Prolonging Reproductive Life after Cancer: The Need for Fertoprotective Therapies.
The survival rate of reproductive-age patients with cancer is increasing, reflecting the advent of better and more efficient therapies. Cancer survivors seek the resumption of a normal and healthy life, which often includes starting a family. Unfortunately, many cancer treatments increase the risk of premature ovarian insufficiency (POI) and infertility. Assisted reproductive technologies (ART) can address infertility, but fail to preserve the natural function of the ovaries as a source of hormones that regulate many aspects of women's health. The advancement of fertoprotective technologies is hindered by our lack of understanding of oocyte biology and their sensitivity to cancer therapies. Because many cancer treatments cause DNA damage, apoptosis is thought to be the major mechanism eliminating damaged oocytes. Indeed, recent studies in mice demonstrate that targeting proteins involved in apoptosis protects oocytes and prevents infertility in females exposed to radiation. Therefore, a better appreciation of oocyte response to radiation and anticancer drugs will uncover new targets for the development of specialized therapies to prevent ovarian failure. We make a case here for the necessity of such fertoprotective treatments. We review recent findings that have significantly advanced our understanding of how cancer therapies induce apoptotic death in oocytes, and how we could use this knowledge to design better fertoprotective treatments.


Relationship between hypertension and smoking: A preliminary study in South Kashmiri population of J&K.
Smoking has been found to have a profound effect on mortality and cause-specific cardiovascular events in hypertension with significant interactions between the effects of smoking and hypertension and diabetes. Nevertheless, smoking is a major modifiable risk factor for cardiovascular disease (CVD). The present study was conducted on the patients visiting the medical Out Patient Department, Government Medical College (OPD GMC), Anantnag, for consultation with an aim to find whether smoking can be linked with CVD as a cause. A total of 304 patients were observed during this period for health check-ups. The result reveals that 90% of male subjects across the age groups formulated in this study were in habit of smoking. In addition, 75% of female subjects across all age groups were also found to be in the habit of smoking. The majority of subjects including male subjects were potentially susceptible to CVD. The present prospective study was carried out to assess the role of smoking in causing hypertension and thereby various CVDs among the south Kashmiri population with high blood pressure levels in presence of high smoking rates. Smoking acutely exerts a hypertensive effect, mainly through the stimulation of the sympathetic nervous system. Chronic smoking affecting arterial stiffness and wave reflection has greater detrimental effect on central blood pressure, which is more closely related to target organ damage than brachial blood pressure. Hypertensive smokers are more likely to develop severe forms of hypertension, including malignant and renovascular hypertension, an effect likely due to accelerated atherosclerosis. Smoking is potentially a leading cause of CVD among the South Kashmiri Population with high blood pressure levels in presence of high-smoking rates. Therefore, imperative measures regarding cessation of smoking are essential to prevent CVD which in line with clinical practice guidelines and policies should be emphasized to treat nicotine addiction in smokers by incorporating multicomponent and multilevel approaches for the better management of BP among the population studied.


Cellular localization of BARF1 oncoprotein and its cell stimulating activity in human epithelial cell.
BARF1 gene encoded by Epstein-Barr virus is capable of immortalizing the primary monkey epithelial cells and of inducing malignant transformation in human EBV-negative B cell lines as well as rodent fibroblast. This oncoprotein is a secreted protein capable of acting as a powerful mitogen. We have studied the effect of BARF1 protein in transfected or BARF1 protein treated human HaCaT epithelial cells. In BARF1-transfected cells, cell growth was activated and its protein was found both in culture medium and cellular compartment (membrane, cytoplasm and nuclei). When purified BARF1 protein was exogenously added in the cell culture medium of HaCaT cells in absence of fetal calf serum led to its entrance into cells and its intracellular localization in cytoplasm, nuclear periphery and nuclei at 14h treatment, determined by confocal and immunoelectron microscopy. Cell fractionation confirmed its nuclear localization. Nuclear localization was observed in both systems. More interestingly, purified BARF1 protein p29 exogenously added in the cell culture medium activated cell passage of G1 to S phase. S phase activation by its autocrine activity and its tumorigenic activity would be associated with the development of EBV-associated carcinomas.


Identification of clinical markers of specific language impairment in adults.
To investigate the usefulness of 3 tasks known to be effective diagnostic clinical markers of specific language impairment (SLI) in children: (a) nonword repetition, (b) sentence repetition, and (c) grammaticality judgments of finiteness marking. Two groups of young adults, 13 with SLI and 18 with typical language, completed 3 experimental tasks: (a) nonword repetition, (b) sentence repetition, and (c) grammaticality judgments of sentences that were either correct or contained an omitted finiteness marker, an overt agreement error, or an omitted progressive -ing. Analyses included receiver operating characteristic curve analyses and computation of likelihood ratios associated with the use of each task as a clinical marker for SLI, as well as development of a logistic regression model that used multiple tasks as predictors. Each marker task significantly contributed to classification of adults as affected or unaffected by SLI, with moderate positive and negative likelihood ratios. A combination of the 3 marker tasks was the best predictor of affectedness status with moderate to large likelihood ratios. The results suggest that SLI persists into adulthood and that effective clinical markers of this disorder are similar to those used to identify SLI in children. Refinement of these tasks to increase their likelihood ratios will improve their usefulness in diagnosing SLI in adults.


Pre- and post-saccadic stimulus timing in saccadic suppression of displacement - A computational model.
When the target of a saccadic eye movement is displaced while the eyes move this displacement is often not noticed (saccadic suppression of displacement, SSD). We present a neurobiologically motivated, computational model of SSD and compare its simulation results to experimental data. The model offers a simple explanation of the effects of pre- and post-saccadic stimulus blanking on SSD in terms of peri-saccadic network dynamics. Under normal peri-saccadic conditions pre-and post-saccadic stimulus traces are recurrently integrated with reference to present and future eye position, whereas blanking diminishes the pre-saccadic stimulus trace and thus leads to an uninfluenced integration of the post-saccadic stimulus trace. We show that part of the intersubject variability in SSD can be explained by differences in decision thresholds of this integration process.


[The medical treatment of cryptorchism in early childhood].
To evaluate the efficacy of early treatment of cryptorchidism, we studied 154 children, 133 with unilateral and 21 bilateral cryptorchidism, between the ages of 6 months and 6 years. Only fullterm newborns without other pathological signs were selected for treatment which was undertaken only after the sixth month of life, when the time of late spontaneous testicular descent has been passed. By clinical evaluation, cryptorchid testes were classified as not palpable, inguinal and prescrotal. Patients were treated by LHRH nasal spray 200 mcg in each nostril 3 times a day (total 1.2 mg/day) for 4 weeks. In the case of failure, HCG (500 I.U. im. 3 times a week for 3 weeks) was further administered. We considered as therapeutic success testicular descent into the lower half of the scrotum. By LHRH treatment 36 testes (20.5%) reached the scrotum, when HCG was added in unsuccessful cases 47 other gonads (26.8%) descended. Total descent rate by LHRH + HCG was 47.3% (table 1). Uni- and bilateral forms of cryptorchidism responded to therapy without any significant difference (table 2). Abdominal testes failed to descend into the scrotum, 28.7% of inguinal testes and 81.3% prescrotal testes descended. Scrotal descent was dependent only by position of cryptorchid testes and not by age of patients (table 3). Higher descent rates obtained at older ages were due to higher incidence of milder forms of cryptorchidism (table 3). Side effects of combined therapy were light. In our experience, medical treatment by LHRH + HCG started after the first 6 months of life causes testicular descent in about one half of testes; it can place into the scrotum gonads with better fertility prognosis.


Epidemiology and prevalence of Toxoplasma gondii infection in the Iberian hare (Lepus granatensis).
Hares are important game species in Europe and their meat is consumed by humans. Toxoplasmosis is an important cause of mortality in hares in Nordic countries but little is known of Toxoplasma gondii infection in the Iberian hare (Lepus granatensis). Sera from 298 Iberian hares from Navarra (North Spain) were assayed for antibodies against T. gondii by the modified agglutination test. The samples were collected at necropsy during three consecutive years (2009-2011). Titers of 1:25 and higher were found in 34 hares (11.4%; CI95%: 7.8-14.9). Significant differences in seroprevalence were observed among geographical areas, years of sampling and age groups. The highest seroprevalence and the highest titers were observed in 2009, indicating fluctuating rates of transmission. Significantly higher seroprevalence was observed in the juvenile age group compared to the adult hare group. More than 40% of juvenile hares were seropositive the first year of study, seroprevalence drastically decreased in the juvenile animals sampled in the second year and was negligible in those sampled in the third year in this group. No clinical cases were detected in the study area and T. gondii was not detected by PCR in the liver of the 34 seropositive hares tested. These data may indicate that most juvenile seropositive hares did not survive as adults in the consecutive year or that there is a short-term humoral immune response against T. gondii in Iberian hares.


Agrobacterium rhizogenes T-DNA genes capable of inducing hairy root phenotype.
Segments of the TL-DNA of the agropine type Ri plasmid pRi 1855 encompassing single and groups of open-reading frames were cloned in the Ti plasmid-derived binary vector system Bin 19. Leaf disc infections on Nicotiana tabacum led to transformed plants, some of which showed typical hairy root phenotypes, such as the wrinkled leaf morphology, excessive and partially non geotropic root systems and the ability of leaf explants to differentiate roots in a hormone-free culture medium. Particularly interestingly, most of these traits were shown by plants transformed with a TL-DNA segment encompassing the single ORF 11, corresponding to the rolB locus. Hairy root can be induced by this latter T-DNA segment on wounded stems of tobacco plants; hairy root induction on carrot discs requires, on the contrary, a more complex complement of TL-DNA genes.


Relationships between arousal-related moods and episodic tension-type headache: a biopsychological study.
An exploratory study was conducted examining arousal-related moods and episodic tension-type headache. Twelve subjects meeting International Headache Society criteria for episodic tension-type headache and 12 headache-free controls recorded headache activity and mood eight times daily for 14 consecutive days. Moods were measured using the Activation-Deactivation Adjective Check List, a self-report list that subjectively represents general arousal along two dimensions of Tension and Energy. Headache subjects had higher Tension levels than controls even in the absence of pain, and greater variation in this dimension as well. Within the headache group, Tension during pain-free periods was significantly lower than when experiencing headache, and was correlated with headache activity. The results were taken to support Thayer's (1989) biopsychological model of mood and arousal, and are discussed in terms of the model's heuristic value for general arousal and headache research.


