Chemiluminescent detect of E. coli O157:H7 using immunological method based on magnetic nanoparticles.
The system of chemiluminescent magnetic enzyme-linked immunoassay was developed. E. coli O157:H7 was sandwiched between rabbits anti-E. coli O157:H7 polyclonal antibody-coated magnetic nanoparticles (immunomagnetic nanoparticles or IMNPs) and mouse anti-E. coli O157:H7 monoclonal antibody. Commercial alkaline phosphatase conjugated horse anti-mouse immunoglobulin (ALP-Ab) was used to bind with the monoclonal antibody, finally the chemiluminescent signals were detected by adding 3-(2'-spiroadamantane)-4-methoxy-4-(3"-phosphoryloxy)phenyl-1,2-dioxetane (AMPPD) which was the substrate reagent of ALP. Different solvents of AMPPD were compared to get an optimal chemiluminescent signal. The effects of sodium borohydride and glycine on blocking the aldehyde groups of IMNPs were compared either, and the specificity and sensitivity of this system for detecting E. coli O157:H7 were researched. The results indicated that Tris buffer was the best solvent of AMPPD, sodium borohydride was better than glycine in blocking IMNPs, and this method was of good specificity when using E. coli Top 10F' and Vibrio cholera as negative controls. The detection limit was 10(3) cells mL(-1) when the antigen solution was 1 mL, and the procedure duration was about 3 h.


Conductive Highly Filled Suspensions for an Electrochemical Dispensing Approach to Pattern Full-Area Thin Metal Layers by Physical Vapour Deposition.
This paper presents a systematic approach for the development of highly filled suspensions used for an electrochemical dispensing approach. Electrochemical dispensing is an alternative structuring process to locally pattern PVD full-area thin metal layers with the goal to create contacts on solar cells or circuit boards by anodic metal dissolution. Achieving a narrow patterned line width requires a dispensing paste with a high yield stress, a small particle size distribution and a good electrical conductivity. Therefore this work focuses on the formulation and characterization of dispensing pastes in terms of their rheological and electrical properties and their particle size distribution. Furthermore, the printing performance is evaluated in dispensing experiments. In this study, samples with a yield stress above 5000 Pa and an average particle size below 0.4 µm were produced, resulting in dispensed line widths below 100 µm with a high aspect ratio above 0.6. The lack of electrical conductivity was solved by adding KCl solution to the paste, which will add to the ionic conductivity of the NaNO3 basis paste formulation. With this approach, printed line widths down to 115 µm and etched line widths below 90 µm at high aspect ratio were achieved on 50 nm aluminum layers.


Docosahexaenoic acid preserves visual function by maintaining correct disc morphology in retinal photoreceptor cells.
Docosahexaenoic acid (DHA) has essential roles in photoreceptor cells in the retina and is therefore crucial to healthy vision. Although the influence of dietary DHA on visual acuity is well known and the retina has an abundance of DHA-containing phospholipids (PL-DHA), the mechanisms associated with DHA's effects on visual function are unknown. We previously identified lysophosphatidic acid acyltransferase 3 (LPAAT3) as a PL-DHA biosynthetic enzyme. Here, using comprehensive phospholipid analyses and imaging mass spectroscopy, we found that LPAAT3 is expressed in the inner segment of photoreceptor cells and that PL-DHA disappears from the outer segment in the LPAAT3-knock-out mice. Dynamic light-scattering analysis of liposomes and molecular dynamics simulations revealed that the physical characteristics of DHA reduced membrane-bending rigidity. Following loss of PL-DHA, LPAAT3-knock-out mice exhibited abnormalities in the retinal layers, such as incomplete elongation of the outer segment and decreased thickness of the outer nuclear layers and impaired visual function, as well as disordered disc morphology in photoreceptor cells. Our results indicate that PL-DHA contributes to visual function by maintaining the disc shape in photoreceptor cells and that this is a function of DHA in the retina. This study thus provides the reason why DHA is required for visual acuity and may help inform approaches for overcoming retinal disorders associated with DHA deficiency or dysfunction.


