either instrumental analysis, mainly chromatographic methods, or screening assays, mostly using biorecognition affinity, are commonly used, featuring different advantages and drawbacks. To practically compare these two different types of analytical strategies, we applied them for the detection of (i) 97 organophosphate (OP) and carbamate (CM) pesticide residues in wheat flour and (ii) carbofuran (a carbamate insecticide) in wheat, rye and maize flour samples. Regarding high-end analysis, an ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-QqQ-MS) method was developed and validated achieving low limits of quantification (LOQs, from 0.002 to 0.040 mg kg-1) and a short chromatographic run (12 min). In terms of bioanalytical methods, a fast (17 min) and cost-efficient (∼0.01€ per sample) acetylcholinesterase (AChE) microplate assay for carbofuran screening was utilized. Importantly, carbofuran was the strongest of the 11 OP and CM tested pesticides achieving a half maximal inhibitory concentration (IC50) of 0.021 μM whilst the assay detectability was at the parts per billion level in all three cereal matrices. Based on the attained results, a critical discussion is presented providing the analytical merits and bottlenecks for each case and a wider outlook related to the application of analytical methods in the food safety control analytical scheme.


Melanoma, Melanin, and Melanogenesis: The Yin and Yang Relationship.
Melanin pigment plays a critical role in the protection against the harmful effects of ultraviolet radiation and other environmental stressors. It is produced by the enzymatic transformation of L-tyrosine to dopaquinone and subsequent chemical and biochemical reactions resulting in the formation of various 5,6-dihydroxyindole-2-carboxylic acid (DHICA) and 5,6-dihydroxyindole (DHI) oligomers-main constituents of eumelanin, and benzothiazine and benzothiazole units of pheomelanin. The biosynthesis of melanin is regulated by sun exposure and by many hormonal factors at the tissue, cellular, and subcellular levels. While the presence of melanin protects against the development of skin cancers including cutaneous melanoma, its presence may be necessary for the malignant transformation of melanocytes. This shows a complex role of melanogenesis in melanoma development defined by chemical properties of melanin and the nature of generating pathways such as eu- and pheomelanogenesis. While eumelanin is believed to provide radioprotection and photoprotection by acting as an efficient antioxidant and sunscreen, pheomelanin, being less photostable, can generate mutagenic environment after exposure to the short-wavelength UVR. Melanogenesis by itself and its highly reactive intermediates show cytotoxic, genotoxic, and mutagenic activities, and it can stimulate glycolysis and hypoxia-inducible factor 1-alpha (HIF-1α) activation, which, combined with their immunosuppressive effects, can lead to melanoma progression and resistance to immunotherapy. On the other hand, melanogenesis-related proteins can be a target for immunotherapy. Interestingly, clinicopathological analyses on advanced melanomas have shown a negative correlation between tumor pigmentation and diseases outcome as defined by overall survival and disease-free time. This indicates a "Yin and Yang" role for melanin and active melanogenesis in melanoma development, progression, and therapy. Furthermore, based on the clinical, experimental data and diverse effects of melanogenesis, we propose that inhibition of melanogenesis in advanced melanotic melanoma represents a realistic adjuvant strategy to enhance immuno-, radio-, and chemotherapy.


[Reconstruction of the anterior cruciate ligament using the patellar tendon: its magnetic resonance evaluation].
MRI of the knee was performed in 30 patients who had been submitted to arthroscopically-guided reconstruction of the anterior cruciate ligament from patellar tendon. The autograft structure was investigated and MR results were correlated with clinical findings. Partial/total meniscectomy had been carried out in 21/30 cases. The patients were imaged at various postoperative intervals (3-24 months) by means of an 0.5-T magnet (GE MR Max Plus) in full knee extension and internal rotation. Sagittal and axial T1-weighted images (slice thickness: 3 mm) were combined with real-time reconstruction which better demonstrated the whole graft. T2-weighted coronal images (slice thickness: 5 mm) were also acquired. In each patient the following clinical variables were considered: anterior drawer sign, Lachman test, pivot shift, degree of leg extension, and finally functional recovery. The following MR variables were then considered: structure and alignment of bone tunnels, structure and signal intensity of the graft, degree of synovial inflammation, structure and signal intensity of the posterior cruciate ligament and finally structure of the menisci and/or meniscal residues. Symptoms-MR correlation suggests that the different outcome of surgical reconstruction may depend on the correct alignment of the tibial and femoral bone tunnels and on good meniscal condition. Bone tunnels must be located on the same plane, posterior and parallel to the slope of the intercondylar roof, since angulation causes the latter to impact the graft during knee extension, with inflammation and risk for rupture. As for menisci, tiny residues or total ablation overload tha graft, whose signal increases and whose synovia becomes inflamed. The latter pattern is always distinguished from that of the autograft, whose signal intensity seems not to change in time. In conclusion, MR proved an accurate and non-invasive technique to image this kind of postoperative knee, since metallic artifacts do not reach the joint space.


