Acetamiprid resistance and fitness costs of melon aphid, Aphis gossypii: An age-stage, two-sex life table study.
The melon aphid, Aphis gossypii is a globally distributed crop pest with a wide host range. The intensive use of insecticides against this insect over several years has led to develop resistance against many insecticides including acetamiprid. Understanding the relationship between acetamiprid resistance and fitness of A. gossypii is essential to limit the spread of the resistant population in the field. In this study, age-stage, two-sex life table approach was used to investigate these relationships in the lab. Results showed that resistant strain (Ace-R) had a reduced fitness (relative fitness = 0.909) along with significantly decreased adult longevity, fecundity, net reproductive (R0), mean generation time (T) and gross reproductive rate (GRR). Compared to the susceptible strain (Ace-S), the pre-adult period and total pre-oviposition period (TPOP) were also significantly shorter in Ace-R strain. Moreover, the expression profiles of EcR, JHBP, JHAMT, JHEH, USP and Vg genes supposed to be involved in insect reproduction and development were analyzed using Quantitative Real Time PCR. The EcR, JHBP, JHAMT and USP genes were up-regulated, Vg gene was down-regulated while the mRNA level of JHEH gene was statistically same in the Ace-R strain compared to the Ace-S strain. Collectively, this study provides the occurrence and magnitude of fitness costs of A. gossypii against acetamiprid resistance and could be helpful to manage the resistance evolution in field populations.


Quantitative phytochemical profile, cholinesterase enzyme inhibition assay, antibacterial and antioxidant activities of Sarcococca saligna.
Aqueous methanol extracts of Sarcococca saligna leaves and roots were used in this work to explore its phytochemical contents, antioxidant, enzyme inhibition and antibacterial activities. Total phenolic contents were found to be in higher concentrations then total flavonoids contents in aqueous methanolic extracts of leaves. Antioxidant activity was performed using DPPH radical scavenging assay. In our findings both leaves and roots extracts were found to show substantial antioxidant potential. Aqueous methanolic extracts of both the leaves and roots gave significant inhibition against butyryl cholinesterase whereas against acetyl cholinesterase extracts of roots gave significant inhibition. The results were compared with the standard drug Eserine. The aqueous methanolic extract of leaves, roots and crude saponins isolated from leaf extracts gave moderate to significant antibacterial activity against the tested bacterial strains using agar disc diffusion method. According to the conclusions, S. saligna possesses significant antioxidant, enzyme inhibition, and antibacterial activities. Hence it is assumed that S. saligna has the potential to be used in the discovery and development of new bioactive compounds.


Rates and Predictors of Deterioration in a Trial of Internet-Delivered Cognitive Behavioral Therapy for Reducing Suicidal Thoughts.
It is necessary for suicide prevention interventions to demonstrate safety. One important aspect of safety is evidence that deterioration rates are low. No studies have examined deterioration of suicidal ideation in the context of an internet-based cognitive behavioral therapy (CBT) intervention to reduce suicidal ideation. A secondary analysis of the outcomes of an online trial was conducted to determine rates of deterioration in a CBT intervention called Living with Deadly Thoughts, relative to an attention control condition, and to identify factors associated with deterioration. The randomized controlled trial included 418 adults with suicidal ideation at baseline (77% females, mean age 40.6 years). Deterioration was defined in two ways: a reliable increase in Suicidal Ideation Attributes Scale (SIDAS score) of ≥6.0 units; or triggering the safety protocol during the trial as determined by high levels of suicidality. Analyses were repeated with multiply imputed data. Predictors of deterioration were identified using logistic regression analysis. 30 (14%) participants in the control group and 15 (7%) in the intervention group met criteria for reliable deterioration (Fisher's exact p = 0.027). In a fully adjusted logistic regression model, greater initial severity of suicidal thinking was associated with lower odds of deterioration, while intervention condition, demographics, psychological factors and mental health factors had no significant association with deterioration. Participation in an online suicide prevention intervention was associated with lower prevalence of reliable deterioration than participation in an attention-control intervention, providing further evidence that internet-based CBT interventions do not cause harm.HighlightsFirst study to assess deterioration in an internet suicide prevention interventionRates of reliable deterioration were higher in control (14%) than intervention (7%)No psychological or demographic factors were robustly associated with deteriorationFindings provide further evidence that internet based CBT programs are not harmful.


Association Between CD4 Count and Chemoradiation Therapy Outcomes Among Cervical Cancer Patients With HIV.
In Botswana, nearly two-thirds of cervical cancer patients are HIV-positive. This study examined the relationship between CD4 count and chemoradiation therapy outcomes among cervical cancer patients with HIV. A prospective cohort study of 231 HIV-positive women with locally invasive cervical cancer was conducted in Gaborone, Botswana from January 2015 to February 2018. Primary outcome was survival, defined as time from scheduled end of chemoradiation therapy to death or last contact with patient. Nadir CD4 count was defined as lowest CD4 available before cancer diagnosis. Delta CD4 count was defined as improvement from nadir CD4 to CD4 at cancer diagnosis. Hazard ratio (HR) analyses were adjusted for presenting variables (age, baseline hemoglobin, cancer stage, and performance status) and treatment variables (chemotherapy cycles and radiation dose). Two hundred thirty-one patients were included in nadir CD4 analysis; 139 were included in delta CD4 analysis. Higher delta CD4 was significantly associated with reduced mortality after adjusting for presenting and treatment variables (CD4 100-249: HR 0.45, 95% CI: 0.21 to 0.95; CD4 ≥250: HR 0.45, 95% CI: 0.20 to 1.02). Higher nadir CD4 showed a trend toward reduced mortality after adjusting for presenting and treatment variables (HR 0.94, 95% CI: 0.84 to 1.06). Higher delta CD4 (greater improvement from nadir CD4 to CD4 at cervical cancer diagnosis) is significantly associated with lower mortality. Although not statistically significant, data suggest that higher nadir CD4 may reduce mortality. These results reinforce the importance of early HIV diagnosis and antiretroviral therapy initiation, as their effects influence cervical cancer outcomes years later.


Effect of a new non-cleavable substrate analog on wild-type and serine mutants in the signature sequence of adenylosuccinate lyase of Bacillus subtilis and Homo sapiens.
Adenylosuccinate lyase (ASL) catalyzes two beta-elimination reactions in purine biosynthesis, leading to the question of whether the two substrates occupy the same or different active sites. Kinetic studies of Bacillus subtilis and human ASL with a new substrate analog, adenosine phosphonobutyric acid, 2'(3'), 5'-diphosphate (APBADP), show that it acts as a competitive inhibitor with respect to either substrate (K(I) approximately 0.1 microM), indicating that the two substrates occupy the same active site. Binding studies show that both the B. subtilis and human ASLs bind up to 4 mol of APBADP per mole of enzyme tetramer and that both enzymes exhibit cooperativity: negative for B. subtilis ASL and positive for human ASL. Mutant B. subtilis ASLs, with replacements for residues previously identified as critical for catalysis, bind the substrate analog similarly to wild-type ASL. Two serines in a flexible loop of ASL have been proposed to play roles in catalysis because they are close to the substrate in the crystal structure of Escherichia coli ASL. We have now mutated the corresponding serines to alanines in B. subtilis and human ASL to evaluate their involvement in enzyme function. Kinetic data reveal that human Ser(289) and B. subtilis Ser(262) and Ser(263) are essential for catalysis, while the ability of these Ser mutants to bind APBADP suggests that they do not contribute to substrate affinity. Although these serines are not visible in the crystal structure of human adenylosuccinate lyase complexed with substrate or products (PDB #2VD6), they may be interacting with the active sites.


Power in sports: A literature review on the application, assumptions, and terminology of mechanical power in sport research.
The quantification of mechanical power can provide valuable insight into athlete performance because it is the mechanical principle of the rate at which the athlete does work or transfers energy to complete a movement task. Estimates of power are usually limited by the capabilities of measurement systems, resulting in the use of simplified power models. This review provides a systematic overview of the studies on mechanical power in sports, discussing the application and estimation of mechanical power, the consequences of simplifications, and the terminology. The mechanical power balance consists of five parts, where joint power is equal to the sum of kinetic power, gravitational power, environmental power, and frictional power. Structuring literature based on these power components shows that simplifications in models are done on four levels, single vs multibody models, instantaneous power (IN) versus change in energy (EN), the dimensions of a model (1D, 2D, 3D), and neglecting parts of the mechanical power balance. Quantifying the consequences of simplification of power models has only been done for running, and shows differences ranging from 10% up to 250% compared to joint power models. Furthermore, inconsistency and imprecision were found in the determination of joint power, resulting from inverse dynamics methods, incorporation of translational joint powers, partitioning in negative and positive work, and power flow between segments. Most inconsistency in terminology was found in the definition and application of 'external' and 'internal' work and power. Sport research would benefit from structuring the research on mechanical power in sports and quantifying the result of simplifications in mechanical power estimations.


Development of a d-allose-6-phosphate derivative with anti-proliferative activity against a human leukemia MOLT-4F cell line.
d-Allose, a C-3 epimer of d-glucose, is a naturally occurring rare monosaccharide that shows anti-proliferative activity against several human cancer cell lines. However, d-allose requires a relatively high concentration for the activity to be observed. Thus, developing more potent derivatives is needed for application. In cells, d-allose is converted to d-allose-6-phosphate (A6P), which is responsible for the anti-proliferative activity of d-allose. In this study, we synthesized A6P derivative 1 with biodegradable protecting groups, which showed higher anti-proliferative activity than A6P against a MOLT-4F human leukemia cell line. Similarly protected derivative of d-glucose-6-phosphate (G6P) (2) and tetraacetyl-A6P (3) showed weaker and less activity compared with 1, respectively, suggesting that both A6P moiety and the protecting group on the phosphate group are responsible for the activity. In addition, significantly weaker induction of thioredoxin-interacting protein (TXNIP) expression by 1 compared with d-allose suggests that 1 exhibited cytotoxicity through the synergetic effect of inducing TXNIP expression and other mechanisms.


Clinical Presentation, Diagnosis and Prognosis of Pregnancy-Associated Breast Cancer.
Breast cancer in pregnancy is a rare entity generally presenting as a persistent breast mass, but is often a delayed finding due to the expected physiologic changes in the breast related to pregnancy and lactation. The preferred diagnostic workup of a persistent breast mass involves a combination of mammographic and ultrasonographic evaluation in addition to tissue diagnosis via core biopsy ; breast MRI is not recommended. Surgical excision should be reserved for definitive treatment in order to minimize fetal exposure to anesthesia. Evaluation for distant metastatic spread can be performed using radiographs and ultrasound to limit fetal radiation exposure . Similar to the non-pregnant patient, prognosis is primarily driven by tumor biology, however, there is limited and conflicting data regarding the impact of pregnancy on breast cancer outcomes with a distinct difference in survival among patients with breast cancer during pregnancy compared to those diagnosed postpartum.