Cerebral astrocytes transport ascorbic acid and dehydroascorbic acid through distinct mechanisms regulated by cyclic AMP.
Cerebral ischemia and trauma lead to rapid increases in cerebral concentrations of cyclic AMP and dehydroascorbic acid (DHAA; oxidized vitamin C), depletion of intracellular ascorbic acid (AA; reduced vitamin C), and formation of reactive astrocytes. We investigated astrocytic transport of AA and DHAA and the effects of cyclic AMP on these transport systems. Primary cultures of astrocytes accumulated millimolar concentrations of intracellular AA when incubated in medium containing either AA or DHAA. AA uptake was Na+-dependent and inhibited by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), whereas DHAA uptake was Na+-independent and DIDS-insensitive. DHAA uptake was inhibited by cytochalasin B, D-glucose, and glucose analogues specific for facilitative hexose transporters. Once inside the cells, DHAA was reduced to AA. DHAA reduction greatly decreased astrocytic glutathione concentration. However, experiments with astrocytes that had been previously depleted of glutathione showed that DHAA reduction does not require physiological concentrations of glutathione. Astrocyte cultures were treated with a permeant analogue of cyclic AMP or forskolin, an activator of adenylyl cyclase, to induce cellular differentiation and thus provide in vitro models of reactive astrocytes. Cyclic AMP stimulated uptake of AA, DHAA, and 2-deoxyglucose. The effects of cyclic AMP required at least 12 h and were inhibited by cycloheximide, consistent with a requirement for de novo protein synthesis. Uptake and reduction of DHAA by astrocytes may be a recycling pathway that contributes to brain AA homeostasis. These results also indicate a role for cyclic AMP in accelerating the clearance and detoxification of DHAA in the brain.


Improvements in immunization compliance using a computerized tracking system for inner city clinics.
Vaccination compliance rates were calculated for 1995 to 2001 for enrolled patients, based on the Centers for Disease Control and Prevention guidelines and age-appropriate vaccine schedules. The results reported here indicate computerized tracking with the Doctor's Pediatric Immunization Program (Dr. PIP) maintained vaccine compliance rates (> 90%) in healthy and immunocompromised children at 2 months and 12 months of age. Instituting the computerized system has yielded nearly optimal results in both indigenous inner-city clinics. Despite the efficient progress made by automated tracking, the results for specific vaccine strategies (Varicella) and target groups (human immunodeficiency virus, high-risk indigent populations) may require on-going and intensive educational efforts to achieve optimization levels.


Overexpression of human DNA topoisomerase I in insect cells using a baculovirus vector.
The 3645-bp human DNA topoisomerase I cDNA isolated by D'Arpa et al. (Proc. Natl. Acad. Sci. USA 85, 1988, 2543-2547) was integrated into the Autographa californica multiple nuclear polyhedrosis virus genome. The recombinant protein was expressed by infecting the SF9 insect cell line with this baculovirus and resulted in a 100-fold overexpression of human DNA topoisomerase I compared to the level found in human cell lines. This 100-kDa recombinant protein has the same electrophoretic mobility as the human DNA topoisomerase I from HeLa cells and is recognized by topoisomerase I-specific monoclonal antibody. The recombinant DNA topoisomerase I was isolated and purified to homogeneity with a two-step fractionation protocol and has a specific activity of 2 x 10(6) U/mg. Enzymatic properties such as stimulation by magnesium and inhibition by camptothecin resemble properties of the enzyme purified from human cell lines.


Effect of the Ratio of Magnetite Particle Size to Microwave Penetration Depth on Reduction Reaction Behaviour by H2.
In this study, we investigated reduction of magnetite by H2 during microwave irradiation. This process combines the advantages of microwave irradiation and using H2 as a reducing agent to mitigate CO2 emissions during the ironmaking process. Weight change measurements showed that a reduction of 75% was achieved after treatment under H2 for 60 min. For better understanding of the effective parameters in microwave chemistry, scanning electron microscopy, combined with energy-dispersive X-ray spectroscopy (SEM-EDX), was performed, which demonstrated a greater reduction of large particles (>40 μm) than small particles. This behaviour could be attributed to the higher microwave absorption capability of large particles with a higher ratio of particle size to penetration depth (d/δ). Small particles behave as transparent material and are heated via conduction and/or convection; thus, there is no contribution from the catalytic effect of microwaves to the reduction reaction. Moreover, the reduction of Fe3O4 to Fe0.94O, followed by transformation to Fe, seems to proceed from the surface toward the centre of the particle despite the volumetric microwave heating. This could be due to the higher gas accessibility of iron oxide on the particle surface than in the particle centre.


[Treatment of Mediastinitis after Open Heart Surgery Using Negative Pressure Wound Therapy with Irrigation].
Mediastinitis occurs after open heart surgery in a small number of cases. When it occurs, early diagnosis and treatment are important. A 69-year-old male patient suffered from mediastinitis after total aortic arch replacement. He has cured completely by negative pressure wound therapy (NPWT) with irrigation method. The vacuum-assisted closure( VAC) method is very useful for wound repair and has recently been used to treat mediastinitis. However, the use of VAC alone does not always result in complete cure. NPWT with irrigation is a very useful infection control method. Performing NPWT before VAC might contribute to improving the outcomes of mediastinitis treatment. However, it is difficult to decide when to switch from NPWT with irrigation to VAC.


Seasonal shedding of Escherichia coli O157:H7 in ruminants: a new hypothesis.
Seasonal shedding of Escherichia coli O157:H7 in ruminants is well documented; however, viable explanations for this phenomenon are lacking. The fecal prevalence of E. coli O157:H7 in ruminants is the highest in the summer months, decreasing to low or undetectable levels in the winter. To determine if day length is correlated to seasonal shedding, nine reports of E. coli O157:H7 prevalence in cattle were selected for similarity of sampling technique, culture methodology, cattle type, and ability to determine approximate sampling month and location, representing three regions in North America (southern Canada, midwestern United States, and the southern United States/Mexico). Correlation and regression analysis revealed a positive correlation existed between day length (r = 0.67; R2 = 0.45; P = 0.0009) and, to a lesser extent, ambient temperature (r = 0.43; R2 = 0.19; P = 0.05) and E. coli O157:H7 prevalence. Based on these results, a study was conducted in a commercial feedlot to examine the effect of artificial lighting on E. coli O157 prevalence. Four pens of cattle received approximately 5 hours of artificial lighting daily (in addition to the natural light) for 60 days and four pens served as controls. Freshly voided fecal samples (representing approximately 30% of the steers/pen) were collected from the pen floor and cultured for E. coli O157 after 25 and 53 days of artificial lighting and 28 and 43 days following cessation of the lighting treatment. Fecal prevalence of E. coli O157 remained constant in the lighted pens whereas prevalence was lower (P < 0.01) in the control treatment after 53 days of lighting. Forty-three days following cessation of the lighting treatment, prevalence decreased in the lighted treatment group to levels comparable (P > 0.20) to control levels. Understanding the mechanisms underlying the seasonality of this important foodborne pathogen will enable the implementation of effective control strategies when it is most prevalent.


Ontogenic differences in the inhibition of gastric acid secretion by epidermal growth factor.
Gastric secretions were studied in rats by pyloric ligation in vivo. The effects of epidermal growth factor (EGF) administered s.c. on gastric secretion were evaluated at different stages of development (8, 14, 20 and 30 postnatal days). The rates of fluid, protein and acid outputs were very low in developing rats but increased in maturing rats. The rate of acid output in 8- day-old rats (3.83 +/- 1.16) was not different from that in 14-day-old rats (4.84 +/- 0.99), whereas the rate of acid output in 20-day-old rats was 11-fold greater than that in 14-day-old rats, and it was 21-fold greater in 30-day-old rats. Subcutaneous administration of 30 micrograms/kg b.wt. of EGF significantly suppressed the gastric secretion of fluid, protein and acid in 20- and 30-day-old rats. In 30-day-old rats, acid output was 85% lower at 1 hr after EGF administration and in 20-day-old rats it was 85% lower at 2 hr and 50% lower at 3 hr. Interestingly, EGF had no effect on basal gastric secretions in 8- and 14-day-old rats; EGF also had no effect on the gastric acid output that was stimulated by pentagastrin administration in 14-day-old rats. In 20-day-old rats, inhibitory effects of EGF lasted for 3 hr before gastric secretions rebounded to normal levels, but inhibition lasted for only 1 hr in 30-day-old rats.(ABSTRACT TRUNCATED AT 250 WORDS)


Intra- and intersexual selection on male body size in the annual killifish Austrolebias charrua.
Since many traits are involved in both female mating decisions and male contest outcomes, female mate choice and male competition can act in concert to intensify sexual selection on male traits, or in opposition to weaken it. In the sexually dimorphic annual killifish, Austrolebias charrua, we evaluated the effect of male body size on female mate choice, male-male competition, and their interaction. We carried out an experiment with three consecutive stages: (i) female choice test between males of different size in a classic two-choice device, (ii) agonistic interactions between males used in the previous stage, and (iii) a second female choice test to evaluate preference consistency in females that either were allowed or were prevented from observing the male competition. Larger males were preferred by females and became socially dominant in agonistic interactions. Further, females were consistent in their choices, and this consistency was independent of whether they had observed or not the male contest. Our research shows that, in A. charrua, intrasexual competition and female mate choice act in concert with respect to male body size. The unique life-history of Austrolebias and the high repeatability of mate-choice assays make this system a promising candidate for studies of behavioural evolution.


Prostate-specific antigen testing in men aged 40-64 years: impact of publication of clinical trials.
We assessed the impact of the publication of trials and changes in recommendations on the rates of prostate-specific antigen (PSA) screening in men aged 40 to 64 years by analyzing monthly medical claims for PSA testing in a commercial insurance database from 2001 to 2011, covering more than 1.5 million men in each year. The testing rates for men aged 40 to 49 years, 50 to 59 years, and 60 to 64 years were 12.1%, 32.7%, and 42.7%, respectively, in 2001 vs 15.7%, 34.2%, and 42.0%, respectively, in 2011. Men aged 40 to 49 years experienced a gradual increase in testing rate from 2001 through 2008 (annual change in PSA testing per 10,000 men [AC] = 4.37; P < .001), which became flat from mid-2009 through 2011(AC = -0.06; P =.98). The slope of PSA testing rates did not change in men aged 50 to 59 years or 60 to 64 years with the publication of the results of the large trials in 2009 or with the subsequent changes in recommendations on PSA testing.