A comparison of African American and Latina social networks as indicators for culturally tailoring a breast and cervical cancer education intervention.
As similar cancer health disparities have been documented for African American (AA) women and Latinas, it would be important to determine whether comparable interventions could be used to increase screening among these 2 culturally different populations. This paper reports research findings comparing cultural dimensions of breast and cervical cancer as they impact Latino and AA social networks and explore the feasibility of creating outreach models that may serve both groups. An existing intervention that integrates the social roles and relationships of AA women, The Witness Project(R), is used as a framework for tailoring an intervention for Latino communities. Findings and data from focus groups and key informant interviews were collected from more than 120 Latinos in Arkansas and New York City. These findings are analyzed using the Pen-3 Model, categorized, and compared with previous social role and network information from AA women as reflected in the Witness Project(R) intervention model. The findings from this study demonstrated variations between AA women and Latinas with regard to roles and gender relationships while demonstrating similarities with regard to spiritual beliefs and attitudes toward cancer. We applied our results to culturally tailor and develop a breast and cervical cancer intervention, Esperanza y Vidatrade mark (Hope and Life), that incorporates Latino values and social relationships. This study demonstrates that a proven education and outreach model for AA women may provide a framework for creating a culturally appropriate intervention for Latinas. Further research is needed to study the efficacy of the new model. Cancer 2007. (c) 2006 American Cancer Society.


Estradiol- and testosterone-induced alterations in phosphatidylcholine and triglyceride synthesis in hepatic endoplasmic reticulum.
Pathways of phosphatidylcholine and triglyceride biosynthesis were studied in hepatic endoplasmic reticulum from castrated and noncastrated male rats pretreated with estradiol or testosterone. In vitro measurements of hepatic microsomal enzymes which catalyze phosphatidylcholine biosynthesis revealed a significant increase in the specific activity of the enzyme governing phosphatidylcholine biosynthesis by the sequential methylation of phosphatidylethanolamine in the estradiol-treated castrate animals. The specific activity of phosphorylcholine-glyceride transferase was decreased by estradiol treatment in both castrate and noncastrate animals. The specific activity of diglyceride acyltransferase, which catalyzes triglyceride biosynthesis, was decreased by estradiol pretreatment in both castrate and noncastrate animals and was increased by testosterone in the castrate animals. The changes in specific activity of the enzymes governing phosphatidylcholine biosynthesis may account for the previously noted increased in vivo incorporation of methyl groups of l-methionine into hepatic phosphatidylcholine in female and estradiol-treated animals; the data suggest that in female and estradiol-treated rats a greater proportion of hepatic phosphatidylcholine is synthesized by the stepwise methylation of phosphatidylethanolamine. The decrease in diglyceride acyltransferase specific activity seen after estradiol administration may account for the lipotropic-like effect of estradiol.


Organic nanowire fabrication and device applications.
Organic nanowires (ONWs) are flexible, stretchable, and have good electrical properties, and therefore have great potential for use in next-generation textile and wearable electronics. Analysis of trends in ONWs supports their great potential for various stretchable and flexible electronic applications such as flexible displays and flexible photovoltaics. Numerous methods can be used to prepare ONWs, but the practical industrial application of ONWs has not been achieved because of the lack of reliable techniques for controlling and patterning of individual nanowires. Therefore, an "individually controllable" technique to fabricate ONWs is essential for practical device applications. In this paper, three types of fabrication methods of ONWs are reviewed: non-alignment methods, massive-alignment methods, and individual-alignment methods. Recent research on electronic and photonic device applications of ONWs is then reviewed. Finally, suggestions for future research are put forward.