Selective CO2 reduction to CH3OH over atomic dual-metal sites embedded in a metal-organic framework with high-energy radiation.
The efficient use of renewable X/γ-rays or accelerated electrons for chemical transformation of CO2 and water to fuels holds promise for a carbon-neutral economy; however, such processes are challenging to implement and require the assistance of catalysts capable of sensitizing secondary electron scattering and providing active metal sites to bind intermediates. Here we show atomic Cu-Ni dual-metal sites embedded in a metal-organic framework enable efficient and selective CH3OH production (~98%) over multiple irradiated cycles. The usage of practical electron-beam irradiation (200 keV; 40 kGy min-1) with a cost-effective hydroxyl radical scavenger promotes CH3OH production rate to 0.27 mmol g-1 min-1. Moreover, time-resolved experiments with calculations reveal the direct generation of CO2•‒ radical anions via aqueous electrons attachment occurred on nanosecond timescale, and cascade hydrogenation steps. Our study highlights a radiolytic route to produce CH3OH with CO2 feedstock and introduces a desirable atomic structure to improve performance.


Site-specific regulation of the GEF Cdc24p by the scaffold protein Far1p during yeast mating.
Receptor-mediated cell polarization via heterotrimeric G-proteins induces cytoskeletal rearrangements in a variety of organisms. In yeast, Far1p is required for orienting cell growth towards the mating partner by linking activated Gbetagamma to the guanine-nucleotide exchange factor (GEF) Cdc24p, which activates the Rho-type GTPase Cdc42p. Here we investigated the role of Far1p in the regulation of Cdc24p in vivo. Using time-lapse microscopy of mating cells and artificial membrane targeting of Far1p, we show that Far1p is necessary and sufficient to recruit Cdc24p to the plasma membrane. Wild-type Far1p contains a PH-like domain, which is required for its membrane localization in vivo. Interestingly, expression of membrane-targeted Far1p causes toxicity, most likely by activating Cdc42p uniformly at the cell cortex. The ability of full-length Far1p to function as an activator of Cdc24p in vivo requires its interaction with Cdc24p and Gbetagamma. Our results imply that Gbetagamma not only targets Far1p to the correct site but may also trigger a conformational change in Far1p that is required for its ability to activate Cdc24p in vivo.


From proinsulin-free insulin we obtained maximal purified insulin by means of preparative polyacrylamide electrophoresis (PADE). This substance appears in the analytical PADE as a uniform band and possesses glycine and phenylalanine as N-terminal amino acids. By use of the eviscerated rabbit as testing model, the product displays a higher hypoglycemic activity as compared with the Toronto standard.


Differential pulse polarographic assay of tolmetin sodium capsules.
Differential pulse polarography (DPP) is proposed as a direct method for the quantitation of tolmetin sodium in a capsule formulation (Tolectin--200 mg as the sodium dihydrate salt). Classical direct-current (DC) polarography has been employed to investigate the nature of the reduction occurring at the surface of the dropping mercury electrode (DME) using acetate buffer of pH 5.0 as the supporting electrolyte. The mean value of the results obtained by DPP expressed as a percentage of the stated amount, and the standard deviation, were found to be 99.87 +/- 0.43. The standard addition procedure used to assess the accuracy of the proposed method gave a mean percentage recovery of the total drug of 100.15 +/- 0.75%.


Synaptic acetylcholinesterase targeted by microRNA-212 functions as a tumor suppressor in non-small cell lung cancer.
Acetylcholinesterase expression is modulated in various types of tumor, which suggests it is associated with tumor development; however, the mechanism of acetylcholinesterase gene regulation in tumors remains unclear. Here, we report that acetylcholinesterase is aberrantly expressed in non-small cell lung cancer and is an evolutionarily conserved functional target of miR-212. Acetylcholinesterase expression was negatively regulated by miR-212 in vitro and was inversely correlated with miR-212 expression in vivo. In addition, acetylcholinesterase levels were increased, and miR-212 levels decreased, in non-small cell lung cancer cells during cisplatin-induced apoptosis. We further determined that acetylcholinesterase acted as a pro-apoptotic gene in non-small cell lung cells; and attenuated the growth of xenografts in nude mice when upregulated. In contrast, elevated miR-212 levels preserved the protective effect of acetylcholinesterase silencing by RNA interference against cisplatin-induced apoptosis, whereas restoration of miR-212-resistant synaptic acetylcholinesterase expression inhibited the miR-212 anti-apoptotic function. The results demonstrated that miR-212 exerted an anti-apoptotic effect through direct repression of synaptic acetylcholinesterase expression in non-small cell lung cancer cells. Taken together, our study revealed that synaptic acetylcholinesterase may be a tumor suppressor and is modulated by miR-212 in non-small cell lung cancer.


A novel endoribonuclease from the marine sponge Tethya aurantium specific to 2',5'-phosphodiester bonds.
In the marine sponge Tethya aurantium a novel endoribonuclease was found which specifically catalyzed the degradation of 2',5'-phosphodiester linkages and was therefore named endo-2',5'-ribonuclease. This enzymatic reaction yielded 2',3'-cyclic phosphate and 5'-OH products similarly to the 3'-5' bond cleavage in RNA, catalyzed by metal-independent ribonucleases. The partially purified enzyme preparation was used for its biochemical characterization. The enzyme did not require the presence of metal ions for its activity. The novel nuclease exhibited a preference for 5'-phosphorylated 2',5'-oligoadenylates, but 2'-5' linkage in 5'-triphosphorylated hetero-oligomers or homo-dimers comprising guanylate or uridylate residues instead of adenylate was cleaved as well. The enzyme was also able to catalyze the degradation of 5'-unphosphorylated 2',5'-oligoadenylates, except for 2',5'-diadenylate, which were weaker substrates for the enzyme than the respective 5'-triphosphorylated forms. The observed substrate specificity may refer to the specific role of the enzyme in the degradation of natural 2',5'-oligoadenylates (2-5A) that function in the interferon-induced mammalian 2-5A system as allosteric regulators of ribonuclease L. They are produced by 2-5A synthetases (OAS) that are also present in sponges, the most ancient phylum of Metazoa. We suggest that the newly discovered endoribonuclease found in the marine sponge T. aurantium could be a representative of the group of 2',5'-specific ribonucleases that primarily control the cellular levels of 2',5'-oligoadenylates.


Cigarette smoking, comorbidity, and general health among survivors of adolescent and young adult cancer.
We examined the associations between cigarette smoking, comorbidity, and general health among survivors of adolescent and young adult (AYA) cancer and a comparison group. From the 2012 to 2014 National Health Interview Surveys, we identified 1019 survivors of AYA cancer, defined as individuals who had been diagnosed with cancer between 15 and 39 years of age and were at least 5 years after their initial cancer diagnosis. A noncancer comparison group was matched on age, sex, and other factors. Self-reported smoking status (never smoker, former smoker, or current smoker), comorbidities (eg, asthma and diabetes), and general health status (excellent, very good, or good versus poor or fair) were compared among these groups. Survivors' smoking status before diagnosis and interaction with health care professionals regarding smoking cessation were reported. Multivariable logistic regressions modeled the associations between smoking status and comorbidity and general health. 33% of survivors were current smokers compared with 22% in the comparison group (P < .001). Prevalence of comorbidities and fair/poor health was significantly higher among survivors. Current smokers among survivors were more likely to report greater comorbidities (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.06-2.47; P = .03) and less likely to report at least good health (OR, 0.34; 95% CI, 0.22-0.54; P < .001) than never-smokers. Among survivors who smoked currently, 92% started smoking before diagnosis, and 37% reported having no smoking-related discussions with health care professionals in the previous year. Smoking among survivors of AYA cancer is associated with greater comorbidities and poorer general health. Younger survivors may need to be targeted for effective smoking cessation interventions. Addressing cigarette smoking during medical visits may encourage survivors to quit smoking. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2895-2905. © 2016 American Cancer Society.


Effect of prolonged walking with backpack loads on trunk muscle activity and fatigue in children.
This study investigated the effect of prolonged walking with load carriage on muscle activity and fatigue in children. Fifteen Chinese male children (age=6 years, height=120.0+/-5.4 cm, mass=22.9+/-2.6 kg) performed 20-min walking trials on treadmill (speed=1.1 ms(-1)) with different backpack loads (0%, 10%, 15% and 20% body weight). Electromyography (EMG) signals from upper trapezius (UT), lower trapezius (LT) and rectus abdominis (RA) were recorded at several time intervals (0, 5, 10, 15 and 20 min), and were normalized to the signals collected during maximum voluntary contraction. Integrated EMG signal (IEMG) was calculated to evaluate the muscle activity. Power spectral frequency analysis was applied to evaluate muscle fatigue by the shift of median power frequency (MPF). Results showed that a 15% body weight (BW) load significantly increased muscle activity at lower trapezius when the walking time reached 15 min. When a 20% BW load was being carried, increase in muscle activity was found from 5 min, and muscle fatigue was found from 15 min. In upper trapezius, increase of muscle activity was not found within the 20-min period, however, muscle fatigue was found from 10 min. No increased muscle activity or muscle fatigue was found in rectus abdominis. It is suggested that backpack loads for children should be restricted to no more than 15% body weight for walks of up to 20 min duration to avoid muscle fatigue.


Academic climate, well-being and academic performance in a university degree course.
The psychological climate within organisations affects not only the behaviour and the attitude of group members, but also the performance of the group itself. According to the ecological model, this research examines how learning in different classroom contexts of the same nursing degree programme can affect academic performance, well-being, self-esteem and perceived climate. Four scales were used to assess students' perceptions by collecting primary data while academic performance was measured by obtaining students' academic records. A questionnaire completed by 391 first-year nursing students was administered. Differences were observed in the perceptions of climate and academic performance in different classroom contexts with trends, which did not always overlap; however, strong correlations were observed among self-esteem, well-being and climate, and schoolmate relationships. Universities should not merely train competent professionals but also build learning communities that support the well-being of relationships and the development of well-being contexts. The findings support the need for an educational intervention for improving the quality of life and well-being of the community and individual students. This type of intervention requires a 'compliant' organisational environment that puts studetns, teachers and professionals in the condition to practice their professional skills.