Migration and division in cell monolayers on substrates with topological defects.
Collective movement and organization of cell monolayers are important for wound healing and tissue development. Recent experiments highlighted the importance of liquid crystal order within these layers, suggesting that +1 topological defects have a role in organizing tissue morphogenesis. We study fibroblast organization, motion, and proliferation on a substrate with micron-sized ridges that induce +1 and -1 topological defects using simulation and experiment. We model cells as self-propelled deformable ellipses that interact via a Gay-Berne potential. Unlike earlier work on other cell types, we see that density variation near defects is not explained by collective migration. We propose instead that fibroblasts have different division rates depending on their area and aspect ratio. This model captures key features of our previous experiments: the alignment quality worsens at high cell density and, at the center of the +1 defects, cells can adopt either highly anisotropic or primarily isotropic morphologies. Experiments performed with different ridge heights confirm a prediction of this model: Suppressing migration across ridges promotes higher cell density at the +1 defect. Our work enables a mechanism for tissue patterning using topological defects without relying on cell migration.


High Salt Intake Attenuates Breast Cancer Metastasis to Lung.
Diet-related factors are thought to modify the risk of cancers, while the influence of high salt intake remains largely uncharacterized. Breast cancer is the most common cancer in women worldwide. In the present study, we examined the effect of salt intake on breast cancer by using a 4T1 mouse mammary tumor model. Unexpectedly, both the fitness and the survival rate of the tumor-bearing mice were improved by high salt intake. Similarly, high salt intake suppressed the primary tumor growth as well as metastasis to lung in mice. Mechanistically, high salt intake greatly reduced food intake and thus might exert antitumor effect through mimicking calorie restriction. Immunoblotting showed the lower proliferation marker Ki-67 and the higher expression of the tumor suppressor gene p53 in tumors of high salt intake mice. Importantly, high salt intake might induce hyperosmotic stress, which sensitized breast cancer cells to p53-dependent anoikis. Collectively, our findings raise the possibility that endogenous salt deposition might act as the first-line defense system against breast cancer progression as well as metastasis.


Intravitreal delivery of AAV-NDI1 provides functional benefit in a murine model of Leber hereditary optic neuropathy.
Leber hereditary optic neuropathy (LHON) is a mitochondrially inherited form of visual dysfunction caused by mutations in several genes encoding subunits of the mitochondrial respiratory NADH-ubiquinone oxidoreductase complex (complex I). Development of gene therapies for LHON has been impeded by genetic heterogeneity and the need to deliver therapies to the mitochondria of retinal ganglion cells (RGCs), the cells primarily affected in LHON. The therapy under development entails intraocular injection of a nuclear yeast gene NADH-quinone oxidoreductase (NDI1) that encodes a single subunit complex I equivalent and as such is mutation independent. NDI1 is imported into mitochondria due to an endogenous mitochondrial localisation signal. Intravitreal injection represents a clinically relevant route of delivery to RGCs not previously used for NDI1. In this study, recombinant adenoassociated virus (AAV) serotype 2 expressing NDI1 (AAV-NDI1) was shown to protect RGCs in a rotenone-induced murine model of LHON. AAV-NDI1 significantly reduced RGC death by 1.5-fold and optic nerve atrophy by 1.4-fold. This led to a significant preservation of retinal function as assessed by manganese enhanced magnetic resonance imaging and optokinetic responses. Intraocular injection of AAV-NDI1 overcomes many barriers previously associated with developing therapies for LHON and holds great therapeutic promise for a mitochondrial disorder for which there are no effective therapies.


Jet length/velocity ratio: a new index for echocardiographic evaluation of chronic aortic regurgitation.
Management of aortic regurgitation depends on the assessment for severity. Echocardiography remains as the most widely available tool for evaluation of aortic regurgitation. In this manuscript, we describe a novel parameter, jet length/velocity ratio, for the diagnosis of severe aortic regurgitation. A total of 30 patients with aortic regurgitation were included to this study. Severity of aortic regurgitation was assessed with an aortic regurgitation index incorporating five echocardiographic parameters. Jet length/velocity ratio is calculated as the ratio of maximum jet penetrance to mean velocity of regurgitant flow. Jet length/velocity ratio was significantly higher in patients with severe aortic regurgitation (2.03 ± 0.53) compared to patients with less than severe aortic regurgitation (1.24 ± 0.32, P < 0.001). Correlation of jet length/velocity ratio with aortic regurgitation index was very good (r(2) = 0.86) and correlation coefficient was higher for jet length/velocity ratio compared to vena contracta, jet width/LVOT ratio and pressure half time. For a cutoff value of 1.61, jet length/velocity ratio had a sensitivity of 92% and specificity of 88%, with an AUC value of 0.955. Jet length/velocity ratio is a novel parameter that can be used to assess severity of chronic aortic regurgitation. Main limitation for usage of this novel parameter is jet impringement to left ventricular wall.


Teaching Strategies and Psychological Effects of Entrepreneurship Education for College Students Majoring in Social Security Law Based on Deep Learning and Artificial Intelligence.
This study aims to achieve the goal of cultivating and reserving emerging professional talents in social security law, improve the curriculum and mechanism of entrepreneurship education, and improve students' entrepreneurial willingness and entrepreneurial ability. Deep learning technology is used to study the psychological effects of entrepreneurship education for college students majoring in social security law. Firstly, the concept of entrepreneurial psychology is elaborated and summarized. A related model is designed using the theory of proactive personality and planned behavior through questionnaire survey and regression analysis to explore the relationship between students' entrepreneurial psychology and entrepreneurial intention. Secondly, an entrepreneurship education method based on deep learning is proposed, and a teaching model of multi-dimensional collaborative entrepreneurship education practice is constructed. On this basis, the deep learning algorithm combines the characteristics of the personalized recommendation algorithm to construct an efficient Problem-Based Learning (PBL) learning resource recommendation algorithm. Finally, the proposed method is tested. The results show that the Significant (Sig.) value of students who have participated in PBL deep learning courses is less than 0.05, indicating that PBL significantly improves students' learning ability and the ability to deal with entrepreneurial environments. The results verify the impact of entrepreneurial learning on entrepreneurial intentions. The research on PBL online learning recommendation system shows that the proposed recommendation algorithm is superior to the traditional recommendation algorithm in both roots mean square error value and mean absolute error value on both datasets. The proposed method provides a new idea of reform and innovation to cultivate social security law professionals and the cultivation of the reserve model.


Characterization and cellular localization of human 5-lipoxygenase and its protein isoforms 5-LOΔ13, 5-LOΔ4 and 5-LOp12.
Human 5-lipoxygenase (5-LO-WT) initiates the leukotriene (LT) biosynthesis. LTs play an important role in diseases like asthma, atherosclerosis and in many types of cancer. In this study, we investigated the 5-LO isoforms 5-LO∆13, 5-LO∆4 and 5-LOp12, lacking the exons 13, 4 or a part of exon 12, respectively. We were able to detect the mRNA of the isoforms 5-LO∆13 and 5-LOp12 in B and T cell lines as well as in primary B and T cells and monocytes. Furthermore, we found that expression of 5-LO and particularly of the 5-LO∆13 and 5-LOp12 isoforms is increased in monocytes from patients with rheumatoid arthritis and sepsis. Confocal microscopy of HEK293T cells stably transfected with tagged 5-LO-WT and/or the isoforms revealed that 5-LO-WT is localized in the nucleus whereas all isoforms are located in the cytosol. Additionally, all isoforms are catalytically inactive and do not seem to influence the specific activity of 5-LO-WT. S271A mutation in 5-LO-WT and treatment of the cells with sorbitol or KN-93/SB203580 changes the localization of the WT enzyme to the cytosol. Despite colocalization with the S271A mutant, the isoforms did not affect LT biosynthesis. Analysis of the phosphorylation pattern of 5-LO-WT and all the isoforms revealed that 5-LOp12 and 5-LO∆13 are highly phosphorylated at Ser271 and 5-LOp12 at Ser523. Furthermore, coexpression of the isoforms inhibited or stimulated 5-LO-WT expression in transiently and stably transfected HEK293T cells suggesting that the isoforms have other functions than canonical LT biosynthesis.


Late Onset of CSF Rhinorrhea in a Postoperative Transsphenoidal Surgery Patient Following Robotic-Assisted Abdominal Hysterectomy.
Cerebrospinal fluid (CSF) leak is the most commonly encountered perioperative complication in transsphenoidal surgery for pituitary lesions. Direct closure with a combination of autologous fat, local bone, and/or synthetic grafts remains the standard of care for leaks encountered at the time of surgery as well as postoperatively. The development of the vascularized nasoseptal flap as a closure technique has increased the surgeon's capacity to correct even larger openings in the dura of the sella as well as widely exposed anterior skull base defects. Yet these advances in the technical nuances for management of post-transsphenoidal CSF leak are useless without the ability to recognize a CSF leak by physical examination, clinical history, biochemical testing, or radiographic assessment. Here, we report a case of a patient who developed a CSF leak 28 years after transsphenoidal surgery, precipitated by a robotic-assisted hysterectomy during which increased intra-abdominal pressure and steep Trendelenberg positioning were both factors. Given the remote nature of the patient's transsphenoidal surgery and relative paucity of data regarding such a complication, the condition went unrecognized for several months. We review the available literature regarding risk and pathophysiology of CSF leak following abdominal surgery and propose the need for increased vigilance in identification of such occurrences with the increasing acceptance and popularity of minimally invasive abdominal and pelvic surgeries as standards in the field.


Application to routine analysis of a method to determine multiclass pesticide residues in fresh vegetables by gas chromatography/tandem mass spectrometry.
The use of gas chromatography/tandem mass spectrometry (GC/MS/MS) applied to determine multiple pesticide residues in fresh vegetables has been thoroughly studied. A single injection method to detect, confirm and quantify 54 multiclass pesticides has been developed and applied in a routine analysis laboratory. The proposed method consists of a rapid extraction of 15 g of vegetable sample with dichloromethane. An additional clean-up step is not necessary even when injecting 10 microL of extract. Instead the gas chromatograph was fitted with a carbofrit inserted into the glass liner and a guard column. In addition, the detection mode chosen (MS/MS) provides additional selectivity. The method has been validated and applied to 1300 samples in a routine laboratory following specified quality criteria. The recovery efficiencies obtained for all the pesticides ranged between 70.2 and 110.8% at two different fortification levels. The relative standard deviation for quantification (RSD) was lower than 16.7% for all the compounds. Important experimental parameters, such as the conditioning of carbofrit, overload of the analytical column, and cleanliness of the ion trap, were evaluated for their influence on the performance of the method.