Cardioprotective effects of luteolin on ischemia/reperfusion injury in diabetic rats are modulated by eNOS and the mitochondrial permeability transition pathway.
Myocardial ischemia/reperfusion (I/R) injury in diabetes is associated with oxidative stress, endothelial nitric oxide synthase (eNOS) dysfunction, and mitochondrial collapse, whereas luteolin is known to protect the cardiovascular system against diabetes and I/R injury. Here, we investigated whether luteolin pretreatment diminishes myocardial I/R injury in diabetic rats by affecting eNOS and the mitochondrial permeability transition pore (mPTP). After diabetic rats were produced by streptozotocin treatment (65 mg/kg) for 3 weeks, luteolin (100 mg·kg·d) or L-NAME (25 mg·kg·d) was administered intragastrically for 2 weeks. Hearts were then isolated and subjected to 30 minutes of global ischemia followed by 120 minutes of reperfusion. Pretreatment with luteolin significantly improved left ventricular function and coronary flow throughout reperfusion, increased cardiac tissue viability and manganese superoxide dismutase (MnSOD) activity, and reduced coronary lactate dehydrogenase release, and the myocardial malonaldehyde level in diabetic I/R rat hearts. All these improving effects of luteolin were significantly attenuated by L-NAME. Luteolin also significantly upregulated eNOS expression in diabetic rat hearts after I/R. Ca-induced mPTP opening and mitochondrial inner membrane potential reduction were significantly inhibited in ventricular myocytes isolated from luteolin-treated diabetic rats, and this effect was attenuated by L-NAME. These findings indicate that luteolin protects the diabetic heart against I/R injury by upregulating the myocardial eNOS pathway, and downstream effects include the enhancement of MnSOD and inhibition of mPTP.


Probiotics as multifaceted oral vaccines against colon cancer: A review.
Probiotics are known as the live microorganisms that, upon adequate administration, elicit a health beneficial response inside the host. The probiotics are known as immunomodulators and exhibit anti-tumor properties. Advanced research has explored the potential use of probiotics as the oral vaccines without the latent risks of pathogenicity. Probiotic-based oral vaccines are known to induce mucosal immunity that prevents the host from several enteric infections. Probiotic bacteria have the ability to produce metabolites in the form of anti-inflammatory cytokines, which play an important role in the prevention of carcinogenesis and in the activation of the phagocytes that eliminate the preliminary stage cancer cells. This review discusses the advantages and disadvantages of using the oral probiotic vaccines as well as the mechanism of action of probiotics in colon cancer therapy. This review also employs the use of "PROBIO" database for selecting certain probiotics with immunomodulatory properties. Furthermore, the use of several probiotic bacteria as anti-colon cancer adjuvants has also been discussed in detail. Because the current studies and trials are more focused on using the attenuated pathogens instead of using the probiotic-based vaccines, future studies must involve the advanced research in exploiting the potential of several probiotic strains as adjuvants in cancer therapies.


High serum uric acid and increased risk of type 2 diabetes: a systemic review and meta-analysis of prospective cohort studies.
Current evidence suggests high serum uric acid may increase the risk of type 2 diabetes, but the association is still uncertain. The aim of the study was to evaluate the association between serum uric acid and future risk of type 2 diabetes by conducting a meta-analysis of prospective cohort studies. We conducted a systematic literature search of the PubMed database through April 2012. Prospective cohort studies were included in meta-analysis that reported the multivariate adjusted relative risks (RRs) and the corresponding 95% confidence intervals (CIs) for the association between serum uric acid and risk of type 2 diabetes. We used both fix-effects and random-effects models to calculate the overall effect estimate. The heterogeneity across studies was tested by both Q statistic and I(2) statistic. Begg's funnel plot and Egger's regression test were used to assess the potential publication bias. We retrieved 7 eligible articles derived from 8 prospective cohort studies, involving a total of 32016 participants and 2930 incident type 2 diabetes. The combined RR of developing type 2 diabetes for the highest category of serum uric acid level compared with the lowest was 1.56(95% CI, 1.39-1.76). Dose-response analysis showed the risk of type 2 diabetes was increased by 6% per 1 mg/dl increment in serum uric acid level (RR 1.06, 95% CI: 1.04-1.07). The result from each subgroup showed a significant association between serum uric acid and risk of type 2 diabetes. In sensitive analysis, the combined RR was consistent every time omitting any one study. Little evidence of heterogeneity and publication bias was observed. Our meta-analysis of prospective cohort studies provided strong evidence that high level of serum uric acid is independent of other established risk factors, especially metabolic syndrome components, for developing type 2 diabetes in middle-aged and older people.