Mechanism of salutary effects of finasteride on post-traumatic immune/inflammatory response: upregulation of estradiol synthesis.
The aim of this study was to evaluate whether pretreatment with finasteride, a 5alpha-reductase inhibitor, improves immune functions after trauma-hemorrhage. A number of studies have provided evidence for a gender dimorphism in host defense after trauma. Under stress conditions, such as trauma-hemorrhage, androgenic hormones have immunosuppressive effects, leading to increased susceptibility to sepsis, morbidity, and mortality. Testosterone is converted by 5alpha-reductase to 5alpha-dihydrotestosterone (DHT), a more potent androgen. Male C3H/HeN mice (8-10 weeks) were randomly assigned to receive finasteride or vehicle for 2 days and were then subjected to trauma-hemorrhage or sham operation. Trauma-hemorrhage was induced by a midline laparotomy and approximately 90 minutes of hemorrhagic shock (blood pressure, 35 mm Hg), followed by fluid resuscitation. Animals were killed 2 hours after resuscitation or sham procedure. Plasma levels and Kupffer cell production of cytokines (TNF-alpha, IL-6, IL-10, MCP-1, KC, and MIP-1alpha), lung neutrophil infiltration, and edema were evaluated. Finasteride administration prevented the increase in cytokine plasma levels, decreased DHT, and increased 17beta-estradiol plasma concentrations. In addition, neutrophil infiltration and edema formation in the lung were reduced by finasteride. The salutary effects of finasteride were abrogated after coadministration with an estrogen receptor inhibitor (ICI 182,780). Increased Kupffer cell cytokine production normally observed after trauma-hemorrhage was prevented by treatment with finasteride. These results suggest that inhibition of 5alpha-reductase leads to the conversion of testosterone to 17beta-estradiol, which produces salutary effects on the post-traumatic immune response.


Topical minoxidil for male pattern alopecia in two sets of twins.
Topical application of minoxidil has been reported to be effective in the treatment of androgenic alopecia. The treatment of two sets of identical twins is reported. One twin of each pair was treated with 3 percent topical minoxidil. The second twin was not treated for one year in one case and for five months in the other. The treated twin in each pair had more hair after treatment with minoxidil.


Single Nucleotide Polymorphisms Influence Histological Type and Grade of Canine Malignant Mammary Tumours.
Histological examination of canine mammary tumours is mandatory for determining the histological type and grade of the lesions, features that provide relevant information regarding the biological behaviour of the disease. Different histological classification systems and grading methods have been used to characterize canine mammary tumours. In this study, the relationship between the genetic profile of 87 female dogs (i.e. single nucleotide polymorphisms [SNPs] in genes known to be involved in mammary carcinogenesis) and the histological type and grade of malignant mammary tumours was assessed. The results demonstrated a significant relationship between genetic variation in genes RAD51, BRCA2, CHEK2, HER2, CDH1, COMT and PGR and these morphological features of the mammary lesions. Specifically, SNPs in RAD51 (rs23623251 and rs23642734), CHEK2 (rs397511718), HER2 (rs24537329) and PGR (rs8875007) were related to aggressive histotypes, with moderate to high histological grade. In contrast, SNPs in BRCA2 (rs23255542), HER2 (rs24537331), CDH1 (rs852280880 and rs850805755) and COMT (rs851328636, rs853133060 and rs85346495) were associated with tumour histotypes of good prognosis and of low histological grade. These data provide preliminary evidence for a genotypic-phenotypic correlation in canine mammary tumours, highlighting the mechanisms of their genesis, development and progression.


A novel targeted co-delivery nanosystem for enhanced ovarian cancer treatment via multidrug resistance reversion and mTOR-mediated signaling pathway.
Multidrug resistance (MDR) is the main challenge of successful chemotherapy for ovarian cancer patients, with 50% to 75% of ovarian cancer patients eventually relapsed due to it. One of the effective strategies for treating MDR and improving therapeutic efficiency of ovarian cancer is to use nanotechnology-based targeted drug delivery systems. In this study, a novel nano targeted co-delivery system modified by hyaluronic acid (HA) was developed by using gold nanorods coated with functionalized mesoporous silica nanoparticles (HA-PTX/let-7a-GNR@MSN) for combined delivery of hydrophobic chemotherapy drug Paclitaxel (PTX) and lethal-7a (let-7a), a microRNA (miR), to overcome MDR in ovarian cancer. Furthermore, we also analyzed the molecular mechanism of this nanotherapeutic system in the treatment of ovarian cancer. HA-modified nanocomplexes can specifically bind to the CD44 receptor, which is highly expressed in SKOV3/SKOV3TR cells, achieving effective cell uptake and 150% enhancement of tumor site permeability. The nanosystem realized the stable combination and protective transportation of PTX and miRs. Analysis of drug-resistant SKOV3TR cells and an SKOV3TR xenograft model in BALB/c-nude mice showed significant downregulation of P-glycoprotein in heterogeneous tumor sites, PTX release, and subsequent induction of apoptosis. More importantly, this nanosystem could synergistically inhibit the growth of ovarian tumors. Further studies suggest that mTOR-mediated signaling pathways play an important role in reversing drug resistance and inducing apoptosis. To sum up, these data provide a model for overcoming PTX resistance in ovarian cancer.


Microwave-assisted synthesis of BSA-protected small gold nanoclusters and their fluorescence-enhanced sensing of silver(I) ions.
A one-step microwave-assisted method is used for the synthesis of small gold nanoclusters, Au(16)NCs@BSA, which are used as a fluorescence enhanced sensor for detection of silver(I) ions with high selectivity and sensitivity.


Interaction of the opaque-2 gene with starch-forming mutant genes on the synthesis of zein in maize endosperm.
The combination of opaque-2 with starch-modified or starch-deficient mutants produced a cumulative and synergistic effect, respectively in regulating zein synthesis. The double mutant, brittle-2 opaque-2, which almost completely prevented the synthesis of Z1 and Z2, had high RNase activity. The possible involvement of RNase in effecting zein synthesis is discussed.


Long non-coding RNA MIAT is involved in the regulation of pyroptosis in diabetic cardiomyopathy via targeting miR-214-3p.
Diabetic cardiomyopathy (DCM) is one of the most common complications of diabetes without effective treatment options. Its pathogenesis is complex and remains unclear. Long non-coding RNA (lncRNA) MIAT allele has been reported to be enriched in DCM patients and activate a pyroptosis program in hypoxia-induced H9c2 cells. Thus, whether MIAT played a role in DCM pyroptosis remains to be clarified. In the study, the expression of MIAT was found elevated in the serum of diabetic patients, as well as in high-glucose induced cardiomyocytes and diabetic mice. Further, the expression levels of CASP1 and pyroptosis correlation factors (IL-1 and IL-18) were downregulated after silencing MIAT. Through modeling and validation experiments, we then confirmed that the MIAT-miR-214-3p-CASP1 axis serves as an essential point in pyroptosis of DCM mice. These results suggested that silencing MIAT would be a potential treatment strategy for DCM.


Are vaginal fluid concentrations of prolactin, alpha-fetoprotein and human placental lactogen useful for diagnosing ruptured membranes?
Vaginal fluid levels of prolactin (Prl), alpha-fetoprotein (AFP) and human placental lactogen (hPL) were assayed to investigate their usefulness in the diagnosis of ruptured membranes. Fifty-two patients at term were divided into those with intact membranes, and those with ruptured membranes. In patients with intact membranes the concentration of all three substances was low with few exceptions. The mean vaginal concentrations of the three proteins were significantly higher in patients with ruptured membranes, but low values were also found in this group. It is concluded, that because of the overlap between the values, Prl, AFP and hPL measurements in vaginal fluid do not represent a useful advance in the assessment of rupture of the membranes.


Effects of continuous subcutaneous insulin infusion on renal morphology in experimental diabetes. II. Glomerular basement membrane thickness.
Stereological studies were performed on renal glomeruli from control rats, untreated streptozotocin-diabetic rats and diabetics treated by subcutaneous infusion of insulin for 16 weeks. Estimates of glomerular basement membrane thickness were obtained by dividing membrane volume by membrane surface area. In addition, arithmetic and harmonic mean thicknesses were calculated from orthogonal intercept lengths, and used to provide information on the variability of basement membrane thickness. In untreated diabetics, both arithmetic and harmonic mean thicknesses were significantly greater than values found in control animals. The thickening of the basement membrane appeared to be generalized rather than markedly focal. All thickness variables were normalized by insulin infusion therapy. These findings underline the importance of good glycaemic control and early intervention in experimental diabetes and one of its main complications.


Molecular Twisting Affects the Solid-State Photochemical Reactions of Unsaturated Ketones and the Photomechanical Effects of Molecular Crystals.
Three groups of chalcone derivatives and their analogues involving halogen atoms (X=F, Cl, Br) have been synthesized. Firstly, the nearly planar acyclic chalcone derivatives were inclined to undergo photo-induced stereospecific [2+2] cycloaddition, which triggered the crystals to exhibit macroscopic motions of bending or cracking. In particular, the single-crystal-to-single-crystal transformation happened upon UV irradiation of the crystals, which was helpful for the understanding photomechanical effects. Cyclic 3,4-dihydronaphthalene-based chalcone analogues possess a more twisted conformation, and they tend to undergo trans-cis isomerization. No photomechanical effect was observed for the crystals of the cyclic chalcone analogues due to the lower isomerization rate. The twist degree of chroman-based molecules was in between of the first two, [2+2] cycloaddition and trans-cis isomerization simultaneously took place in crystals. Photo-induced bending and twisting were observed for the crystals of chroman-based chalcone analogues. Therefore, the differences in molecular dihedral angles in α,β-unsaturated ketones were responsible for their photochemical characters and in turn to tune the photomechanical effects. In this work, a bridge between the molecular structures and solid-state photochemical reactions triggered photomechanical crystals is built.


Low urinary oestrogen excretion during pregnancy, due to an impairment of fetal adrenocorticotrophic hormone secretion.
Four cases of newborn infants whose mothers had a low urinary oestrogen excretion during pregnancy are reported. Placental sulphatase deficiency in placental insufficiency were excluded by a dehydroepiandrosterone sulphate loading test. Postnatally, they developed a clinical picture characterized by an inappropriate secretion of cortisol which, by the results of an adrenocorticotrophic hormone stimulation test, appeared to be due to an impairment of adrenocorticotrophic hormone secretion. The prenatal and postnatal steroid metabolism is discussed.