Early tracheostomy in closed head injuries: experience at a tertiary center in a developing country--a prospective study.
An important factor contributing to the high mortality in patients with severe head trauma is cerebral hypoxia. The mechanical ventilation helps both by reduction in the intracranial pressure and hypoxia. Ventilatory support is also required in these patients because of patient's inability to protect the airway, persistence of excessive secretions, and inadequacy of spontaneous ventilation. Prolonged endotracheal intubation is however associated with trauma to the larynx, trachea, and patient discomfort in addition to requirement of sedatives. Tracheostomy has been found to play an integral role in the airway management of such patients, but its timing remains subject to considerable practice variation. In a developing country like India where the intensive care facilities are scarce and rarely available, these critical patients have to be managed in high dependency cubicles in the ward, often with inadequately trained nursing staff and equipment to monitor them. An early tracheostomy in the selected group of patients based on Glasgow Coma Score(GCS) may prove to be life saving. Against this background a prospective study was contemplated to assess the role of early tracheostomy in patients with isolated closed head injury. The series consisted of a cohort of 50 patients admitted to the surgical emergency with isolated closed head injury, that were not considered for surgery by the neuro-surgeon or shifted to ICU, but had GCS score of less than 8 and SAPS II score of more than 50. First 50 case records from January 2001 that fulfilled the criteria constituted the control group. The patients were managed as per ATLS protocol and intubated if required at any time before decision to perform tracheostomy was taken. These patients were serially assessed for GCS (worst score of the day as calculated by senior surgical resident) and SAPS scores till day 15 to chart any changes in their status of head injuries and predictive mortality. Those patients who continued to have a GCS score of <8 and SAPS score of >50 for more than 24 hours (to rule out concussion or recovery) underwent tracheostomy. All these patients were finally assessed for mortality rate and hospital stay, the statistical analysis was carried out using SPSS10 version. The final outcome (in terms of mortality) was analyzed utilizing chi-square test and p value <0.05 was considered significant. At admission both tracheostomy and non-tracheostomy groups were matched with respect to GCS score and SAPS score. The average day of tracheostomy was 2.18 +/- 1.0038 days. The GCS scores on days 1, 2, 3, 4, 5, 10 between tracheostomy and non-tracheostomized group were comparable. However the difference in the GCS scores was statistically significant on day 15 being higher in the tracheostomy group. Thus early tracheostomy was observed to improve the mortality rate significantly in patients with isolated closed head injury. It may be concluded that early tracheostomy is beneficial in patients with isolated closed head injury which is severe enough to affect systemic physiological parameters, in terms of decreased mortality and intubation associated complications in centers where ICU care is not readily available. Also, in a selected group of patients, early tracheostomy may do away with the need for prolonged mechanical ventilation.


Altered fibroblast proliferation and apoptosis in diabetic gingival wounds.
Although it is known that diabetes impairs oral wound healing, relatively little is known about the cellular parameters affected, particularly in connective tissue. This study investigated the hypothesis that diabetes impairs connective tissue formation in healing gingiva, and that impaired healing is associated with factors that decrease fibroblast numbers. Full-thickness wounds were created in the palatal gingiva of type 1 and type 2 diabetic and normoglycemic mice. Five days after wounding, diabetic mice had less epithelial wound coverage, less new connective tissue formation, and reduced fibroblast density (p < 0.05). This occurred with increased numbers of caspase-3- and TUNEL-positive fibroblasts, decreased fibroblast proliferation, increased nuclear translocation of the pro-apoptotic transcription factor FOXO1, and increased numbers of polymorphonuclear leukocytes, all of which were significant (p < 0.05). The results suggest that diabetes may decrease fibroblast numbers through increased apoptosis and reduced proliferation, both of which may be mediated through increased activation of FOXO1.


Perceptual and imaginary mixtures in chemosensation.
D. Algom and W.S. Cain (1991) reported similar interaction patterns for perceived and imaginary mixtures of odorants. However, their experimental design did not allow sensitive statistical testing to demonstrate differences between conditions. Three experiments on 16 mixtures of sucrose-citric acid mixtures yielded significantly different interaction pattern for perceived and imaginary mixtures. Inconsistencies in the degrees of suppression in the imaginary condition suggested that participants did not base their responses on the inspection of a mental image but on incomplete implicit or explicit knowledge of sensory interactions. Participants knew the phenomenon of mixture suppression and knew that its effects were level dependent, but they were unable to predict the exact intensity of a mixture on the basis of the intensities of its unmixed components.


Cardiac Surgery at the Cleveland Clinic.
Founded in 1921 as a multidisciplinary physician-based practice with an emphasis on teamwork, Cleveland Clinic developed a focus on cardiothoracic diseases early in its history. From the development of coronary angiography and coronary artery bypass grafting to more recent advances in the management of heart valve disease, Cleveland Clinic surgeons have sought to contribute to cardiac surgery through a combination of innovation and careful analysis of patient outcomes.


Prognostic factors of intrahepatic cholangiocarcinoma after hepatic resection: univariate and multivariate analysis.
Intrahepatic cholangiocarcinoma is clinicopathologically distinct from hepatocellular carcinoma and hilar cholangiocarcinoma, and the prognostic factors after hepatic resection of these rare tumors are not well documented. The aim of this study was to evaluate prognostic factors of intrahepatic cholangiocarcinoma after hepatic resection. We retrospectively studied 20 consecutive patients with intrahepatic cholangiocarcinoma who underwent hepatectomy over a 15-year period from 1984 to 1998. Fifteen prognostic factors were evaluated for their association with overall and disease-free survivals in univariate and multivariate analysis (Cox's proportional hazards model). Eighty percent of the resected patients had major hepatectomy. Operative morbidity and mortality rates were 30% and 0%, respectively. Four patients (20%) survived more than 5 years without recurrence after hepatic resection. The 1-year, 3-year, and 5-year overall or disease-free survival rate after hepatic resection were 56.0% or 49.5%, 43.8% or 43.3%, and 43.8% or 37.3%, respectively. Univariate analysis showed young age and periductal invasion tumor or the presence of vascular invasion, lymphatic invasion, and lymph node metastasis as significant poor prognostic predictors contributing overall and disease-free survivals. Multivariate analysis revealed only lymph node metastasis as an independent prognostic factor affecting disease-free survival. During the same time, 17 unresectable patients were treated by intrahepatic arterial infusion chemotherapy (12), systemic chemotherapy (4), or radiation (1). Median overall survival time in resected patients (16 months) was significantly better than in unresectable patients (5 months) (P = 0.005). Hepatic resection remains to be the best current therapeutic option. The prognosis after hepatic resection for intrahepatic cholangiocarcinoma was determined by lymph node metastasis. New adjuvant chemotherapy after surgery is imperative for such patients.


Performance study and analysis method for a new-generation MIPAS experiment.
This study fits within the ongoing activities aimed at filling the lack of an operational IR limb sounder after the ENVISAT fault. Notably, we report the performance of a possible evolution of the MIPAS experiment. The strategy proposed for the new experiment (that we denote as MIPAS2k) is derived from the PREMIER infrared limb sounder (IRLS) and relies on both 1D array detector technology and reduction of the spectral resolution to achieve dense atmospheric sampling. We define observation parameters and report, as an example, the performance obtained by MIPAS2k when measuring O₃fields. The information load (IL) analysis was exploited to assess the sensitivity of MIPAS2k and to select optimal spectral intervals for retrieval tests on simulated observations of the new experiment. The results of the IL analysis suggest a new approach to the retrieval strategy (denoted as full-2D) in which the unknown parameter is no longer an element of the altitude profile but the constant value taken by the atmospheric quantity within a parcel (denoted as "clove") of the 2D discretization. We demonstrate that the clove homogeneity assumption generates errors that are below the spectral noise of MIPAS2k when an appropriate clove thickness is used. Full-2D retrievals have been carried out on MIPAS2k simulated observations corresponding to a high resolution model atmosphere. We report a test case on O₃ VMR in which the retrieval precision is better than 5% between 20 and 40 km and better than 30% in the upper troposphere-lower stratosphere. We test the ability of MIPAS2k to reconstruct a fine O₃ structure present in the model atmosphere and we show how this structure would have been represented by MIPAS when measuring the same scenario. We have estimated the spatial resolution of MIPAS2k products by means of the perturbation approach that, in simulated retrievals, can be adopted to evaluate the averaging kernel of the retrieval parameters. For O₃ we have found the estimates of 200 km and 2.5 km for the horizontal and vertical resolutions respectively.


Decline in native kidney function in liver transplant recipients is not associated with BK virus infection.
BK virus (BKV) infection is an established cause of allograft dysfunction in renal transplant recipients. The relationship between BKV infection and chronic kidney disease (CKD) post-orthotopic liver transplantation (OLT) is not well understood. This study aimed to determine the prevalence of BKV infection, its relationship to CKD and renal function loss over time in patients receiving OLT. Prevalence of BK viruria and viremia were studied in 41 post-OLT patients after a mean 6.5 +/- 4.7 years posttransplantation. Renal function was assessed using estimated glomerular filtration rate (eGFR) calculated from the yearly serum creatinine levels using the Modification of Diet in Renal Disease (MDRD) formula. Polymerase chain reaction (PCR) was performed for detection of BKV DNA in urine and plasma. BK viruria was present in 24.2% of patients, but none of these OLT recipients had detectable BK viremia. Decoy cells in the urine were found in 9.7% patients, although none of these patients had BK viruria. CKD, defined as eGFR <60 mL/minute/1.73 m(2), was found in 83% of OLT recipients. The yearly decline in eGFR was -6.9 +/- 17 and -9.2 +/- 18 mL/minute/year in BK viruria-positive and BK viruria-negative patients, respectively (P = 0.39). There was no relationship between the presence or absence of BK viruria and either current eGFR, yearly decline in eGFR, number and type of immunosuppressive agents, or etiology of liver failure. In OLT recipients, BK viruria is not associated with BK viremia or native kidney dysfunction. It appears that the most probable pathway for the development of BKV nephropathy requires a second hit, such as kidney inflammation, kidney ischemia, or donor-recipient human leukocyte antigen mismatch.


CcpA mutants with differential activities in Bacillus subtilis.
CcpA is the master regulator for carbon catabolite regulation in Bacillus subtilis and regulates more than 300 genes by repression or activation. To revealthe effects of different functional domains of CcpA on various regulatory modes, we compared the activities of CcpA point mutants in activation (alsS, ackA) and repression (xynP, gntR). CcpA variants mutated at residues in the HPrSerP-binding region without allosteric functions are inactive. On the other hand, CcpA variants mutated at residues that change their conformation upon HPrSerP or CrhP binding regulate only ackA. Another set of mutants with alterations in the corepressor-binding region show glucose-independent regulation of xynP. The data presented here demonstrate the involvement of HPrSerP and/or CrhP in activation of ackA and alsS by CcpA. Furthermore, these data also indicate that activation and repression mediated by CcpA may utilize different conformational changes of the protein.