[Who manages medical machines and tools in the home? Control of these medical devices is difficult under the cost containment plan of the health insurance system].
In 1978, on the 30th anniversary of WHO, Dr. H. Maller who was the Secretary General said, "Down with HIGH BLOOD PRESSURE" in the elderly social welfare. Since then, many kinds of sphygmomanometers and blood sugar testers have been produced and sold on a commercial basis. However, there is no one controls the quality standards of these devices. Eighty practitioners from all over the country tested the blood pressure of 13,000 patients, using 6 kinds of electric sphygmomanometer, such as MATUSITADENKOU EW-252, MATUSITASANGYOU ZH881-A, OMURON HEM703C, SHARPE NB-650, TERUMO ES-P100 and TAKEDA MEDICAL US-731. Results of the examination were not good. Fifty to 75% of the devices were accurate, but difficult for many patients to use. Data from blood sugar testers, ANTSENSE, GULTEST, GULCO. SYSTEM and GULUCOTEX, were compared. In one test, there was a 110 mg/dl difference between ANTSENSE (it's constantly high) and GULCO. SYSTEM (it's generally low); the difference was 33.7mg/dl on average, but no accidents have happened. Recently, to economize health insurance costs in Japan, the government has cut the fee paid for biochemical devices. As a result, we are concerned that incorrect management of these machines and tools may occur.


Predictive risk factors of acute kidney injury after cytoreductive surgery and cisplatin-based hyperthermic intra-peritoneal chemotherapy for ovarian peritoneal carcinomatosis.
The aim of our study was to assess the incidence and identify the predictive risk factors of acute kidney injury after cytoreductive surgery and cisplatin-based hyperthermic intra-peritoneal chemotherapy. This is a retrospective study from two centers evaluating patients with advanced or recurrent ovarian cancer who underwent cytoreductive surgery followed by cisplatin-based hyperthermic intra-peritoneal chemotherapy from January 2007 to December 2013. Patients were classified into two groups according to the occurrence of acute kidney injury, defined as a glomerular filtration rate at post-operative day 7 25% lower than at day 0. We also evaluated acute kidney injury following Risk, Injury, Failure, Lost and End-stage kidney function criteria. Univariate and multivariate analyses were conducted in order to assess the association between different variables and the occurrence of acute kidney injury. Sixty-six patients were included: 29 (44%) underwent first-line treatment and 37 (56%) were treated for recurrent disease. The incidence of post-operative acute kidney injury was 48%. After multivariate analysis, hypertension (OR 18.6; 95% CI 1.9 to 182.3; p=0.012) and low intra-operative diuresis (OR 0.5; 95% CI 0.4 to 0.8; p=0.001) were associated with acute kidney injury. The incidence of acute kidney injury after cytoreductive surgery and cisplatin-based hyperthermic intra-peritoneal chemotherapy was high. Hypertension and low intra-operative diuresis were independent risk factors for this complication. Adequate peri-operative hydration, in order to maintain correct diuresis, could decrease the occurrence of acute kidney injury in patients undergoing cytoreductive surgery plus hyperthermic intra-peritoneal chemotherapy.