Multiple folate transport systems in L1210 cells.
Biotin derivatives of methotrexate (biotin-SS-MTX) and folate (biotin-SS-folate), in which the functional components are joined by a dissociable disulfide-containing spacer, have been synthesized, purified by DEAE-Trisacryl chromatography, and characterized by HPLC, elemental analysis and mass spectrometry. These compounds provide a convenient means for the single-step purification of the folate transporters from L1210 cells. Parental L1210 murine leukemia cells, which contain only the microM transporter (the reduced folate/MTX transport protein) were treated with the N-hydroxysulfosuccinimide ester of biotin-SS-MTX, and a detergent extract of the plasma membranes was exposed to streptavidin-agarose beads to adsorb the labeled protein. Dithiothreitol cleavage of the disulfide linkage released the transporter, which migrated as a well-defined component (43 kDa) on SDS-PAGE gels; no other proteins were present. An L1210 subline (JF), obtained by adapting cells to grow on nanomolar concentrations of folate, contains both the microM transporter and the nM transporter (high-affinity folate binding protein). When these cells were treated with the N-hydroxysulfosuccimide ester of biotin-SS-folate and processed as described above, analysis on SDS-PAGE gels revealed the presence of two proteins, the microM transporter (43 kDa) and the nM transporter (39 kDa). Both transporters were characterized with respect to amino acid content; blocked N-termini precluded Edman sequencing. Treatment of the nM transporter with peptide:N-glycosidase F produced a smaller component (32 kDa); the microM transporter, conversely, was unchanged by this procedure. When the microM transporter in parental L1210 cells was labeled with fluorescein-MTX and then treated with phosphoinositol-specific phospholipase C (PI-PLC), no change in fluorescence was detected. Alternatively, when the nM transporter in the JF subline was labeled with fluorescein-folate and then treated with PI-PLC, complete loss of fluorescence was observed. These results indicate that the L1210 microM transporter is a non-glycosylated, integral membrane protein, while its nM counterpart is heavily glycosylated and anchored exofacially to the membrane by a glycosylphosphatidylinositol component.


Cancer Evolution and the Limits of Predictability in Precision Cancer Medicine.
The ability to predict the future behavior of an individual cancer is crucial for precision cancer medicine. The discovery of extensive intratumor heterogeneity and ongoing clonal adaptation in human tumors substantiated the notion of cancer as an evolutionary process. Random events are inherent in evolution and tumor spatial structures hinder the efficacy of selection, which is the only deterministic evolutionary force. This review outlines how the interaction of these stochastic and deterministic processes, which have been extensively studied in evolutionary biology, limits cancer predictability and develops evolutionary strategies to improve predictions. Understanding and advancing the cancer predictability horizon is crucial to improve precision medicine outcomes.


Shear stress induced release of von Willebrand factor and thrombospondin-1 in HUVEC extracellular matrix enhances breast tumour cell adhesion.
Endothelial cells in vivo are exposed to blood shear forces and flow perturbations induce their activation. Such modifications of hemodynamic can be observed in patients with cancer. We have submitted endothelial cells (HUVEC) to shear stress (13 dynes/cm(2)) and isolated their extracellular matrix (ECM) prior perfusion with breast adenocarcinoma cells (MDA-MB-231) in whole blood at a shear rate of 1500 s(-1). Exposure of HUVEC to 13 dynes/cm(2) (tau(13)) for 2 h enhanced the secretion of von Willebrand factor (vWF) and thrombospondin-1 (TSP-1) in the ECM. Moreover, MDA-MB-231 cell adhesion was enhanced to such treated-ECM. This over-adhesion was inhibited by pre-incubating the ECM with anti-vWF or anti-TSP-1 antibodies, or by blocking tumour cell alpha(v)beta(3) integrin. Although blood platelets were involved in tumour cell adhesion to ECM, blockade of platelet GPIb or alpha(IIb)beta(3) receptors did not specifically inhibit the enhanced tumour cell adhesion observed on tau(13). ECM. These findings indicate that shear stress can modulate the expression of adhesive proteins in ECM, which favours direct tumour cell adhesion via alpha(v)beta(3) and other receptors.


Quantitative analysis of penile ultrasonographic shape during the erectile cycle: a new diagnostic tool for erectile dysfunction? Repeatability of the method and preliminary results.
Penile modifications during erection interest not only penile length and circumference, but also its size and shape. In this investigation, the size and shape repeatability of a single standardized ultrasonographic image of penis during flaccidity and erection was quantified in a group of 19 patients complaining of erectile dysfunction. The penis of each patient was placed in the dorsal position and scanned by a 10 MHz linear ultrasonographic probe at the site of maximal corporeal size: (1) during flaccidity; (2) after an intracorporeal injection of 10 micrograms alprostadil; and (3) after a genital stimulation. Each scan was repeated three times for each patient and printed. On each print the outline of the tunica albuginea was drawn, digitized, and mathematically reconstructed by Fourier series that allow a separate quantification of the size and shape differences. Reliability of the tunica albuginea outline and repeatability of probe positioning were separately assessed within patient and functional phase, and found to be good. The actual examinations of two impotence patients performed using the described method are also given. The shape of the corpora cavernosa may be potentially indicative of the homogeneous function of the tunica albuginea, and it may be of use in patients' follow up.


MTTP-297H polymorphism reduced serum cholesterol but increased risk of non-alcoholic fatty liver disease-a cross-sectional study.
Microsomal triglyceride transfer protein (MTP) works to lipidate and assemble the apoB-containing lipoproteins in liver. It closely links up the hepatic secretion of lipid to regulate serum lipid and atherosclerosis. Cases of MTTP gene mutation is characterized by abetalipoproteinemia and remarkable hepatic steatosis or cirrhosis. Several MTTP polymorphisms have been reported relating to metabolic syndrome, hyperlipidemia and steatohepatitis. We supposed the regulation of serum lipids and risk of non-alcoholic fatty liver disease (NAFLD) formation may be modified by individual susceptibility related to the MTTP polymorphisms. A cross-sectional population of 1193 subjects, 1087 males and 106 females mean aged 45.9 ± 8.9 years, were enrolled without recognized secondary hyperlipidemia. Fasting serum lipid, insulin, and non-esterified fatty acid were assessed and transformed to insulin resistance index, HOMA-IR and Adipo-IR. After ruling out alcohol abuser, non-alcoholic fatty liver disease (NAFLD) was diagnosed by abdominal ultrasound. Five common MTTP polymorphisms (promoter -493 G/T, E98D, I128T, N166S, and Q297H) were conducted by TaqMan assay. Multivariate regression analysis was used to estimate their impact on serum lipid and NAFLD risk. Assessment revealed a differential impact on LDL-C and non-HDL-C, which were sequentially determined by the Q297H polymorphism, insulin resistance, body mass index and age. Carriers of homozygous minor allele (297 H) had significantly lower LDL-C and non-HDL-C but higher risk for NAFLD. Molecular modeling of the 297 H variant demonstrated higher free energy, potentially referring to an unstable structure and functional sequence. These results evidenced the MTTP polymorphisms could modulate the lipid homeostasis to determine the serum lipids and risk of NAFLD. The MTTP 297 H polymorphism interacted with age, insulin resistance and BMI to decrease serum apoB containing lipoproteins (LDL-C and non-HDL-C) but increase the risk of NAFLD formation.


Mechanistic study for drug induced cholestasis using batch-fabricated 3D spheroids developed by agarose-stamping method.
Cell spheroid culture can recapitulate the tissue microstructure and cellular responses in vivo. While there is a strong need to understand the modes of toxic action using the spheroid culture method, existing preparation techniques suffer from low efficiency and high cost. Herein, we developed a metal stamp containing hundreds of protrusions for batch bulk preparation of cell spheroids in each well of the culture plates. The agarose matrix imprinted by the stamp can form an array of hemispherical pits, which facilitated the fabrication of hundreds of uniformly sized rat hepatocyte spheroids in each well. Chlorpromazine (CPZ) was used as a model drug to investigate the mechanism for drug induced cholestasis (DIC) by agarose-stamping method. Hepatocyte spheroids showed a more sensitive detection of hepatotoxicity compared to 2D and Matrigel-based culture systems. Cell spheroids were also collected for staining of cholestatic protein and showed a CPZ-concentration-dependent decrease of bile acid efflux related proteins (BSEP and MRP2) and tight junction (ZO-1). In addition, the stamping system successfully delineated the DIC mechanism by CPZ that may be associated with the phosphorylation of MYPT1 and MLC2, two central proteins in the Rho-associated protein kinase pathway (ROCK), which were significantly attenuated by ROCK inhibitors. Our results demonstrated a large-scale fabrication of cell spheroids by the agarose-stamping method, with promising benefits for exploring the mechanisms for drug hepatotoxic responses.


Interactions between dietary fiber and ferulic acid change the aggregation of glutenin, gliadin and glutenin macropolymer in wheat flour system.
Glutenin macropolymer (GMP), glutenin and gliadin proteins are important indicators of the baking quality of dough. This study investigated the impacts of wheat bran and a mixture of ferulic acid (FA) and dietary fiber (DF) on the constitution of gluten proteins. Addition of wheat bran (100 and 150 g kg-1 ) into gluten decreased the gliadin/glutenin ratio, while the addition of different amounts of FA + DF (C1 group: 20 g kg-1 FA and 60 g kg-1 DF; C2 group: 30 g kg-1 FA and 90 g kg-1 DF) had the opposite effect. The GMP contents of wheat bran groups (B1 group: 100 g kg-1 ; B2 group: 150 g kg-1 ) were similar to that of the control group, and disulfide bond contents were increased. However, both GMP and disulfide bond contents of FA + DF groups significantly decreased. The GMP gel properties and microstructures were destroyed after addition of wheat bran and FA + DF. The wheat bran and FA + DF additives induced different effects on the thermal properties and secondary structures of glutenin, gliadin and GMP. The results suggest that the interaction mechanism of bran fractions and gluten proteins is not only related to the physicochemical properties of the additives, but also to interactions between the additives and the components of gluten protein. © 2020 Society of Chemical Industry.