Use of progressive fixed-ratio procedures in the assessment of intracranial reinforcement.
Six rats with electrodes chronically implanted in septal or hypothalamic sites were tested for intracranial reinforcement on a progressive fixed-ratio schedule. Two variations of this schedule were also examined and compared. Functions relating the highest level of stable fixed-ratio responding to a wide range of stimulus currents were, unlike those derived from continuous reinforcement rates, monotonic at all stimulation sites tested. One of the procedures described, in particular, is quite sensitive to intracranial reinforcement parameters, provides a reliable technique for within-session assays of these parameters, and successfully avoids many problems commonly encountered with administration of central stimulation on a continuous reinforcement schedule.


Contribution of Regulatory T Cell Methylation Modifications to the Pathogenesis of Allergic Airway Diseases.
Regulatory T (Treg) cells are a subtype of CD4+ T cells that play a significant role in the protection from autoimmunity and the maintenance of immune tolerance via immune regulation. Epigenetic modifications of Treg cells (i.e., cytosine methylation at the promoter region of the transcription factor, Forkhead Box P3) have been found to be closely associated with allergic diseases, including allergic rhinitis, asthma, and food allergies. In this study, we highlighted the recent evidence on the contribution of epigenetic modifications in Treg cells to the pathogenesis of allergic diseases. Moreover, we also discussed directions for future clinical treatment approaches, with a particular emphasis on Treg cell-targeted therapies for allergic disorders.


[Reference value and cut-off value for diagnosis of insulin resistance in type 2 diabetes mellitus].
The homeostasis model assessment-insulin resistance(HOMA-IR) index has been proposed to assess insulin resistance, which plays an important role in the pathogenesis of type 2 diabetes mellitus. However, it has not generally introduced into the outpatient care in Japan, because of lack in definite reference values. In this paper we studied the precision in the assay of immuno-reactive insulin and then the HOMA-IR index was determined in 90 healthy individuals and 281 type 2 diabetic patients. The reference value was calculated to be 1.77 +/- 0.44(mean +/- SD) in healthy individuals without obesity. Receiver operating characteristic curve analysis gave the cut-off values discriminating between healthy and diabetic subjects to be 2.53, 3.50 and 3.00 in non-obese, obese and total individuals, respectively. These values should be available for the diagnosis of insulin resistance in type 2 diabetes mellitus.


Electrospinning preparation and photoluminescence properties of Y3Al5O12:Tb3+ nanostructures.
Novel nanostructures of Y3Al5O12:Tb(3+) (denoted as YAG:Tb(3+) for short) nanobelts and nanofibers were fabricated by calcination of the respective electrospun PVP/[Y(NO3)3 + Tb(NO3)3 + Al(NO3)3] composite nanobelts and nanofibers. YAG:Tb(3+) nanostructures are cubic in structure with a space group of Ia 3d. The thickness and width of the YAG:7%Tb(3+) nanobelts are respectively ca. 125 nm and 5.9 ± 0.3 m, and the diameter of YAG:7%Tb(3+) nanofibers is 166.0 ± 20 nm (95% confidence level). The YAG:Tb(3+) nanostructures emit predominantly at 544 nm from the energy levels transition of (5) D4 → (7) F5 of Tb(3+) ions under the excitation of 274-nm ultraviolet light. It was found that the optimum doping molar concentration of Tb(3+) ions for YAG:Tb(3+) nanostructures was 7%. Compared with YAG:7%Tb(3+) nanofibers, YAG:7%Tb(3+) nanobelts exhibit a stronger photoluminescence (PL) intensity under the same doping concentration. Commission International de l'Eclairage (CIE) analysis demonstrates that the emitting colors of YAG:Tb(3+) nanostructures are located in the green region and color-tuned luminescence can be obtained by changing the doping concentration of Tb(3+) and morphologies of the nanostructures, which could be applied in the field of optical telecommunication and optoelectronic devices. The possible formation mechanisms of YAG:Tb(3+) nanobelts and nanofibers are also proposed.


Human thymic epithelial cells present superantigens to T-cell lines and thymocytes.
It is generally accepted that thymic epithelial cells (TEC) act as accessory cells in positive selection of pre-T cells. However, our knowledge of the antigen presentation and accessory cell function to human TEC is limited. Here we present results obtained by the use of serum-free cultured human TEC, showing that IFN-gamma-treated TEC are able to support T-cell-mediated responses to the bacterial superantigens (Sag) SEA and SEB, even at very low Sag concentrations. T-cell responses to TEC-presented Sags were dependent on the presence of the adhesion molecules ICAM-1, ICAM-2, LFA-1, and LFA-3, but not on CD4 and CD8 molecules. There is a low but significant expression of B7 molecules on human TEC, and treatment of TEC with anti-B7.1 and anti-B7.2 antibodies before Sag pulsing leads to decreased Sag responses, indicating a significant importance of B7 molecules on TEC. Both CD4+ T-cell lines and CD4+ as well as CD8+ subpopulations of thymocytes showed significant responses, whereas nonseparated thymocytes, CD4+8+, and CD4-CD8- thymocytes did not respond or showed very low responses. In conclusion, the present results demonstrate that cultured human TEC are able to present Sag to thymocytes.


Determinants of Stunting at 6 Weeks in the Northern Cape Province, South Africa.
The first 1,000 days from conception to 24 months is a critical period for healthy growth and development. In South Africa, stunting (weight-for-length below -2SD from the WHO reference mean) is a major public health issue with significant health consequences. We determined associations between demographic, health, and anthropometric indicators of mothers and their infants. A cross-sectional study was conducted in the Northern Cape. All mothers with 5- to 7-week-old babies visiting PHC facilities were invited to participate. A questionnaire was completed in a structured interview with each mother. Age and length of the baby at 6 weeks were used to determine stunting, while the weight and height of the mother were measured for body mass index (BMI). Eight hundred questionnaires were completed in 92 facilities. The median age of mothers was 26 years (IQR 20-30 years) and 44.9% were married. Only 40.1% had completed school or tertiary education and almost 40% relied on a government grant as the main source of income. Two-thirds (64.9%) had not planned the pregnancy and 17% were on antiretroviral therapy (ART). More than a quarter (26.1%) smoked cigarettes or used snuff during pregnancy, while 9.4% drank alcohol. At 6 weeks, 31% of boys and 14% of girls had a length-for-age below the WHO reference values, while 25.4% of mothers were classified as obese and 24.6% as overweight. More than 70% had a waist circumference above 80 cm. Significantly more mothers with stunted babies weighed less [-6 kg; -1 kg] and were shorter [-4 cm; -1 cm] than mothers with babies who were not stunted. Compared to babies who were not stunted, significantly more babies of mothers who lived in informal housing [-19.7%; -3.2%], relied on a grant [-19.7%; -3.2%], smoked/ snuffed [7.6%; 23.5%], and used alcohol during pregnancy [0.3%; 11.5%] were stunted. The following factors significantly increased the risk of having a stunted baby at 6 weeks: living in informal housing vs. formal housing (RR: 0.68, 95% CI [0.5; 0.9]); smoking or using snuff during pregnancy (RR: 1.74, 95% CI [1.3; 2.3]); using alcohol during pregnancy (RR: 1.5, 95% CI [1.1; 2.2]); both smoking and using alcohol during pregnancy (RR: 1.97, 95% CI [1.4; 2.9]). We confirmed the coexistence of under- and over-nutrition among mothers and their babies, possibly indicating that stunting in childhood may predispose to overweight and obesity in adulthood in a vicious cycle that affects generation after generation. Interventions aimed at poverty alleviation and encouraging healthy lifestyles with an emphasis on healthy eating, smoking cessation and abstaining from alcohol before pregnancy are urgently required.


Use of Blue-Green Fluorescence and Thermal Imaging in the Early Detection of Sunflower Infection by the Root Parasitic Weed Orobanche cumana Wallr.
Although the impact of Orobanche cumana Wallr. on sunflower (Helianthus annuus L.) becomes evident with emergence of broomrape shoots aboveground, infection occurs early after sowing, the host physiology being altered during underground parasite stages. Genetic resistance is the most effective control method and one of the main goals of sunflower breeding programmes. Blue-green fluorescence (BGF) and thermal imaging allow non-destructive monitoring of plant diseases, since they are sensitive to physiological disorders in plants. We analyzed the BGF emission by leaves of healthy sunflower plantlets, and we implemented BGF and thermal imaging in the detection of the infection by O. cumana during underground parasite development. Increases in BGF emission were observed in leaf pairs of healthy sunflowers during their development. Lower BGF was consistently detected in parasitized plants throughout leaf expansion and low pigment concentration was detected at final time, supporting the interpretation of a decrease in secondary metabolites upon infection. Parasite-induced stomatal closure and transpiration reduction were suggested by warmer leaves of inoculated sunflowers throughout the experiment. BGF imaging and thermography could be implemented for fast screening of sunflower breeding material. Both techniques are valuable approaches to assess the processes by which O. cumana alters physiology (secondary metabolism and photosynthesis) of sunflower.


Disparity in childhood immunizations.
Incomplete immunization coverage is common in low-income families and Aboriginal children in Canada. To determine whether child immunization coverage rates at two years of age were lower in low-income neighbourhoods of Saskatoon, Saskatchewan. Parents who were and were not behind in child immunization coverage were contacted to determine differences in knowledge, beliefs and opinions on barriers and solutions. A multivariate regression model was designed to determine whether Aboriginal cultural status was associated with being behind in childhood immunizations after controlling for low-income status. Reviewing the past five years in Saskatoon, the six low-income neighbourhoods had complete child immunization coverage rates of 43.7% (95% CI 41.2 to 45.9) for measles-mumps-rubella, and 42.6% (95% CI 40.1 to 45.1) for diphtheria, pertussis, tetanus, polio and Haemophilus influenzae type B. The five affluent neighbourhoods had 90.6% (95% CI 88.9 to 92.3) immunization coverage rates for measles-mumps-rubella, and 78.6% (95% CI 76.2 to 81.0) for diphtheria, pertussis, tetanus, polio and H influenzae type B. Parents who were behind in immunization coverage for their children were more likely to be single, of Aboriginal or other (non-Caucasian or non-Aboriginal) cultural status, have lower family income and have significant differences in reported beliefs, barriers and potential solutions. In the final regression model, Aboriginal cultural status was no longer associated with lower immunization status. Child immunization coverage rates in Saskatoon's six low-income neighbourhoods were approximately one-half the rate of the affluent neighbourhoods. The covariates with the strongest independent association with complete childhood immunization status were low income and other cultural status. Aboriginal cultural status was not associated with low child immunization rates after controlling for income status.