Inelastic neutron scattering study of light-induced dynamics of a photosynthetic membrane system.
Inelastic neutron scattering was employed to study photoeffects on the molecular dynamics of membranes of the photosynthetic bacterium Rhodopseudomonas viridis. The main photoactive parts of this biomolecular system are the chlorophyll molecules whose dynamics were found to be affected under illumination by visible light in a twofold manner. First, vibrational modes are excited at energies of 12(2) and 88(21) cm(-1). Second, a partial "freezing" of rotational modes is observed at energies of 1.2(3) and 2.9(5) cm(-1). These results are attributed to a possible coupling between molecular motions and particular mechanisms in the photosynthetic process.


Wound-inducible and organ-specific expression of ORF13 from Agrobacterium rhizogenes 8196 T-DNA in transgenic tobacco plants.
Tissue-specific expression of the ORF13 promoter from Agrobacterium rhizogenes 8196 was assessed throughout the development of transgenic tobacco plants using a GUS reporter gene. ORF13 exhibited high activity in roots but with different patterns of expression. The activity of the ORF13 promoter in vascular tissues increased from the base to the tip of the stem. The ORF13 promoter is wound inducible in a limited area adjacent to the wound site. The time course of wound induction of ORF13 in transgenic tobacco containing an ORF13 promoter-GUS translational fusion was similar to that previously described for genes involved in plant defense responses. A series of 5' deletions of the ORF13 promoter fused to the beta-glucuronidase gene was examined for expression in roots and leaves of transgenic plants. Cis-acting elements that modulate quantitative expression of the transgene after wounding were detected.


Class II Division 1 in New Dimension: Role of Posterior Transverse Interarch Discrepancy in Class II Division 1 Malocclusion During the Mixed Dentition Period.
Posterior transverse discrepancy as seen in some cases of Class II Division 1 malocclusion in mixed dentition period can be related to typical skeletofacial characteristics. These features when studied early in the mixed dentition period give a clear view of the desired appropriate treatment plan in a particular case. The purpose of this study was to establish a simple method to determine the posterior (intermolar) transverse discrepancy and craniofacial skeletal features between the dental arches during the mixed dentition in a sample of Class II Division 1 patients to provide diagnostic and therapeutic guidance in the early approach. A sample of 60 Class II Division 1 patients in mixed dention that were divided into 30 Class II Division 1 patients with posterior transverse interarch discrepancy {Class II (I) PTID group} and 30 Class II Division 1 patients without posterior transverse interarch discrepancy {Class II (I) NPTID group}. Thirty Class I subjects in mixed dentition were included as control. The skeletal features of the Class II group without PTID are those of the skeletal Class II associated with 'anatomic' mandibular retrusion (due to a micrognathic mandible) and those of the Class II group with PTID as skeletal Class II associated with only a 'functional' mandibular retrusion (due to a posteriorly displaced mandible of normal size). This study confirmed the role of occlusion in the control of maxillomandibular skeletal relationships.The treatment strategies could be planned on the basis of the transverse component of Class II Division 1 groups in the mixed dentition period.


What do patients and their carers want to know about stroke? A two-year follow-up study.
To clarify what issues are important to stroke patients and their carers. To determine whether these issues change over time. Prospective study of consecutive patients admitted to hospital with a diagnosis of an acute stroke. Each participant had interviews at six and 24 months. In addition, a subgroup of these patients (consecutive discharges over a two-month period) were also seen at two weeks post discharge. Hospital-based cohort of stroke survivors. Interviewed in their own homes. Documentation of the questions asked. At two weeks, six and 24 months, a median of three, two and three questions were asked by each patient respectively. Enquiries about basic aspects of stroke were common but diminished over time. Fear of recurrence was apparent at all three interview periods. Enquiries about the psychological sequelae of stroke became more prevalent at six and 24 months. At two years, 32% of respondents asked about concentration/memory difficulties with smaller numbers commenting on tiredness, depression and frustration. At two years, 18% of the sample were still uncertain of their chances of further recovery. Patients with stroke continue to have unanswered questions even two years after their stroke. The types of questions asked changed over time.


The unilateral occipital transtentorial approach for pineal region meningiomas: a report of 15 cases.
In the current study, we reviewed and re-evaluated the experiences of microsurgical management for pineal region meningiomas via the unilateral occipital transtentorial approach (Poppen's approach). Clinical data were obtained on 15 meningiomas of the pineal region, which underwent microsurgery via unilateral Poppen's approach from March 2009 to June 2012. These patients were hospitalized in our department; their data were collected and analyzed retrospectively. The tumors were removed via the right Poppen's approach in 12 cases and left Poppen's approach in 3 cases, and intraoperative external ventricular drainage was performed for hydrocephalus in 3 cases. As a result, gross total resection was achieved in 11 cases, near total resection in 3 cases and subtotal resection in 1 case. All resected tumors were pathologically confirmed. The postoperative complications included two cases of homonymous hemianopia, and deteriorated Parinaud syndrome and diplopia in one case. Ten cases were followed up (range 1-4 years) and no death occurred. On the basis of the existing literature and our experiences, the unilateral Poppen's approach is appropriate for most meningiomas of the pineal region that are small or intermediate in size. However, gross total resection might be difficult via the unilateral Poppen's approach for large-sized meningiomas with much contralateral infratentorial extension due to limited exposure. For these cases, combined supra-infratentorial or bilateral Poppen's approaches are recommended. Preoperative or intraoperative external ventricular drainage can increase tumor exposure and improve microsurgical effects.