Euler-Lagrange numerical simulation of improved magnetic drug delivery in a three-dimensional CT-based carotid artery bifurcation.
Magnetic drug targeting (MDT) is a promising method to improve the therapy efficiency for cardiovascular diseases (CVDs) and cancers. In MDT, therapeutic agents are bonded to superparamagnetic iron oxide nanoparticle (SPION) cores and then are guided toward the damaged tissue through a magnetic field. Fundamentally, it's vital to steer the SPIONs to the desired location to increase the capture efficiency at the target lesion. Hence, the present study aims to enhance the drug delivery to the desired branch in a carotid bifurcation. Besides, it is tried to decrement the particles' entry to the unwanted outlet by using four different magnet configurations (with a maximum magnetic flux density of 0.4 T) implanted adjacent to the artery wall. Also, the effect of particles' diameter -ranging from 200 nm to 2 µm- on the drug delivery performance is studied in the four cases. The Eulerian-Lagrangian approach with one-way coupling is employed for numerical simulation of the problem using the finite element method (FEM). The dominant forces acting on particles are drag and magnetophoretic. A computed tomography (CT) model of the carotid bifurcation is adopted to have a 3D realistic geometry. The blood flow is considered to be laminar, incompressible, pulsatile, and non-Newtonian. Boundary conditions are applied using the three-element Windkessel equation. Results are presented in terms of velocity, pressure, magnetic field flux density, wall shear stress, and streamlines. Also, the number of particles in each direction is presented for the four studied cases. The results show that using proper magnets configurations makes it possible to guide more particles to the desired branch (up to 4%) while preventing particles from entering the unwanted branch (up to 13%). By defining connectivity between oscillatory shear index (OSI) value and magnetic drug delivery efficacy, it becomes clear that places with lower OSI values are more proper to place the magnets than areas with higher OSI values. It was observed that increasing the diameter of particles does not necessarily result in a higher drug delivery efficiency. The configuration of the magnets and the size of particles are the main affecting parameters that should be chosen precisely to meet the most efficient drug delivery performance. Magnetic drug targeting (MDT) is a promising method to improve the therapy efficiency for cardiovascular diseases (CVDs) and cancers. Fundamentally, it's vital to steer the superparamagnetic iron oxide nanoparticles (SPIONs) to the target lesion location to increase the capture efficiency. Hence, the present study aims to enhance the drug delivery to the desired branch in a 3D carotid bifurcation. Besides, it is tried to decrement the particles' entry to the unwanted outlet by using four different magnet configurations implanted adjacent to the artery wall. The Eulerian-Lagrangian approach with one-way coupling is employed for numerical simulation of the problem using the finite element method (FEM). The dominant forces acting on particles are drag and magnetophoretic. The blood flow is laminar, incompressible, pulsatile, and non-Newtonian. The results show that it is possible to guide more particles to the desired branch (up to 4%) while preventing particles from entering the unwanted branch (up to 13%). By defining connectivity between oscillatory shear index (OSI) value and magnetic drug delivery efficacy, it becomes clear that places with lower OSI values are more proper to place the magnets than areas with higher OSI values.


Host defence against Staphylococcus aureus biofilms by polymorphonuclear neutrophils: oxygen radical production but not phagocytosis depends on opsonisation with immunoglobulin G.
Bacterial biofilms are increasingly recognised as a major cause of persistent infection and destructive inflammatory processes. In patients with biofilm infection, massive infiltration of leukocytes, particularly polymorphonuclear neutrophils is seen, and previous in vitro studies showed that PMN were able to phagocytose Staphylococcus aureus biofilms. We now addressed the question whether opsonisation of biofilms with immunoglobulin G and complement enhances the efficiency of phagocytosis, as it has been shown for "free-living" planktonic bacteria and other particulate materials. We found that incubation of biofilms with normal human serum resulted in IgG binding and in complement activation with deposits on the biofilm of C3bi. This "opsonisation", however, did not affect the adherence of PMN to the biofilms nor did it enhance degranulation or phagocytosis. The clearance of biofilms, however, was increased, and the oxygen radical production by the PMN depended critically on the coating of biofilms with IgG.


Charged groups at binding interfaces of the PsbO subunit of photosystem II: A combined bioinformatics and simulation study.
PsbO is an extrinsic subunit of photosystem II engaged in complex binding interactions within photosystem II. At the interface between PsbO, D1 and D2 subunits of photosystem II, a cluster of charged and polar groups of PsbO is part of an extended hydrogen-bond network thought to participate in proton transfer. The precise role of specific amino acid residues at this complex binding interface remains a key open question. Here, we address this question by carrying out extensive bioinformatics analyses and molecular dynamics simulations of PsbO proteins with mutations at the binding interface. We find that PsbO proteins from cyanobacteria vs. plants have specific preferences for the number and composition of charged amino acid residues that may ensure that PsbO proteins avoid aggregation and expose long unstructured loops for binding to photosystem II. A cluster of conserved charged groups with dynamic hydrogen bonds provides PsbO with structural plasticity at the binding interface with photosystem II.


Guanfacine and clonidine, alpha 2-agonists, improve paired associates learning, but not delayed matching to sample, in humans.
The present study compares the effects of two alpha 2-agonists, clonidine (0.5, 2, and 5 micrograms/kg, p.o.) and guanfacine (7 and 29 micrograms/kg, p.o.) in young healthy volunteers on their performance in visual paired associates learning (PAL) and delayed matching to sample (DMTS) visual short-term recognition memory tests. In the PAL test, clonidine 2 and guanfacine 29 micrograms/kg improved the subjects' performance. In the DMTS test, clonidine at 5 micrograms/kg delay-dependently impaired performance accuracy, and at 2 and 5 micrograms/kg it also slowed responses. Guanfacine had no effect on DMTS test performance. Clonidine 5 and guanfacine 29 micrograms/kg equally increased subjective feelings of sedation and reduced blood pressure. The results suggest that both clonidine and guanfacine facilitated PAL learning by improving "frontal strategies," but only clonidine disrupted "mneomonic processing" decreasing DMTS accuracy. The greater selectivity of guanfacine for alpha 2A-adrenoceptor subtype may explain the different profile of action of the drugs.


Salutary effects of androstenediol on hepatic function after trauma-hemorrhage are mediated via peroxisome proliferators-activated receptor gamma.
A recent study suggested that administration of androstenediol (Adiol) after trauma-hemorrhage (T-H) improves hepatic functions; however, the mechanism responsible for the salutary effect of Adiol remains unknown. Although studies indicate similarities and association between the anti-inflammatory properties of Adiol and peroxisome proliferator-activated receptor gamma (PPARgamma), whether the salutary effects of Adiol are mediated via upregulation of PPARgamma remains unclear. Male Sprague-Dawley rats underwent laparotomy and approximately 90 minutes of hemorrhagic shock (40 mm Hg), followed by resuscitation with 4 times the shed blood volume in the form of Ringer's lactate. Adiol (1 mg per kilogram of body weight, iv) was administered at the end of resuscitation. An additional group of rats were treated with PPARgamma antagonist (GW9662, 1 mg/kg ip) along with Adiol and the rats were sacrificed 5 hours thereafter. Hepatic functions were markedly depressed and plasma tumor necrosis factor-alpha, C-reactive protein and endothelin-1 were markedly increased after T-H. DNA-binding activity of nuclear factor kappa B and AP-1, and gene expressions of inducible nitric oxide synthase and endothelin-1 in the liver also increased significantly. These parameters were attenuated by Adiol treatment. These effects were accompanied an increased DNA-binding activity of PPARgamma in T-H-Adiol-treated rats. Treatment of rats with GW9662 prevented the salutary effects of Adiol after T-H. Since blockade of PPARgamma prevented the salutary effects of Adiol on hepatic functions and proinflammatory factors, this finding suggests that Adiol mediated its salutary effects after T-H via the PPARgamma-related pathways.


Endophthalmitis Caused by Corynebacterium Species: Clinical Features, Antibiotic Susceptibility, and Treatment Outcomes.
To report the clinical features, antibiotic susceptibility profiles, treatment, and visual acuity (VA) outcomes of endophthalmitis caused by Corynebacterium species. Retrospective case series. Patients with endophthalmitis caused by Corynebacterium species. Microbiology database records were retrospectively reviewed for all patients with endophthalmitis caused by Corynebacterium species from January 1, 1990 to December 31, 2012 at a large university referral center. The corresponding clinical records were then reviewed to evaluate the endophthalmitis clinical features and treatment outcomes. presenting clinical features, visual acuity outcomes, and antibiotic susceptibility patterns. Of 10 patients identified, clinical settings included post-cataract surgery (n = 6), post-penetrating keratoplasty (n = 2), and post-trabeculectomy (n = 2). The mean time from surgical procedure to presentation with endophthalmitis was 6.8 months (range: 1 day to 28 months). All isolates were vancomycin susceptible. Presenting VA ranged from 7/200 to no light perception. Initial treatment strategies were vitreous tap and intravitreal antibiotic injection (n = 5) and pars plana vitrectomy with intravitreal antibiotic injection (n = 5). VA outcomes were ≥ 20/60 in 5 (50%) of 10 patients and ≤ 20/400 in 5 (50%) of 10 patients. The most common clinical setting was post-cataract surgery. All isolates were susceptible to vancomycin. Despite prompt treatment with appropriate antibiotics, there were variable visual outcomes.


Self esteem and assertiveness of final year Turkish university students.
This study developed a quantitative methodology to ascertain the level of self esteem and assertiveness of last year students in baccalaureate degree programs at Cumhuriyet University Nursing School, School for Health Sciences' Midwifery School, Education Faculty's Mathematics Teacher, Classroom Teacher, and Social Sciences Teacher programs and to determine if there is a correlation between self esteem and assertiveness. The research population was a total of 372 students who were in their final year of university in these programs. Sampling was not done in the research, the entire population was studied. However there was a total of 82 students who were not included in the research because of illness, absenteeism, registration on hold, who could not be found on campus or who did not want to participate in the research and who did not correctly complete the survey form. The research was conducted with total of 290 students. Total response rate was 77.9%. The data were collected using a "Personal Information Form," Stanley Coopersmith Self Esteem Inventory (SEI) and Rathus Assertiveness Schedule (RAS). Frequency distribution, t test, correlation and variance analysis were used in the analysis of the data. The results of the study were that the nursing students had the highest scores from SEI (80.64+/-15.83). Similarly the nursing students had the highest scores on the RAS (36.29+/-25.33).


Roles of MET in human cancer.
The MET proto-oncogene was first identified in osteosarcoma cells exposed to carcinogens. Although expressed in many normal cells, MET is overexpressed in many human cancers. MET is involved in the initiation and development of various human cancers and mediates proliferation, migration and invasion. Accordingly, MET has been successfully used as a biomarker for diagnosis and prognosis, survival, post-operative recurrence, risk assessment and pathologic grading, as well as a therapeutic target. In addition, recent work indicates that inhibition of MET expression and function has potential clinical benefit. This review summarizes the role, mechanism, and clinical significance of MET in the formation and development of human cancer.