Influence of tumor estrogen and progesterone receptor levels on the response to tamoxifen and chemotherapy in primary breast cancer.
In 1977 the National Surgical Adjuvant Breast and Bowel Project initiated a prospectively randomized clinical trial for women with primary operable breast cancer and positive axillary nodes. In this study 1891 patients were randomized to receive L-phenylalanine mustard and 5-fluorouracil (PF) either with or without tamoxifen (T). In this interim report findings are presented concerning disease-free survival (DFS) and survival as related to age and to estrogen receptor (ER) and/or progesterone receptor (PR) content of the tumor. The median follow-up time is 3 yr. Patients 50 yr of age or older with either 1-3 or more than 3 positive axillary nodes had a markedly longer disease-free survival on PFT than did those receiving PF adjuvant therapy (p less than 0.001). The effectiveness of PFT was related to the levels of tumor receptors. Patients 50 yr old or more with both tumor ER and PR levels of 10 fmole or more ("high") displayed the greatest benefit in disease-free survival from PFT (p = 0.004). Analyses by age indicated that it is more appropriate to divide patients of 50 yr or older into two age groups, 50-59 and 60-70 yr old. In the former the survival results were poorer on PFT when tumor PR was low, whereas, regardless of receptor levels, those 60-70 yr old experienced an advantage on PFT. In women under 50 yr of age, there was no difference in disease-free survival (p = 0.64), but survival results favored the PF over the PFT treated (p = 0.06). Patients under 50 yr with tumor ER and PR levels under 10 fmole ("low") had a poorer survival when given PFT (p = 0.003). Those whose tumors demonstrated a high ER and a low PR also had a shorter survival on PFT (p = 0.01). The observation of no benefit in younger patients when both receptor levels were high, but a benefit in older patients with receptor-poor tumors, indicates that, at least according to the conditions of this study, the difference between the two age groups cannot be explained by the association of age with receptor content. Multivariate analyses considered the effects of the number of positive nodes, age, ER, and PR. They support the conclusion that, while nodes and ER exert strong prognostic influences in both PF- and PFT-treated patients, the PR content of tumors is a stronger predictor of the effectiveness of PFT therapy than is ER content.(ABSTRACT TRUNCATED AT 400 WORDS)


Surfactant-Assisted Synthesis of Praseodymium Orthovanadate Nanofiber-Supported NiFe-Layered Double Hydroxide Bifunctional Catalyst: The Electrochemical Detection and Degradation of Diphenylamine.
Physiological storage disorders are caused by ineffective post-harvest handling of horticultural crops, particularly fruits. To address these post-harvest concerns, diphenylamine (DPAH•+) is widely used as a preservative to prevent fruit degradation and surface scald during storage around the world. Humans are negatively affected by the use of high concentrations of DPAH•+ because of the various health complications related to its exposure. As a result, accurate detection and quantification of DPAH•+ residues in treated fruits are critical. Rare earth metal orthovanadates, which have excellent physical and chemical properties, are potential materials for electrochemical sensors in this area. Herein, we present a simple and direct ultrasonication technique for the surfactant-assisted synthesis of praseodymium orthovanadate (PrVO4 or PrV) loaded on nickel iron layered double hydroxide (NiFe-LDH) synthesized with deep eutectic solvent assistance, as well as its application as an effective catalyst in the detection and degradation of DPAH•+ in fruits and water samples. The current work presents supreme electrochemical features of a PrV@NiFe-LDH-modified screen-printed carbon electrode (SPCE) where cetyltrimethylammonium bromide (CTAB) surfactant-driven fabrication of PrV directs the formation of highly qualified engineered structures and the deep eutectic solvent based green synthesis of NiFe-LDH creates hierarchical lamellar structures following the principles of green chemistry. PrV and NiFe-LDH combine to produce a synergistic effect that improves the number of active sites, charge transfer kinetics, and electronic conductivity. Differential pulse voltammetry analysis of PrV@NiFe-LDH/SPCE reveals a dynamic working range (0.005-226.26 μM), increased sensitivity (133.13 μA μM-1 cm-2), enhanced photocatalytic activity, and low detection limit (0.001 μM), which are considered significant when compared with the former reported electrodes in the literature for the determination of DPAḢ+ for its real-time applications.


Cytotoxic T lymphocyte associated antigen 4 expression predicts poor prognosis in luminal B HER2-negative breast cancer.
Cytotoxic T lymphocyte associated antigen 4 (CTLA-4) serves an important role in inhibiting anti-tumor immune response in the majority of solid tumors. However, a limited number of studies reported the function of CTLA-4 in luminal B HER2-negative breast cancer. Immunohistochemistry was performed to evaluate the expression of tumor and interstitial CTLA-4 in luminal B HER2-negative breast cancer tissues. The percentage of patients with tumor and interstitial CTLA-4+ was 41.2% (42/102) and 46.1% (47/102), respectively. There was a positive association between tumor CTLA-4 expression and interstitial CTLA-4 expression (P<0.05). The disease-free survival (DFS) of the tumor CTLA-4+ group was significantly shorter compared with patients with tumor CTLA-4- (mean, 89.070 vs. 39.022 months; P<0.0001). Additionally, the DFS of interstitial CTLA-4+ group was shorter compared with the interstitial CTLA-4- group (mean, 85.526 vs. 46.574 months; P<0.0001). Tumor and interstitial CTLA-4 expression may have prognostic predicting value in luminal B HER2-negative breast cancer. The present study may provide the basis for the use of a CTLA-4 blocker in patients with luminal B HER2-negative breast cancer.


Factors influencing the knowledge, attitude, and practices of police personnel toward dengue fever in Kathmandu, Nepal.
Dengue fever is a significant public health problem in Nepal, and police personnel are considered to play a crucial role in preventing and controlling dengue fever. This study aimed to assess the factors that influence the knowledge, attitudes, and practices of police personnel toward dengue in Kathmandu, Nepal. The study design was a descriptive cross-sectional study among 422 police personnel, where data were collected using self-administered questionnaires. Bi-variate analysis and multivariate analysis were used to examine the association between sociodemographic factors and environmental factors with knowledge, attitude, and practices of dengue. The study found that the knowledge, attitude, and practice toward dengue prevention was 58%, 46%, and 75%, respectively. The study found that family history of dengue (AOR = 2.78, 95% CI = 1.38-5.6), owning bed nets (AOR = 2.13, 95% CI = 1.04-4.35) and having covered water storage containers (AOR = 2.99, 95% CI = 1.74-5.13) were associated with higher odds of knowledge on dengue. Having family history of dengue (AOR = 2.45, 95% CI = 1.24-4.87) and the presence of broken glasses or discarded plastic bottles in the house (AOR = 2.07, 95% CI = 1.93-5.36) were associated with attitude on dengue. Knowledge on dengue was associated with higher odds of attitude (AOR = 3.3, 95% CI = 2.09-5.36) and practices (AOR = 3.21, 95% CI = 1.93, 5.36). The study identified specific factors associated with knowledge, attitude, and practices toward dengue prevention. The study concluded that regular training and awareness-raising activities are needed to improve their knowledge, attitudes, and practices toward dengue.


Impact of the surface recombination on InGaN/GaN-based blue micro-light emitting diodes.
In this work, the size-dependent effect for InGaN/GaN-based blue micro-light emitting diodes (µLEDs) is numerically investigated. Our results show that the external quantum efficiency (EQE) and the optical power density drop drastically as the device size decreases when sidewall defects are induced. The observations are owing to the higher surface-to-volume ratio for small µLEDs, which makes the Shockley-Read-Hall (SRH) non-radiative recombination at the sidewall defects not negligible. The sidewall defects also severely affect the injection capability for electrons and holes, such that the electrons and holes are captured by sidewall defects for the SRH recombination. Thus, the poor carrier injection shall be deemed as a challenge for achieving high-brightness µLEDs. Our studies also indicate that the sidewall defects form current leakage channels, and this is reflected by the current density-voltage characteristics. However, the improved current spreading effect can be obtained when the chip size decreases. The better current spreading effect takes account for the reduced forward voltage.


Is there an entity of chemically induced BCR-ABL-positive chronic myelogenous leukemia?
Advances in the therapy of malignancy have been accompanied by an increased frequency of cases of secondary acute myelogenous leukemia and related clonal cytopenias and oligoblastic (subacute) myelogenous leukemia (myelodysplastic syndromes). The acute myelogenous leukemia incidence can be increased by high-dose acute ionizing radiation exposure, alkylating agents, topoisomerase II inhibitors, possibly other DNA-damaging therapeutic agents, heavy, prolonged cigarette smoking, and high dose-time exposure to benzene, the latter less frequently seen in industrialized countries with worksite regulations. Acute myelogenous leukemia and myelodysplastic syndromes may result from innumerable primary types of chromosome damage. In the case of chronic myelogenous leukemia, a specific break in chromosome bands 9q34 and 22q11 must occur to result in the causal fusion oncogene (BCR-ABL). A review of 11 studies of the chromosomal abnormalities found in presumptive cases of cytotoxic therapy-induced leukemia and of 40 studies of the subtypes of leukemia that occur following cytotoxic therapy for other cancers has not provided evidence of an increased risk for chemically induced BCR-ABL-positive chronic myelogenous leukemia. Studies of the effects of alkylating agents, topoisomerase inhibitors, and benzene on chromosomes of hematopoietic cells in vitro, coupled with the aforementioned epidemiological studies of secondary leukemia after cytotoxic therapy or of persons exposed to high dose-time concentrations of benzene in the workplace, do not indicate a relationship among chemical exposure, injury to chromosome bands 9q34 and 22q11, and an increased risk for BCR-ABL-positive chronic myelogenous leukemia.