SEROSURVEY OF SELECTED ARBOVIRAL PATHOGENS IN FREE-RANGING, TWO-TOED SLOTHS (CHOLOEPUS HOFFMANNI) AND THREE-TOED SLOTHS (BRADYPUS VARIEGATUS) IN COSTA RICA, 2005-07.
We screened for antibodies to 16 arboviruses in four populations of free-ranging sloths in Costa Rica. Blood samples were taken from 16 Hoffman's two-toed sloths (HTSs; Choloepus hoffmanni ) and 26 brown-throated sloths (BTSs; Bradypus variegatus ) over a 3-yr period. We used serologic assays to detect antibodies against 10 arboviruses previously described in sloths (St. Louis encephalitis [SLEV], Changuinola, Venezuelan equine encephalitis, Ilheus [ILHV], Oropouche, Mayaro, Utinga, Murutucu, Punta Toro, and vesicular stomatitis [VSV] viruses) and six arboviruses not described in sloths (Rio Grande, West Nile [WNV], eastern equine encephalitis, Piry, Munguba, and La Crosse viruses). Overall, 80% of sloths had detectable antibodies to SLEV, 67% had antibodies to ILHV, 32% to Punta Toro virus, 30% to Changuinola virus, 15% to WNV, 14% to VSV, 11% to Venezuelan equine encephalitis virus, and 10% to Rio Grande virus. No samples had detectable antibodies to the remaining eight viruses. We found a significant increase in prevalence of antibody to VSV in HTSs between 2005 and 2007, and for WNV antibody between 2005 and 2006. We found no significant differences in the prevalences of antibodies to the sampled viruses between the two locations. Antibody prevalences were significantly higher in HTSs than in BTSs for SLEV in 2005. Antibody-positive results for ILHV were likely due to cross-reaction with SLEV. The novel finding of antibodies to Rio Grande virus in sloths could be due to cross-reaction with another phlebovirus. These findings might have implications for land management and domestic animal health. Due to the nature of the study, we could not determine whether sloths could represent amplification hosts for these viruses, or whether they were only exposed and could be used as sentinel species. Further studies are needed to fully characterize arboviral exposure in sloths.


ABCB1 polymorphism as prognostic factor in breast cancer patients treated with docetaxel and doxorubicin neoadjuvant chemotherapy.
Expression of the adenosine triphosphate-binding cassette B1 (ABCB1) transporter and P-glycoprotein are associated with resistance to anticancer drugs. The purpose of this study was to investigate the role of single nucleotide polymorphism in the ABCB1 and CYP3A genes in breast cancer patients who were treated with neoadjuvant chemotherapy. Stage II/III breast cancer patients were treated with three cycles of neoadjuvant, after which the patients received curative surgery and adjuvant chemotherapy. The polymorphisms of ABCB1 and CYP3A were genotyped. The correlation of polymorphism of ABCB1, CYP3A, and clinical outcomes was analyzed. Among the 216 patients, ABCB1 3435TT genotype had a longer overall survival (OS). than CC/CT. Multivariate analyses demonstrated that good PS, invasive ductal carcinoma, non-triple negative phenotype and initial operable stage were significantly associated with a lower death risk. ABCB1 3435TT genotype had a higher AUC than CC/CT for docetaxel. These higher AUCs in the C3435TT was associated with increased toxicities of neutropenia and diarrhea. This study showed that the genetic polymorphism of ABCB1 C3435T might be associated with a longer OS. Our results also suggest that the prediction of docetaxel toxicity might be possible for C3435T polymorphism. This study results provides valuable information on individualized therapy according to genotypes.