Nickel(II) carbonyl, ammonia, and aceto-nitrile complexes supported by a pyridine dipyrrolide pincer ligand.
The synthesis, isolation and crystal structures of nickel(II) carbonyl, aceto-nitrile and ammonia complexes supported by a dianionic, pyridine dipyrrolide pincer ligand [pyrr2py]2-, namely, carbonyl[2,2'-(pyridine-2,6-di-yl)bis-(3,5-di-p-tolyl-pyrrolido-κN)]-nickel(II), [Ni(C41H33N3)(CO)], ammine[2,2'-(pyridine-2,6-di-yl)bis-(3,5-di-p-tolyl-pyrrolido-κN)]nickel(II), [Ni(C41H33N3)(NH3)], and (aceto-nitrile-κN)[2,2'-(pyridine-2,6-di-yl)bis-(3,5-di-p-tolyl-pyrrolido-κN)]nickel(II), [Ni(C41H33N3)(CH3CN)], as well as the free ligand 2,6-bis-(3,5-di-p-tolyl-pyrrol-2-yl)pyridine, C41H35N3 or [pyrr2py]H2 are reported. The nickel complexes are four-coordinate and adopt a square-planar geometry. The CO stretch of the nickel-bound carbon monoxide ligand of [pyrr2py]Ni(CO) has been observed at 2101 cm-1. The ammonia and aceto-nitrile complexes, [pyrr2py]Ni(NH3) and [pyrr2py]Ni(NCMe) feature all-nitro-gen coordination spheres around nickel consisting of different N-donor ligand types.


Gastric secretory and humoral responses to anticipated feeding in five men.
It is believed that humans anticipate appetizing meals by increasing vagally mediated gastric acid secretion. Studies were conducted on 5 normal male volunteers to characterize further the secretory response to anticipated meals. Plasma gastrin and glucose levels were monitored to assess the possibility that these humoral factors participated in the observed secretory changes. Subjects were not fed for 22 hr and were intubated at 10 AM. Basal gastric collections were begun, and at 1 PM on different days, subjects either (a) selected meals of choice prepared in their presence for 1 hr before nasogastric tube withdrawal and meal ingestion or (b) were not food-teased or fed. Gastric collections were obtained every 10 min during the "test" hour (1-2 PM) during both (a) and (b) studies and titrated for gastric acid. Blood samples for plasma glucose and RIA gastrin were obtained during basal and test hours every 10 min. Pentagastrin-stimulated maximal acid output studies were conducted on all subjects on separate days. Results showed a progressive and statistically significant rise in gastric acid secretion when an appetizing, self-selected meal was anticipated. The magnitude of this rise was 55% of the mean pentagastrin-induced acid response. This acid response did not correlate with changes in plasma glucose or gastrin. The study demonstrated that pure psychic stimulation may be as effective an acid stimulant as sham feeding.


Renoprotection persists after cessation of treatment with very low doses of perindopril in Lyon hypertensive rats.
The possibility that angiotensin-converting enzyme inhibitors can protect hypertensive kidneys independently of any blood pressure (BP) decrease remains a matter of controversy. The present study investigates this theory in Lyon genetically-hypertensive (LH) rats. Male rats were used in the present study and were untreated (controls) or orally received 0.4, 0.1, 0.04, and 0.01 mg.kg(-1).d(-1) doses of perindopril from 3 to 17 weeks of age. At 16 and 23 weeks of age (ie during treatment and 6 weeks after its cessation), systolic BP (SBP) was measured by plethysmography, and urine was collected to measure the urinary protein (Uprot) and N-acetyl-seryl-aspartyl-lysyl-proline-to-creatinine (Cr) concentrations. The kidneys were dissected for a semiquantitative histological analysis. SBP was significantly lowered (-18%+/-2% and-11%+/-1% from controls at 16 and 23 weeks, respectively) with a 0.4 mg.kg(-1).d(-1) dose of perindopril. Lower doses did not affect SBP. Uprot/Cr decreased, and Ac-SDKP/Cr increased with all the doses of perindopril used. Uprot/Cr remained lower at 23 weeks in the rats treated with 0.1 mg.kg(-1).d(-1) and smaller doses. The ratio of Uprot/ Cr was closely (r=0.6) related to the histological lesions score. In LH rats, low doses of perindopril induce renoprotection which is independent of SBP decrease and persists after withdrawal of treatment.


Thromboelastographic distinction of malignant from benign breast masses: a preliminary report.
Thromboelastography is a newly applied tool for the detection of carcinoma. By comparing the thromboelastograph (TEG) of fresh whole blood (native) to that of blood to which celite has been added (celite activated), enhanced clotting is manifested which allows identification of individuals harboring carcinoma. Twenty women, obtained in a random sampling, entering the North Carolina Baptist Hospital for biopsy of breast masses were studied with routine clotting tests and TEGs preoperatively. TEG prediction of the biopsy result was correct in 16 of 20 patients (P less than 0.05). Thromboelastography may be a useful adjunct in screening for carcinoma in the evaluating persons with masses of unknown histology.


Data mining in predicting liver patients using classification model.
This study proposes to identify potential liver patients based on the results of a liver function test performed during a health screening to search for signs of liver disease. It is critical to detect a liver patient at an early stage in order to treat them effectively. A liver function test's level of specific enzymes and proteins in the blood is evaluated to determine if a patient has liver disease. According to a review of the literature, general practitioners (GPs) rarely investigate any anomalies in liver function tests to the level indicated by national standards. The authors have used data pre-processing in this work. The collection has 30691 records with 11 attributes. The classification model is utilized to construct an effective prediction system to aid general practitioners in identifying a liver patient using data mining. The collected results indicate that both the Naïve Bayes and C4.5 Decision Tree models give accurate predictions. However, given the C4.5 model offers more accurate predictions than the Naïve Bayes model, it can be assumed that the C4.5 model is superior for this research. Consequently, the liver patient prediction system will be developed using the rules given by the C4.5 Decision Tree model in order to predict the patient class. The training set, suggested data mining with a classification model achieved 99.36% accuracy and on the testing set, 98.40% accuracy. On the training set, the enhanced accuracy relative to the current system was 29.5, while on the test set, it was 28.73. In compared to state-of-the-art models, the proposed approach yields satisfactory outcomes. The proposed technique offers a variety of data visualization and user interface options, and this type of platform can be used as an early diagnosis tool for liver-related disorders in the healthcare sector. This study suggests a machine learning-based technique for predicting liver disease. The framework includes a user interface via which healthcare providers can enter patient information.


Modified TLR-mediated downregulation of miR-125b-5p enhances CD248 (endosialin)-induced metastasis and drug resistance in colorectal cancer cells.
CD248, also called endosialin or tumor endothelial marker-1, is markedly upregulated in almost all cancers, including colon cancers. Changes in microRNA profiles are one of the direct causes of cancer development and progression. In this study, we investigated whether a change in CD248 expression in colon cancer cells could induce drug resistance after chemotherapy, and we explored the relationship between miR-125b-5p levels and CD248 expression in Toll-like receptor (TLR)-modified chemoresistant colon cancer cells. TLR2/6 and TLR5 upregulation in drug-resistant colon cancer cells contributed to miR-125b-5p downregulation and specificity protein 1 (Sp1)-mediated CD248 upregulation via nuclear factor-kappa B (NF-κB) activation. Exposure to specific TLR2/6 or TLR5 ligands enhanced the expression of mesenchymal markers as well as the migratory activity of oxaliplatin- or 5-fluorouracil-resistant colon cancer cells. The transfection of a synthetic miR-125b-5p mimic into chemoresistant cells prevented Sp1 and CD248 activation and significantly impaired invasive activity. Furthermore, Sp1 or CD248 gene silencing as well as miR-125b-5p overexpression markedly reversed drug resistance and inhibited epithelial-mesenchymal transition in colon cancer cells. Taken together, these results suggest that changes in miR-125b-5p levels play an important role in Sp1-mediated CD248 expression and the development of drug resistance in TLR-mutated colon cancer cells.


Three Iodoargentate-Based Hybrids Decorated by Metal Complexes: Structures, Optical/Photoelectric Properties and Theoretical Studies.
So far, the development of new iodoargentate-based hybrids, especially those compounds with metal complex cations, and the understanding of their structure-activity relationships have been of vital importance but full of challenges. Herein, using the in-situ-generated metal complex cations as structural directing agents, three new iodoargentate-based hybrids, namely, [Co(phen)3]Ag2PbI6 (phen = 1,10-phenanthroline; 1), [Ni(5,5-dmpy)3]Ag7I9·CH3CN (5,5-dmpy = 5,5-dimethyl-2,2-bipyridine; 2) and [Co(5,5-dmpy)3]Ag5I8 (3), have been solvothermally prepared and then structurally characterized. Compound 1 represents one new heterometallic Ag-Pb-I compound characteristic of the chain-like [Ag2PbI6]n2n- anions. Compound 2 features the straight one-dimensional (1D) [Ag7I9]n2n- anionic moieties, while compound 3 contains infrequent two types of curved [Ag5I8]n3n- anions. Optical properties reveal that the title compounds exhibit interesting semiconductor behaviors with the band gaps of 1.59-2.78 eV, which endow them with good photoelectric switching performances under the alternate light irradiations. We also present their Hirshfeld surface analyses, and the theoretical studies (band structures, density of states (DOS) and partial density of states (PDOS)).


Patterns of resource allocation in male and female plants of Rumex acetosa and R. acetosella.
Patterns of resource allocation in the dioecious Rumex acetosa and R. acetosella were investigated. Males were found to allocate more to reproduction during flower production than females, whereas females invested considerably more in reproduction during seed production. Altogether, females allocated both a higher total amount and a higher proportion of energy to reproduction than did males. By regression analysis, the influence of plant size on reproductive effort was examined separately for males and females. The results indicated that while reproductive effort is sometimes lower for tall plants than for small plants, size-independent effects have a greater influence on reproductive effort than size distribution. An analysis of variance was conducted to investigate the effects of population, season, sex and their interactions on plant size, and an analysis of covariance was used to study differences in resource allocation patterns. Different interaction effects were found to be most important in the two species of Rumex.


Low glucose-enhanced TRAIL cytotoxicity is mediated through the ceramide-Akt-FLIP pathway.
To examine whether the tumor microenvironment alters cytokine-induced cytotoxicity, human prostate adenocarcinoma DU-145 cells were exposed to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and/or glucose deprivation, a common characteristic of the tumor microenvironment. TRAIL alone reduced cell survival in a dose-dependent manner. Glucose deprivation alone induced no cytotoxicity within 4 h. However, the combination of TRAIL (50 ng/ml) and glucose deprivation for 4 h increased cell death and PARP cleavage by promoting activation of caspase-8 and caspase-3, relative to that of TRAIL alone. Similar results were observed in human colorectal carcinoma CX-1 cells. Data from immunoblotting analysis reveal that glucose deprivation-enhanced TRAIL cytotoxicity is inversely related to the intracellular level of FLICE inhibitory protein (FLIP) but not that of death receptor 5 (DR5). Results from mass spectrometry show that glucose deprivation elevates ceramide. The elevation of ceramide may cause dephosphorylation of Akt and maintain dephosphorylation of Akt in the presence of TRAIL and then subsequently down-regulate the expression of FLIP. Taken together, the present studies suggest that glucose deprivation enhances TRAIL-induced cytotoxicity through the ceramide-Akt-FLIP pathway.