Service evaluation project - Are local recommendations for onward referral to a specialist menopause clinic required to translate guidelines into practice?
Objective Referral audit - are local recommendations required to translate guideline to practice? Study design In total, 50 consecutive, anonymised referral letters reviewed during the initial consultation in a specialist menopause clinic; the reasons for referral along with the patient's age and the source of referral were analysed. Results Several common reasons for referral were identified. Sexual dysfunction, including loss of libido and dyspareunia, resulted in 11 (22%) referrals. Ten (20%) women were troubled by persistent symptoms or side effects from HRT; 9 (18%) women were referred before hormone replacement therapy was discussed or commenced; 7 (14%) women seeking advice for their menopausal symptoms had a family or personal history of cancer; 5(10%) were migraineurs; 2(4%) women had premature ovarian insufficiency; 2(4%) were denied hormone replacement therapy because of concern about venous thromboembolism risk; and 4 (8%) had miscellaneous medical disorders. Over 25% of referrals were older than 60. Conclusion Menopausal symptoms are predominately dealt with in primary care where advice and support is needed. National Institute for Health Care and Excellence published guidance regarding onward referral to a specialist menopause clinic, which is vague and referral patterns are haphazard. Our audit highlighted areas of clinical uncertainty and formed the basis for providing local pre-referral information and advice. Some of the information provided is quite detailed and aimed at healthcare professionals with a special interest in menopause. Further training is now required to improve the quality of referrals. The diversity and complexity of some referrals illustrates the need both for a menopause specialist and clear pathways for further advice or referral within each region.


Infarcts and ischemia in the abdomen: an imaging perspective with an emphasis on cross-sectional imaging findings.
Infarcts and ischemia of abdominal organs may present with acute abdominal pain, and early diagnosis is crucial to prevent morbidity and mortality. Unfortunately, some of these patients present in poor clinical conditions to the emergency department, and imaging specialists are crucial for optimal outcomes. Although the radiological diagnosis of abdominal infarcts is often straightforward, it is vital to use the appropriate imaging modalities and correct imaging techniques for their detection. Additionally, some non-infarct-related abdominal pathologies may mimic infarcts, cause diagnostic confusion, and result in delayed diagnosis or misdiagnosis. In this article, we aimed to outline the general imaging approach, present cross-sectional imaging findings of infarcts and ischemia in several abdominal organs, including but not limited to, liver, spleen, kidneys, adrenals, omentum, and intestinal segments with relevant vascular anatomy, discuss possible differential diagnoses and emphasize important clinical/radiological clues that may assist radiologists in the diagnostic process.


Tuning CO2 uptake and reversible iodine adsorption in two isoreticular MOFs through ligand functionalization.
The synthesis and characterization of two isoreticular metal-organic frameworks (MOFs), {[Cd(bdc)(4-bpmh)]}n⋅2 n(H2O) (1) and {[Cd(2-NH2bdc)(4-bpmh)]}n⋅2 n(H2O) (2) [bdc = benzene dicarboxylic acid; 2-NH2bdc = 2-amino benzene dicarboxylic acid; 4-bpmh = N,N-bis-pyridin-4-ylmethylene-hydrazine], are reported. Both compounds possess similar two-fold interpenetrated 3D frameworks bridged by dicarboxylates and a 4-bpmh linker. The 2D Cd-dicarboxylate layers are extended along the a-axis to form distorted square grids which are further pillared by 4-bpmh linkers to result in a 3D pillared-bilayer interpenetrated framework. Gas adsorption studies demonstrate that the amino-functionalized MOF 2 shows high selectivity for CO2 (8.4 wt % 273 K and 7.0 wt % 298 K) over CH4 , and the uptake amounts are almost double that of non-functional MOF 1. Iodine (I2 ) adsorption studies reveal that amino-functionalized MOF 2 exhibits a faster I2 adsorption rate and controlled delivery of I2 over the non-functionalized homolog 1.


Multiparametric MRI-targeted TRUS prostate biopsies using visual registration.
Prebiopsy multiparametric prostate MRI (mp-MRI), followed by transrectal ultrasound-guided (TRUS-G) target biopsies (TB) of the prostate is a key combination for the diagnosis of clinically significant prostate cancers (CSPCa), to avoid prostate cancer (PCa) overtreatment. Several techniques are available for guiding TB to the suspicious mp-MRI targets, but the simplest, cheapest, and easiest to learn is "cognitive," with visual registration of MRI and TRUS data. This review details the successive steps of the method (target detection, mp-MRI reporting, intermodality fusion, TRUS guidance to target, sampling simulation, sampling, TRUS session reporting, and quality insurance), how to optimize each, and the global indications of mp-MRI-targeted biopsies. We discuss the diagnostic yield of visually-registered TB in comparison with conventional biopsy, and TB performed using other registration methods.


Tei index as a method of evaluating left ventricular diastolic dysfunction in acute myocardial infarction.
The Doppler index of overall left ventricular (LV) myocardial performance--the Tei index--has been shown to be a reliable indicator of all changes in LV systolic dysfunction, retaining an inverse relationship with the ejection fraction. The aim of this study was to examine the corresponding behaviour in relation to LV diastolic dysfunction in patients with acute myocardial infarction (AMI), a relationship that has not been studied previously. The study included 105 patients (77 men) with first AMI who were classified into four groups according to the severity of LV diastolic dysfunction: a) 25 patients with normal diastolic function (NDF), b) 36 with decreased peak filling rate pattern (DFR), c) 33 with impaired relaxation (IR) and d) 11 with pseudonormal or restrictive physiology (PN/RP). A complete echocardiographic study, including all conventional systolic and diastolic echo/Doppler parameters as well as measurement of the Tei index, was performed on the eighth post-infarction day (mean 8.07 +/- 0.96 days) in all patients. In the patients with IR (0.77 +/- 0.05) the index was significantly greater than in those of the NDF (0.55 +/- 0.03, p<0.01) or DFR (0.65 +/- 0.02, p<0.01) groups. The index in the DFR group was greater than in the NDF group, though not significantly so. In contrast, the index in the PN/RP patients (0.59 +/- 0.05) was significantly lower than in the patients with IR (p<0.01), whereas it did not differ from that of the patients in the NDF or DFR groups ("pseudonormalisation" of the index). The Tei index detects with reliability milder types of diastolic dysfunction. However, because of its "pseudonormalisation" in patients with PN/RP, the Tei index cannot be considered a reliable indicator of more severe patterns of LV diastolic dysfunction in AMI patients.


Chloroquine and hydroxychloroquine retinopathy-related risk factors in a Turkish cohort.
To evaluate the role of previously reported risk factors on developing retinopathy in patients treated with chloroquine (CQ) and hydroxychloroquine (HCQ). Ophthalmologic examination, visual field testing, and spectral domain-optical coherence tomography were performed in 31 patients treated with CQ and HCQ. Toxicity diagnosis was proven by electrophysiological assessment. The risk factors reported by the American Academy of the Ophthalmology (AAO) were compared between patients with (n = 5) and without toxicity (n = 26) findings. Risk score was calculated for each patient. CQ daily overdose per actual body weight was significantly higher in affected patients. There was no statistically significant difference between groups concerning risk score, estimated cumulative dose of CQ, daily dose of HCQ and CQ per lean body weight, daily overdose of CQ per lean body weight and actual body weight (>3 mg/kg). The cumulative dose of HCQ was significantly higher in non-affected patients. The risk factors reported by the AAO might not be applicable to all CQ- and HCQ-treated patients. Different risk factors not yet reported may play a role in the development of CQ and HCQ retinopathy.


Using eye height in different postures to scale the heights of objects.
Four experiments examined eye height (EH) scaling of object height across different postures. In Experiment 1, participants viewed rectangular targets while they were standing, seated, and prone. Standing and seated judgments were similar, possibly due to EH scaling. Prone judgments were significantly lower, a result not attributable to the unfamiliarity of that posture (Experiment 2). In Experiment 3, shifts of seated EH produced height overestimations equivalent to those of standing viewers. Experiment 4 examined the visual salience of size information in the seated and prone judgments by holding EH constant and manipulating another source: linear perspective. Participants viewed targets placed on true- and false-perspective (FP) gradients. The FP gradient affected prone judgments but not seated judgments, which presumably relied on EH. It appears that the human visual system weights size information differentially depending on its utility.


Tensile bond strength of three dual-cure bonding systems.
The purpose of this study was to test and compare the tensile bond strength of three dual-cure bonding systems on dentinal surfaces. Scotchbond MP Plus (3M Dental Products, St. Paul, MN 55144-1000), Allbond 2 (Bisco INC. Itasca, IL 60143) and Prime & Bond 2.1 Dual Cure (DENTSPLY Caulk, Milford, DE 19963-0359) were the three agents tested following manufacturer's instructions on flat dentinal surfaces. A total of 60 teeth were obtained, prepared and stored in distilled, deionized water prior to testing. Twenty teeth were distributed randomly to each bonding agent product. Ten of the 20 were light-cured and the other 10 were activated chemically, thereby creating six experimental groups. "Enforce" (DENTSPLY Caulk) resin cement was placed in a cylinder on the bonding agent interface in all 60 teeth. A pull test was performed using an Instron machine (Instron Corp., Canton, MA 02021) at a speed of 1 mm/min and under continuous load until failure. This study demonstrated that no significant difference existed among the means of the six sample groups involved when they were compared against each other using two-way ANOVA (p < 0.05). Yet, when comparing light-cured samples as a group, versus chemically-cured samples, light-cured samples produced a significantly stronger bond. When comparing adhesive systems, regardless of the cure method, Scotchbond MP Plus resulted in a significantly stronger bond than Allbond 2. When only comparing chemically-cured samples, Scotchbond MP Plus was significantly stronger than Allbond 2. Prime & Bond 2.1 was not significantly different than Scotchbond MP Plus or Allbond 2 regardless of cure type. No difference existed when comparing only light-cured samples. The bond strengths of adhesive systems are critical for the dentist in deciding which product to purchase to ensure the restoration will be a long-lasting one.


Acceleration effect of coupled oscillator systems.
We have developed a curved isochron clock (CIC) by modifying the radial isochron clock to provide a clean example of the acceleration (deceleration) effect. By analyzing a two-body system of coupled CICs, we determined that an unbalanced mutual interaction caused by curved isochron sets is the minimum mechanism needed for generating the acceleration (deceleration) effect in coupled oscillator systems. From this we can see that the Sakaguchi and Kuramoto (SK) model, which is a class of nonfrustrated mean field model, has an acceleration (deceleration) effect mechanism. To study frustrated coupled oscillator systems, we extended the SK model to two oscillator associative memory models, one with symmetric and the other with asymmetric dilution of coupling, which also have the minimum mechanism of the acceleration (deceleration) effect. We theoretically found that the Onsager reaction term (ORT), which is unique to frustrated systems, plays an important role in the acceleration (deceleration) effect. These two models are ideal for evaluating the effect of the ORT because, with the exception of the ORT, they have the same order parameter equations. We found that the two models have identical macroscopic properties, except for the acceleration effect caused by the ORT. By comparing the results of the two models, we can extract the effect of the ORT from only the rotation speeds of the oscillators.