The management of depression, and the use of lofepramine in the elderly.
Treatment of depression in the elderly compared with younger patients is complicated by a number of additional factors. The main differential factors in the elderly are an increased incidence and severity of adverse life events and a parallel increase in social disadvantages. Associated physical problems are much more frequently encountered, and there is a striking increase in suicidal potential--with the elderly accounting for some 12 per cent of the population but being involved in some 33 per cent of all completed suicides. While some pessimistic views have been expressed about the outcome of chemotherapy, this is for many patients the cornerstone of treatment, with the older tricyclic antidepressants still used extensively. However, these agents have serious disadvantages. They are highly toxic in overdosage, with pronounced anticholinergic actions and marked adverse effects on the cardiovascular system in therapeutic dosage. The newer non-tricyclic antidepressants have revealed further problems, with two of these agents being withdrawn because of serious side effects. Against this background, the introduction of the modified tricyclic compound lofepramine was of major interest in the light of its much reduced toxicity and anticholinergic effects when compared with older antidepressants. The results of a retrospective study involving the use of lofepramine in a series of 210 elderly depressives (mean age 75.8 years) suggests that a majority of such patients will respond to energetic treatment. Seventy per cent of the patients showed a response ranging from good to complete remission of symptoms and overall tolerability was excellent.


Effect of nonpersistent pesticides on estrogen receptor, androgen receptor, and aryl hydrocarbon receptor.
Nonpersistent pesticides are considered less harmful for the environment, but their impact as endocrine disruptors has not been fully explored. The pesticide Switch was applied to grape vines, and the maximum residue concentration of its active ingredients was quantified. The transactivation potential of the pesticides Acorit, Frupica, Steward, Reldan, Switch, Cantus, Teldor, and Scala and their active compounds (hexythiazox, mepanipyrim, indoxacarb, chlorpyrifos-methyl, cyprodinil, fludioxonil, boscalid, fenhexamid, and pyrimethanil) were tested on human estrogen receptor α (ERα), androgen receptor (AR) and arylhydrocarbon receptor (AhR) in vitro. Relative binding affinities of the pure pesticide constituents for AR and their effect on human breast cancer and prostate cancer cell lines were evaluated. Residue concentrations of Switch's ingredients were below maximum residue limits. Fludioxonil and fenhexamid were ERα agonists (EC50 -values of 3.7 and 9.0 μM, respectively) and had time-dependent effects on endogenous ERα-target gene expression (cyclin D1, progesterone receptor, and nuclear respiratory factor 1) in MCF-7 human breast cancer cells. Fludioxonil, mepanipyrim, cyprodinil, pyrimethanil, and chlorpyrifos-methyl were AhR-agonists (EC50 s of 0.42, 0.77, 1.4, 4.6, and 5.1 μM, respectively). Weak AR binding was shown for chlorpyrifos-methyl, cyprodinil, fenhexamid, and fludioxonil. Assuming a total uptake which does not take metabolism and clearance rates into account, our in vitro evidence suggests that pesticides could activate pathways affecting hormonal balance, even within permitted limits, thus potentially acting as endocrine disruptors.


Treatment of grade III acromioclavicular joint injuries: a systematic review.
Although nonoperative treatment is considered the standard of care for the treatment of Grade I and II acromioclavicular (AC) joint injuries, the treatment of Grade III injuries is controversial. There are as many methods of nonoperative treatment as there are for operative stabilization. Most of the literature represents Level IV evidence with very few Level II and III studies upon which to base decisions. A systematic review of the English-language literature was performed to determine if Grade III AC joint separations are best treated operatively or nonoperatively. Based on limited low-evidence, nonoperative treatment was deemed more appropriate than traditional nonoperative treatments because the results of the latter were not clearly better and were associated with higher complication rates, longer convalescence, and longer time away from work and sport.