Venous Air Embolism Identified by 18F-Fluorocholine Dual-Phase PET/CT.
A 60-year-old woman with primary hyperparathyroidism with previous nonconclusive imaging studies was referred for 18F-fluorocholine (18F-FCH) PET/CT as part of the preoperative diagnostic imaging workup to localize the adenoma before minimally invasive surgery. 18F-FCH PET/CT with dual time point was performed, acquiring immediately and 60 minutes after 18F-FCH administration. The early images demonstrated possible hyperfunctioning parathyroid tissue in the mediastinum, located in the right upper paratracheal space (region 2R), with an incidental iatrogenic subclavian venous air bubble embolism presenting as high uptake in the early images that disappeared in the late images. No symptomatology was reported during the examination.


Physical Exercise as a Non-Pharmacological Intervention for Attenuating Obesity-Related Complications in Children and Adolescents.
Obesity is the most prevalent nutrition-related disorder among the pediatric population [...].


Strategies for treatment of dystonia.
Treatment of dystonias is generally symptomatic. To produce sufficient therapy effects, therefore, frequently a multimodal and interdisciplinary therapeutic approach becomes necessary, combining botulinum toxin therapy, deep brain stimulation, oral antidystonic drugs, adjuvant drugs and rehabilitation therapy including physiotherapy, occupational therapy, re-training, speech therapy, psychotherapy and sociotherapy. This review presents the recommendations of the IAB-Interdisciplinary Working Group for Movement Disorders Special Task Force on Interdisciplinary Treatment of Dystonia. It reviews the different therapeutic modalities and outlines a strategy to adapt them to the dystonia localisation and severity of the individual patient. Hints to emerging and future therapies will be given.


mTOR Signaling and SREBP Activity Increase FADS2 Expression and Can Activate Sapienate Biosynthesis.
Cancer cells display an increased plasticity in their lipid metabolism, which includes the conversion of palmitate to sapienate via the enzyme fatty acid desaturase 2 (FADS2). We find that FADS2 expression correlates with mammalian target of rapamycin (mTOR) signaling and sterol regulatory element-binding protein 1 (SREBP-1) activity across multiple cancer types and is prognostic in some cancer types. Accordingly, activating mTOR signaling by deleting tuberous sclerosis complex 2 (Tsc2) or overexpression of SREBP-1/2 is sufficient to increase FADS2 mRNA expression and sapienate metabolism in mouse embryonic fibroblasts (MEFs) and U87 glioblastoma cells, respectively. Conversely, inhibiting mTOR signaling decreases FADS2 expression and sapienate biosynthesis in MEFs with Tsc2 deletion, HUH7 hepatocellular carcinoma cells, and orthotopic HUH7 liver xenografts. In conclusion, we show that mTOR signaling and SREBP activity are sufficient to activate sapienate metabolism by increasing FADS2 expression. Consequently, targeting mTOR signaling can reduce sapienate metabolism in vivo.


Effects of chlorinated phenols on immunity in rats.
Female Sprague - Dawley rats were exposed to 0, 5, 50 or 500 ppm 2-chlorophenol (2-CP) or pentachlorophenol (PCP) from weaning to 3 weeks postparturition after breeding at 90 days of age. Progeny were weaned at 3 weeks of age and continued on chlorophenol treatment for 10 weeks at which time major immune functions were tested. Humoral immunity was measured by an indirect ELISA, cell-mediated immunity was monitored by delayed-type hypersensitivity (DTH) to oxazolone, and macrophage function was tested by phagocytosis of sheep red blood cells. Rats treated with cyclophosphamide were included as a positive immunosuppressed control. PCP-treated rats had significantly decreased antibody titers and DTH response and increased induced peritoneal macrophage numbers which displayed hyperphagocytic activity. Immune responses in rats treated with 2-CP were not significantly different from controls. The data indicate that (1) the immune system may be a sensitive target for PCP toxicity but not for 2-CP, (2) closely related chlorophenolic chemical isomers may exert different toxic effects on the immune system, and (3) PCP can exert depressive effects on some major immune parameters while enhancing others.


Design and microwave absorption properties of thistle-like CoNi enveloped in dielectric Ag decorated graphene composites.
A novel hierarchical composites for coupling thistle-like CoNi with dielectric Ag decorated graphene in paraffin wax as high performance microwave absorber has been synthesized by a facile two-step strategy. The components, particle size, microstructure and morphology of the resulting composites are characterized by X-ray diffraction, X-ray photoelectron spectroscopy, Raman spectra, scanning electron microscope, transmission electron microscopy and energy dispersive X-ray spectroscopy, etc. Due to the unique flower structure and good synergistic effect of dielectric loss and magnetic loss, thistle-like CoNi@dielectric Ag decorated graphene composites have showed glorious microwave absorption intensity and frequency width. The maximum reflection loss of -61.9 dB can be gained at 6.96 GHz, which has rarely been reported yet. In addition, the corresponding effective bandwidth with reflection loss less than -10 dB is 5.6 GHz ranging from 12.4 to 18 GHz at only 1.67 mm thickness. This highly efficient and broad band features endow thistle-like CoNi@dielectric Ag decorated graphene composites with promising applications in microwave absorption, electromagnetic shielding, information safety, direct broadcast satellite and military radar fields.


Inactivation of trypsin inhibitors in sweet potato and taro tubers during processing.
In order to understand the extent of elimination of trypsin inhibitors during processing of sweet potato (Ipomoea batatas) and taro (Colocasia esculenta) tubers, a detailed study was conducted using tubers processed by oven drying, cooking, and microwave baking. Between 80 and 90% trypsin inhibitor (TI) activity was retained in sweet potato chips up to 2h at 70 degrees C. Among the four cultivars of sweet potatoes, RS-III-2 trypsin inhibitors were more heat labile. Heating at 100 degrees C led to rapid inactivation of TI of sweet potatoes. Varietal differences in thermal stability were more pronounced for the trypsin inhibitors of taro than sweet potatoes. Taro inhibitors were also more rapidly inactivated than sweet potato TI. Between 17 and 31% TI activity was retained in cooked tuber pieces of sweet potatoes, while only 3-10% were retained in taro cultivars. Very effective inactivation of trypsin inhibitors of sweet potatoes and taro could be obtained through microwave baking. Flour prepared from taro was devoid of TI activity, while 5-12% TI activity was retained in the flour prepared from sweet potatoes. The study clearly established that among the four techniques used, microwave baking and flour preparation were the best methods to eliminate TI from sweet potatoes and taro.


Fetal anesthesia and pain management for intrauterine therapy.
Anesthesia provision for fetal intervention differs from most other anesthetic situations insofar as anesthesiologists must care for 2 or more patients-each with potentially conflicting requirements. The first is the mother who can readily indicate discomforts, can be monitored directly, and to whom drugs may be administered directly and easily. For the fetus (or fetuses), nociception must be assumed or inferred indirectly, monitoring is limited at best, and drug administration is complicated and often indirect. Fetal and maternal hemodynamic stability must be assured; and a plan to resuscitate the fetus, should problems occur during the procedure, must be developed.


Balance control in unstable sitting in individuals with an acute episode of low back pain.
Low back pain (LBP) is associated with altered postural control, mostly observed at later stages in the LBP trajectory. It is unclear whether postural control differs in the acute phase of LBP. Is postural control different in the acute phase of LBP (<2 weeks) and do differences depend on pain intensity, psychological features and/or availability of vision to control posture? Cross-sectional study design. An unstable sitting paradigm (to reduce the contribution of the legs) assessed postural control of participants with acute LBP (n = 133) and pain-free controls (n = 74). Centre of pressure (CoP) reflected seat movements. Participants balanced with eyes closed, open, or with visual feedback of the anteroposterior CoP position. Balance performance was expressed by CoP displacement and velocity, and stabilogram diffusion analysis. Generalised estimating equations (GEEs) including body mass index, sex, and safety bar touch, tested differences between groups and between balance conditions. Separate GEEs were used to model performance measures and bar touch (yes/no) including pain intensity, disability and psychological features. CoP displacement and critical point coordinates (time and distance where CoP diffusion rate or spread slows) were larger in LBP than pain-free controls independent of balance condition. Long-term diffusion rate was greater in LBP than controls with eyes closed. CoP velocity measures (RMS, short term diffusion rate) were not different between groups. Pain intensity and psychological features were not linearly related to balance performance in participants with acute LBP. Higher pain catastrophizing was associated with touching the safety bar. Postural control differs in acute LBP than pain-free controls. Findings might be explained by altered sensory processing, lesser ability to reweight proprioceptive information and/or less accurate trunk muscle control. Although not linearly related to pain-intensity or psychological features in the acute stage, reduced balance performance could potentially have impact on LBP recovery.


Plant population heterogeneity and pathogen and herbivore levels: a field experiment.
The identity of neighbouring plants in a population is thought to affect the disease levels of an individual plant: disease levels are expected to be higher for susceptible plants surrounded by other susceptible plants as compared to susceptible plants that have resistant plants as neighbours. To explore this idea, plants in a natural population of the annual sunflower, Helianthus annuus, were scored in 1988 for levels of the rust pathogen Puccinia helianthi. Progeny of plants with high rust levels (families predicted to be susceptible to the disease) were grown in 1989 in a series of field plots at either high frequency (all plants in a plot of one family) or in low frequency (a plot with plants of many families). There was a positive correlation between rust levels of the parent plants in 1988 and their progeny in 1989, but the frequency of a family in the experimental plots did not affect rust levels. Generally low rust levels at the site, as well as other factors, probably contributed to the absence of a frequency effect. Herbivore levels and plant survival and reproduction varied among plots, but were not affected by the plot composition.


Wormlike micelles and microemulsions in aqueous mixtures of sucrose esters and nonionic cosurfactants.
A study of the phase and rheological behavior of sucrose hexadecanoate (C16SE)/cosurfactant/water systems in the presence of solubilized oil, using complementary techniques such as dynamic light scattering and small angle X-ray scattering, is presented. Viscoelastic wormlike micellar solutions are found when a nonionic lipophilic cosurfactant is added to C16SE aqueous systems. Contrary to previous reports, the effect of oil solubilization on these wormlike micelles is not unique and depends on several factors. Linear alkyl chain oils that tend to solubilize in the micellar core have a disrupting effect, decreasing the relaxation time and the viscosity of the systems. This effect is larger as the molecular volume of oil increases and as the solubility of the cosurfactant in oil increases. On the other hand, oils that penetrate in the palisade layer, such as p-xylene, induce micellar growth and have a thickening effect at a given micellar composition. Thermodynamic considerations are used to explain the experimental results.