Sexual behavior and experience of sexual coercion among secondary school students in three states in North Eastern Nigeria.
Interest in the reproductive health of adolescents continues to grow throughout the world. Few studies had explored the reproductive health knowledge, sexual behavior and experience of sexual coercion among secondary school students in North Eastern states of Nigeria. The objectives of this descriptive survey were to collect data to plan appropriate interventions that meet the reproductive health knowledge, service and skills needs of students in Bauchi, Borno and Gombe states. Face-to-face interviews were conducted for 624 consenting students who were randomly selected from eighteen secondary schools using an 83-item structured questionnaire. Data were collected on demographic profile, reproductive health knowledge, sexual behavior and experience of sexual coercion. The mean age of the respondents was 16.5 years. There were slightly more males (52%) than females (48%). Students' knowledge about reproductive health was generally low even though girls had better knowledge than boys. Thirteen percent of the entire students had had sexual experience; significantly more males (19%) than females (6%) had done so (p < 0.001). Among boys the age at sexual debut ranged from 10-26 with a mean of 15.7 and median of 16. By contrast, the age at first sex among girls ranged from 10 to 18 years with a mean and median of 16.1 and 17 years respectively. Only 24% of those who were sexually active used a condom during their last sexual encounter. Overall 11% of the students reported that they had been tricked into having sex, 9% had experienced unwanted touch of breast and backside, and 5% reported rape. Students low reproductive health knowledge and involvement in risky sexual activities predispose them to undesirable reproductive health outcomes.


Leukemia inhibitory factor tips the immune balance towards regulatory T cells in multiple sclerosis.
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS), for which current treatments are unable to prevent disease progression. Based on its neuroprotective and neuroregenerating properties, leukemia inhibitory factor (LIF), a member of the interleukin-6 (IL-6) cytokine family, is proposed as a novel candidate for MS therapy. However, its effect on the autoimmune response remains unclear. In this study, we determined how LIF modulates T cell responses that play a crucial role in the pathogenesis of MS. We demonstrate that expression of the LIF receptor was strongly increased on immune cells of MS patients. LIF treatment potently boosted the number of regulatory T cells (Tregs) in CD4(+) T cells isolated from healthy controls and MS patients with low serum levels of IL-6. Moreover, IL-6 signaling was reduced in the donors that responded to LIF treatment in vitro. Our data together with previous findings revealing that IL-6 inhibits Treg development, suggest an opposing function of LIF and IL-6. In a preclinical animal model of MS we shifted the LIF/IL-6 balance in favor of LIF by CNS-targeted overexpression. This increased the number of Tregs in the CNS during active autoimmune responses and reduced disease symptoms. In conclusion, our data show that LIF downregulates the autoimmune response by enhancing Treg numbers, providing further impetus for the use of LIF as a novel treatment for MS and other autoimmune diseases.


Patient Query in Adolescent Testicular Torsion Cases: "Was it Necessary to Mention My Scrotal Pain?"
Objective This study investigates the reasons for the failure to diagnose testicular torsion (TT) in different healthcare facilities (HCFs) and by various physicians. Method We retrospectively analyzed all male patients who underwent TT surgery within the adolescent age group between 2015 and 2023. Healthy adolescent patients who initially presented or were referred to an HCF and were subsequently diagnosed at our hospital for TT surgery were analyzed, focusing on why they were not diagnosed earlier. Results A total of 11 patients aged 10 to 17 who were surgically confirmed to have TT at our hospital between 2015 and 2023 were analyzed retrospectively. These patients had been admitted to various public and private HCFs due to the sudden onset of symptoms such as abdominal pain, vomiting, fainting, sweating, and walking difficulties during and after working hours. Four patients had previously been admitted to one HCF, while seven had been admitted two to six times to an HCF. All patients were healthy, and all but one had received age-appropriate education. However, only two of them had reported experiencing scrotal pain. Laboratory tests and/or radiological examinations were conducted on eight patients, and nine patients received medical treatment and/or prescriptions. None of the patients were initially diagnosed with acute scrotum. Conclusion Despite having unrestricted and free access to well-equipped HCFs, the early diagnosis and treatment of TT are not ensured. Factors contributing to this delay include patients' concealment of, or failure to fully disclose, scrotal complaints, as well as physicians' incomplete history taking and genital examinations. The physician's male gender was not found to contribute to an earlier diagnosis of TT. A mandatory genital examination should be included in the emergency assessment protocol for male patients.


Mediators of an Internet-based psychosocial intervention for women with breast cancer.
Many interventions have been designed to promote psychological adjustment in cancer survivors; however, notably few studies have specified the mediating processes through which these interventions work. The primary aim of this research is to examine theoretically and empirically grounded mediators of an Internet-based psychosocial intervention for women with breast cancer. Women (N = 88) diagnosed with breast cancer were randomly assigned to participate in a 3-hr workshop for creation of personal websites or a waitlist control. Mediating variables and dependent variables were assessed at baseline, 1 month, and 6 months following workshop participation. Indirect effects were tested using single and multiple mediator models. Relative to control participants, women randomized to Project Connect Online (PCO) evidenced statistically significant benefit 6 months after the workshop on depressive symptoms, positive mood, and life appreciation, as well as on hypothesized mediators (i.e., coping self-confidence, loneliness, social support from friends, but not emotional processing and expression). Change over 6 months in coping self-confidence, loneliness, and social support from friends mediated the relationship between the intervention and improvement in depressive symptoms. Coping self-confidence mediated the relationship between PCO and enhanced positive mood, and social support from friends mediated the relationship between PCO and increased life appreciation. Findings indicate how PCO promoted adaptive change and highlighted modifiable factors, including coping self-confidence, loneliness, and social support from friends, which contributed to positive adjustment to breast cancer. Additional potential mediators and ways in which the intervention can be enhanced are addressed.


Statistical Design of Experiment (DoE) based development and optimization of DB213 in situ thermosensitive gel for intranasal delivery.
DB213 is an HIV-1 replication inhibitor targeting the Central Nervous System for the treatment of HIV-associated neurocognitive disorders. Current study aims to develop an in situ thermosensitive gelling system for intranasal delivery of DB213 facilitated by Statistical Design of Experiment (DoE) to conduct a more efficient experimentation by extracting the maximum amount of information from limited experiments. In our current study, information was extracted from twenty-five experimental designs from MODDE® Software and a mathematical model was successfully developed to predict formulations to achieve desired performance as well as to analyze relationships between the amount of Pluronic F-127, Pluronic F-68, Chitosan, DB213 and the performances of in situ thermosensitive gels. Based on DoE, in situ thermosensitive gels of 1% DB213 (F1) and 5% DB213 (F2) were developed for further in vivo bioavailability and brain uptake evaluations in Sprague-Dawley rats and C57BL/6 mice, respectively. In comparison to DB213 water solution, intranasal administrations of F1 at 1 mg/kg in rats and F2 at 25 mg/kg in mice demonstrated relative bioavailabilities of 145% and 165% with significant increase in brain uptake.


Pimozide in the treatment of monosymptomatic hypochondriacal psychosis.
An account is given of six cases treated with pimozide. Four of there cases fall into the diagnostic category of monosymptomatic hypochondriacal psychosis, a group with a traditionally poor prognosis. Three out of the four have responded favourably to pimozide, while the fourth showed a partial improvement. A fifth case also showed a marked degree of improvement despite a possibility of early cerebral arteriopathy. The one case which showed no improvement was suspected all along of having a personality disorder rather than a psychotic illness, and this was subsequently confirmed. It is suggested that pimozide: a) may be an effective treatment for monosymptomatic hypochondriacal psychoses whatever their aetiology; and b) may differentiate rapidly between cases of monosymptomatic hypochondriacal psychoses and dysmorphophobias due to neurotically determined factors.


Size changes associated with metal adsorption onto modified bone gelatin beads.
Significant quantities of heavy metals will adsorb onto modified bone gelatin beads. As this adsorption occurs, the bead can undergo a substantial volume change. Research has shown that the equilibrium bead diameter was a function of the solution pH and the ion concentration in the solution. Here, we demonstrate that under certain conditions, the volume of the beads that absorbed the metal was only 35% of the bead volume when no metal was adsorbed. By taking advantages of these size changes, a fluidized-bed separator can be operated such that natural segregation of loaded beads occurs. This phenomenon may facilitate the design of continous separators for the recovery and concentration of heavy-metal-contaminated waters. These concepts are demonstrated using Cu(2+) adsorption onto such beads.


Soluble expression and purification of high-bioactivity recombinant human bone morphogenetic protein-2 by codon optimisation in Escherichia coli.
We developed a simple method of preparing recombinant human bone morphogenetic protein-2 (rhBMP-2) with high biological activity. This rhBMP-2 was overproduced in Escherichia coli as a fusion protein with thioredoxin 6xHis-tag at its amino terminus. The cDNA fragment of human bone morphogenetic protein-2 (hBMP-2) fused to the secretion signal of alkaline phosphatase (PhoA) was expressed under T7 promoter in E. coli. After DNA sequence confirmation, the recombinant vector pETpho-bmp2 was transformed into E. coli BL21 (DE3). rhBMP-2 was produced by the recombinant strain pETpho-bmp2/BL21 (DE3) in a soluble form with an yield of 6.2 mg/L culture. Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis (SDS-PAGE) results showed that the molecular weight of the product was approximately 28 kD. Moreover, rhBMP-2 was secreted as a dimer with a natural structure. rhBMP-2, purified by Ni Nitrilotriacetic acid Agarose (Ni-NTA) affinity chromatography, was used to examine osteosarcoma MG-63 cells and assay the alkaline phosphatase (ALP) activity. Results showed that rhBMP-2 induced MG-63 cell differentiation. When the final concentration was 500 ng/mL, the effect was more remarkable and ALP activity reached 525% compared with that of the control group.


Balloon dilatation of ureteral strictures.
Balloon catheter dilatation is now an accepted method for treating strictures of the upper urinary tract. A successful result was obtained in 34 (85%) of 40 patients with symptomatic stricture. The number of dilatations required for improved runoff from the kidney was one in 26 cases, two in six cases and three in one case. One patient had a permanent stent and six required a conventional operation. There were seven recurrences of stricture, all within 4 months after the dilatation. One of these patients required nephrectomy because of nonfunctioning kidney.