[Effects of Tetrandrine Prenatal Intervention on Alveolar Epithelial Cells Type I Differentiation in Rat Model of Nitrofen-induced Congenital Diaphragmatic Hernia].
To investigate the effects of Tetrandrine (TET) prenatal intervention on the differentiation of alveolar epithelial cells type I (AEC I) in rat model of Nitrofen-induced congenital diaphragmatic hernia (CDH). Timed-pregnant Sprague-Dawley rats were divided into three groups, namely control, CDH and TET group on day 9.5 of gestation. The rats in TET group and CDH group were given 125 mg of Nitrofen by gavage one time, while the rats in control group were given the same dose of seed fat. After that, the rats in TET group was given 30 mg/kg of TET by gavage once a day for three days from day 18.5 of gestation, while the rats in CDH and control group were given the same dose of normal saline. On day 21.5 of gestation, all fetuses were delivered by cesarean, the lungs of fetuses were histologically evaluated by microscope and electron microscope. The expressions of type I cell-specific protein (RT140) and thyroid transcription factor 1 (TTF1) in alveolar fluid content were analyzed by RT-PCR and immunohistochemistry staining. To detect the number of AEC I and AEC II of each group by transmission electron microscopy and calculate the percentage of AEC I and AEC II (I/II%). The microscope and electron microscope study found the lungs of fetuses in CDH group showed marked hypoplasia, in contrast to the improvement of hypoplasia in TET fetuses. The pulmonary alveolar area had significant difference statistically (P < 0.01) in each group, which present as control > TET > CDH. I/II% had significant difference statistically (P < 0.01) in each group, which present as control > TET > CDH. The expression level of TTF1 was up-regulated in both CDH and TET groups, and it was higher in CDH group (P < 0.01). The expression level of RT140 were down-regulated in CDH and TET groups, which was lower in CDH group (P < 0.01). The development of AEC I was interfered in CDH rat model, TET prenatal treatment could improve the lung development of CDH.


Physical and histopathological assessment of the effects of metallic stents on radiation therapy.
To evaluate whether simultaneous metallic stent (MS) placement and radiotherapy are feasible, phantom and animal experiments were performed. The interface dose by external irradiation (EI) or intracavity irradiation (II) to 5 kinds of MS was measured using the charge-coupled device (CCD) camera with a thermoluminescent (TL) sheet, and backscatter and absorption were evaluated using composite method. Lineac 10 MV X-ray irradiated the MS in close contact with the TL sheet. II was performed using (192)Ir, and the irradiation dose transmitted through the MS was measured using the TL sheet. The ratio of the CCD value of the MS wire region to that of the MS non-wire region was defined as the dose perturbation factor (DPF). Furthermore, the effects of a combination of (60)Co gamma-ray EI and MS placement in the normal common bile duct were histopathologically evaluated in dogs. In the phantom experiments of EI, in backscatter by the MS, the DPF was 1.09 for CZ, and 1.03 for Pal, but no backscatter was detected in the remaining 3 MS. In absorption by the MS, the DPF was 0.92, 0.97, 0.97, and 0.98 for CZ, Wall, Pal, and Vel, respectively, but no absorption was detected in U. Flex. In those of II, the DPF of absorption was 0.91, 0.98, and 0.98 for CZ, U. Flex, and Wall, respectively, but no absorption was detected in Pal and Vel. The animal experiments showed infiltration of inflammatory cells and fibrosis in the case of both MS placement and EI. These changes were marked in EI treating after MS placement, but neither severe ulcer nor perforation was found. In conclusion, these results suggested that the effect of MS should be considered carefully when simultaneous MS placement and EI is performed clinically.


Women's retirement and self-assessed well-being: an analysis of three measures of well-being among recent and long-term retirees relative to homemakers.
Focusing on women from the U.S. over 60 years old in 2006, this study analyzed the relationship between retirement and three subjective measures of well-being: depressive symptoms, financial worries, and health. Drawing on the life course perspective and the heterogeneity of women's labor force experiences, this study contrasted the well-being of recent retirees with those who self-identified as homemakers (n = 1695) and long-term retirees with homemakers (n = 2012). Findings indicated that being a recent retiree was associated with more favorable reports of health and that being a long-term retiree was more favorably associated with accounts of all three outcome measures relative to homemakers. Thus, despite the major role change they experienced, findings support the notion that participating in the paid labor force may have been a protective factor with regard to self-assessed well-being.