Comparative evaluation of immunohistochemistry and real-time PCR for measuring proinflammatory cytokines gene expression in livers of rats treated with gold nanoparticles.
Gold nanoparticles (GNPs) possess promising applications in targeted drug delivery and controlled release of a variety of chemical agents. However, the immunocompatibility of GNPs is poorly understood. After exposure, GNPs preferentially tend to accumulate is liver, where they induce an acute phase proinflammatory response. We therefore compared the two techniques, immunohistochemistry and real-time PCR for measuring the protein and mRNA expressions of IL-1β, IL-6 and TNF-α in liver of rats after intraperitoneal injections (5μg/animal) of 10 and 50nm diameter GNPs for 1 and 5days. The results showed that both 10nm and 50nm GNPs induced an acute phase expression of proinflammatory cytokines that receded on day 5. The proinflammatory response on day 1 was comparatively more severe with 50nm GNPs than 10nm GNPs. A comparative evaluation between immunostaining and real-time PCR showed that the latter technique is more sensitive as it could detect the cytokines mRNA expression in control samples as well. This could be partly attributed to the amplification strategy used in real-time PCR and partly to the variations in the half lives of cytokines mRNA and their resulting proteins.


Transcriptional and post-transcriptional gene regulation of HTLV-1.
Adult T-cell leukemia (ATL) is an aggressive hematologic malignancy caused by human T-cell leukemia virus type I (HTLV-1). Tax, encoded by the HTLV-1 pX region, has been recognized by its pleiotropic actions to play a critical role in leukemogenesis. Three highly conserved 21-bp repeat elements located within the long terminal repeat, commonly referred to as Tax-responsive element 1 (TRE-1), are critical to Tax-mediated viral transcriptional activation through complex interaction with cyclic AMP-responsive element binding protein (CREB), CBP/p300 and PCAF. Tax has also been shown to activate transcription from a number of critical cellular genes through the NF-kappaB and serum-responsive factor pathways. Tax transactivation has been attributed to the protein's interaction with transcription factors, chromatin remodeling complexes, cell cycle and repair genes. In this review, we will discuss some of the latest findings on this fascinating viral activator and highlight its regulation of cellular factors including CREB, p300/CBP and their effect on RNA polymerase II and chromatin remodeling, as well as its role in cytoplasmic and nuclear function. We will highlight the possible contribution of each factor, discuss Tax's critical peptide domains and highlight its post-transcriptional modifications. It is quite obvious that, collectively, Tax's effects on a wide variety of cellular targets cooperate in promoting cell proliferation and leukemogenesis. In addition, the post-transcriptional effects of Rex play an important role in virus replication. Understanding these interactions at a molecular level will facilitate the targeted development of drugs to effectively inhibit or treat ATL.


Cystectomy and ileal conduit for neurogenic bladder: Comparison of the open, laparoscopic and robotic approaches.
The objective of the present study was to compare the outcomes of open versus laparoscopic versus robotic cystectomy and ileal conduit for neurogenic lower urinary tract dysfunction (NLUTD). The charts of all patients who underwent cystectomy and ileal conduit for NLUTD between January 2004 and November 2020 in an academic center were retrospectively reviewed. The approach was either open, laparoscopic or robot-assisted depending on the period (i.e., three consecutive era). For the robotic approach, the diversion was done either intracorporeally or extracorporeally. We compared the perioperative and late postoperative outcomes between the three groups. After exclusion of 10 patients with non-neurogenic benign conditions, 126 patients were included over the study period. The most frequent neurological conditions were multiple sclerosis (36.5%) and spinal cord injury (25.4%). The approach was open, laparoscopic or robot-assisted in 31 (24.6%), 26 (20.6%) and 69 (54.7%) cases respectively. Seventy-two patients experienced a 90-day postoperative complication (57.1%) of which 22 had a major complication (Clavien 3 or higher, 17.5%) including one death (0.8%). The rate of major postoperative complications was significantly lower in the robotic group (23% vs. 23% vs. 10%; p = 0.049) while the rate of overall complications was comparable across the three groups (58.1% vs. 53.9% vs. 60.6%; p = 0.84). After a median follow-up of 23 months, 22 patients presented a late complication (17.6%), mainly incisional hernia (5; 4%) and uretero-ileal stricture (9; 7.2%). The rate of late complications did not differ significantly between the three approaches. Cystectomy and ileal conduit for neurogenic bladder is associated with a relatively high perioperative morbidity. The robot-assisted approach may decrease the risk of major postoperative complications.


Measurement of plasma placental proteins and estriol in the detection of intrauterine growth retardation.
This study was designed as an assessment of the clinical value of total estriol, placental lactogen (hPL), pregnancy specific glycoprotein (SP1), pregnancy-associated plasma protein-A (PAPP-A) and placental protein 5 (PP5), measured in a single sample of maternal serum, in the detection of intrauterine growth retardation (IUGR) in a large series of high risk pregnancies. Our results show the highest detection rate with SP1 (51%) and second highest with hPL (35%); estriol was less useful while PAPP-A and PP5 were of no value. However, there was 31% of false positives with SP1 compared with 14% for hPL. The best combination of the five parameters for the diagnosis of IUGR was achieved by measurement of both SP1 and hPL, with a low concentration of either protein indicating IUGR (sensitivity 63%, specificity 63%).


Survivability and reactivity of glycine and alanine in early oceans: effects of meteorite impacts.
Prebiotic oceans might have contained abundant amino acids, and were subjected to meteorite impacts, especially during the late heavy bombardment. It is so far unknown how meteorite impacts affected amino acids in the early oceans. Impact experiments were performed under the conditions where glycine was synthesized from carbon, ammonia, and water, using aqueous solutions containing (13)C-labeled glycine and alanine. Selected amino acids and amines in samples were analyzed with liquid chromatography-mass spectrometry (LC/MS). In particular, the (13)C-labeled reaction products were analyzed to distinguish between run products and contaminants. The results revealed that both amino acids survived partially in the early ocean through meteorite impacts, that part of glycine changed into alanine, and that large amounts of methylamine and ethylamine were formed. Fast decarboxylation was confirmed to occur during such impact processes. Furthermore, the formation of n-butylamine, detected only in the samples recovered from the solutions with additional nitrogen and carbon sources of ammonia and benzene, suggests that chemical reactions to form new biomolecules can proceed through marine impacts. Methylamine and ethylamine from glycine and alanine increased considerably in the presence of hematite rather than olivine under similar impact conditions. These results also suggest that amino acids present in early oceans can contribute further to impact-induced reactions, implying that impact energy plays a potential role in the prebiotic formation of various biomolecules, although the reactions are complicated and depend upon the chemical environments as well.


Behavioral response inhibition and maturation of goal representation in prefrontal cortex after puberty.
Executive functions including behavioral response inhibition mature after puberty, in tandem with structural changes in the prefrontal cortex. Little is known about how activity of prefrontal neurons relates to this profound cognitive development. To examine this, we tracked neuronal responses of the prefrontal cortex in monkeys as they transitioned from puberty into adulthood and compared activity at different developmental stages. Performance of the antisaccade task greatly improved in this period. Among neural mechanisms that could facilitate it, reduction of stimulus-driven activity, increased saccadic activity, or enhanced representation of the opposing goal location, only the latter was evident in adulthood. Greatly accentuated in adults, this neural correlate of vector inversion may be a prerequisite to the formation of a motor plan to look away from the stimulus. Our results suggest that the prefrontal mechanisms that underlie mature performance on the antisaccade task are more strongly associated with forming an alternative plan of action than with suppressing the neural impact of the prepotent stimulus.


On the scope of presupposition in discourse reading comprehension.
referential relationships can be communicated through presupposition. The presupposition trigger (also) in Jiayan also bought eggs exerts a pragmatic constraint that besides the object, the verb constrains additional and alternative referents. Our study provided a novel set of evidence that the reader preferred larger- over smaller-sized sets for the scope of presupposition in discourse comprehension. The structural hierarchy in smaller-sized sets and the earlier-mentioned structural details in larger-sized sets drove higher preference. Furthermore, readers' difference in their preference reflected their tendency to attend to discourse structural information. These findings are consistent with the multiple constraints hypothesis/the presupposition maximization principle hypothesis, rather than the local bias hypothesis. The present study enlightened the understanding of structural constraints on processing the number and the identity of presupposed referential information in discourse reading comprehension.


Neonatal Lupus presenting with neonatal hemochromatosis-like liver disease that responded to steroids: a case report.
Neonatal lupus erythematosus is a rare multisystem autoimmune disorder that predominantly involves the heart with congenital heart block but can involve other organs including the liver. The disease results from passage of maternal autoantibodies to the fetus and manifests in various forms depending on the organ involved. Neonatal lupus liver disease manifestations range from benign elevation in aminotransferases to fatal hepatic insufficiency with iron deposition that does not respond to therapy. Only a handful of cases have been reported to date. The antibodies implicated are Sjogren Syndrome types A and B antibodies. Other non-specific autoantibodies can be positive as well such as antinuclear antibodies. Smooth muscle antibodies are classically considered specific to autoimmune hepatitis, and while they have been described in other chronic liver diseases, they have not been described in neonatal lupus liver disease. Herein we report a rare case of neonatal cholestasis due to neonatal lupus liver disease that presented with a positive smooth muscle antibodies in addition to a biochemical picture of neonatal hemochromatosis, with a remarkably elevated ferritin, that responded well to steroid therapy. An 8-day old full-term baby girl was referred to our center for evaluation of neonatal bradycardia and generalized jaundice that started in the first day of life. Prenatal history was significant for fetal bradycardia. Examination was unremarkable except for bradycardia and generalized jaundice. Laboratory findings included elevated alanine aminotransferase, aspartate aminotransferase, Alkaline Phosphatase, and total and direct bilirubin. Her ferritin was markedly elevated along with triglycerides. Sjogren syndrome antibodies were positive in addition to antinuclear and anti-smooth muscle antibodies. The diagnosis of cardiac neonatal lupus was given, and her liver disease was attributed to lupus despite the biochemical picture of neonatal hemochromatosis. She was started on oral prednisolone for which her liver function parameters showed a dramatic response and continued to be within the normal limits several weeks after discontinuation of steroids. Neonatal lupus liver disease is a rare cause of neonatal cholestasis that can rarely present with neonatal hemochromatosis picture which unlike other causes of neonatal hemochromatosis can be reversed with steroid therapy.