[Thrombotic microangiopathy after kidney transplantation].
The term thrombotic microangiopathy (TMA) encompasses different disturbances that are usually classified as thrombotic thrombocytopenic purpura (TTP) or haemolytic-uraemic syndrome (HUS). These syndromes are characterized by thrombocytopenia, microangipathic haemolytic anaemia, neurological deficits and renal failure. Etiology of TMA include exotoxins, drug toxicity (cyclosporin, tacrolimus, ticlopidine, clopidogrel, mitomycin), but also familiar forms associated with deficiency of factor H (HUS) or vWF protease activity (TTP). TMA in renal transplant recipients may evolve de novo or may recur in patients who were diagnosed with TMA as the primary renal disease. We present a case of renal transplant recipient with ESRD of unknown etiology, who was diagnosed with TMA 3 years after transplantation. After discontinuation of cyclosporine, she was treated with therapeutic plasma exchange (TPE). Cytomegalovirus reactivation demanded discontinuation of the chronic program of TPE, what was followed by worsening of graft function and demand for dialysis one year after the diagnosis of TMA. Patients with TMA should be carefully followed-up after renal transplantation for the signs of disease recurrence. Withdrawal of precipitating factors is of outstanding importance. TPE is used to limit the endothelial damage and to limit the microangiopathic process. However, its efficacy is unclear. Our case demonstrates that TPE may improve graft survival, with the possibility of inducing opportunistic infections. International registries are needed to establish the guidelines for follow-up and treatment of renal transplant recipients with TMA.


Development of an isotope dilution assay for precise determination of insulin, C-peptide, and proinsulin levels in non-diabetic and type II diabetic individuals with comparison to immunoassay.
We describe the application of a stable isotope dilution assay (IDA) to determine precise insulin, C-peptide, and proinsulin levels in blood by extraction from serum and quantitation by mass spectrometry using analogues of each target protein labeled with stable isotopes. Insulin and C-peptide levels were also determined by immunoassay, which gave consistently higher results than by IDA, the relative difference being larger at low concentrations. Insulin, C-peptide, and proinsulin levels were all shown by IDA to be higher in type II diabetics than in non-diabetics, with mean values rising from 22 (+/- 2) to 92 (+/- 8), 335 (+/- 11) to 821 (+/- 24), and 6 (+/- 1) to 37 (+/- 3) pM, respectively. Interestingly, the ratio between IDA and immunoassay values for insulin levels increased from 1.3 in non-diabetics to 1.7 in type II diabetics. The ratio between proinsulin and insulin levels by IDA increased from 0.24 in non-diabetics to 0.36 in type II diabetics, whereas the ratio between C-peptide and insulin levels by IDA decreased from 17.6 to 10.7. This disproportionate change in protein levels between different types of individuals has implications for the metabolism of insulin in the diabetics studied (type II) and suggests that C-peptide levels are not always a reliable guide as to pancreatic insulin secretion. In addition, levels of the 33-residue C-peptide (partially trimmed form) were shown to be less than 10% that of the fully trimmed 31-residue C-peptide levels, and we tested IDA in a clinical context by two post-pancreatic graft studies. IDA was shown to give direct, positive identification of the target protein with unrivaled accuracy, avoiding many of the problems associated with present methodology for protein determination.


A Highly Sensitive Colorimetric Method for Copper Ions Detection Based on Controlling the Peroxidase-like Activity of Au@Pt Nanocatalysts.
In this study, a sensitive colorimetric method for the detection of copper ion (Cu2+) was developed based on controlling the peroxidase-like activity of (gold core)@(ultrathin platinum shell) nanocatalysts (Au@Pt-NCs). It was found that D-penicillamine can effectively inhibit the activity of Au@Pt-NCs. After being incubated with Cu2+, D-penicillamine lost inhibition toward the catalytic ability of Au@Pt-NCs. Based on the above interaction, a colorimetric detection of Cu2+ was develop by measuring the colorimetric signal variation of the H2O2-3,3',5,5'-tetramethylbenzidine (TMB) reaction. This method exhibited high sensitivity and selectivity toward Cu2+ over a panel of other metal ions. The detection limit of this method was 3.7 nM and the linear range was 20 - 300 nM. Moreover, 20 nM Cu2+ can be distinguished directly by the naked eye. Furthermore, this method was applied to the analysis of water samples with good accuracy. These results demonstrated the excellent application potential of the method.


Metal elements and gene expression.
The transcriptional regulation of genes by metals is a biological function separate from structural and catalytic roles for metals in gene expression. Each of these functions relies on metals that enter cells from metabolic compartments derived from and influenced by the dietary metal supply. The intracellular metal pools provide an available source for binding to metalloregulatory proteins for transcriptional regulation. These proteins bind MRE sequences found in the promoters of some genes. The distribution of MRE sequences and of metalloregulatory proteins extends from microbial to mammalian systems. The bulk of the data on metal regulation of mammalian gene expression is from the perspective of positive transcriptional regulation. Nevertheless, negative regulation by metals could potentially occur. Transcriptional regulation of genes by nutritionally important metals must be viewed in the context of the other roles of metals in cellular structure and function. Investigators are rapidly delineating the involvement of metals in molecular biology in general and in gene expression in particular.


Treatment outcomes and prognostic factors in mexican patients with endometrial carcinoma with emphasis on patients receiving radiotherapy after surgery: an institutional perspective.
Aim. To analyze the clinical characteristics and treatment outcomes in patients with endometrial carcinoma treated in a Latin American institute with emphasis in patients receiving adjuvant radiotherapy. Methods. A total of 412 patients with endometrial carcinoma admitted to our hospital between 1998 and 2008 were evaluated, retrospectively. The mean age was 55 years (28-87). Two hundred seventy patients received RT following surgery. Stage distribution was as follows: 221 patients (54%) stage I, 86 patients (21%) stage II, and 103 patients (24.5%) stage III and 2 patients (0.5%) stage IVA. Results. Overall survival rate was 95% at 2 years, 84% at 5 years, and 79% at 10 years. By the end of followup, 338 patients (82%) were disease-free, and 13 (3%) were alive with disease. Univariate and multivariate analyses identified age, grade, serosal and adnexial involvement as significant predictors for overall survival. Conclusion. The results of our study suggests that early-stage, low-grade endometrial cancer with no risk factors should not receive external beam radiotherapy, intermediate risk patients should receive only vaginal vault brachytherapy, and the use of chemotherapy with radiotherapy for patients high-risk and advanced-stage carcinoma the addition of radiotherapy is associated with a better survival being an effective therapeutic option.


[A study of sensitization and symptoms in adult asthmatics who keep cat and dog].
We studied hypersensitivity to cats and dogs in three hundred adult asthmatics who kept them. Some findings were noted as follows. 1) The mean duration for which cats were kept was 6.2 +/- 10.1 (1 S.D.) years and that for dogs was 4.2 +/- 9.6 (1 S.D.) years. 2) The positive rate in intradermal tests to dog dander was 7% and to cat hair-epithelium 32%. The positive RAST (score > or = 2) rate to cat epithelium was 36.1%, to dog dander 31.6% and to dog epithelium 7.3% respectively. 3) Eleven to 18% of the dog keepers and 23 to 36% of the cat keepers whose RAST score were positive were aware of the relationship between pets and asthma, specifically concerning eye and nose symptoms. 4) Thirty percent of the cat and dog keepers had become sensitized to them after keeping them for under one year. The positive RAST rate was unchanged in those who kept Japanese native dogs but increased in those who kept foreign breeds after 3 to 6 years. The rate of sensitization rate to cats tended to increase along with the period for which they were kept. 5) Dog dander RAST scores among the foreign breed keepers were significantly higher than those among the native dog keepers. If the dog breed was the same, the RAST score was not higher if the dog was kept indoors than if it was kept outdoors. We concluded that a possible reason why the RAST scores were higher among those who kept foreign breeds was that foreign breeds have stronger allergenicity.


Activity-dependent NMDA receptor degradation mediated by retrotranslocation and ubiquitination.
The extracellular N-terminal domain (NTD) is the largest region of NMDA receptors; however, biological roles for this ectodomain remain unknown. Here, we determined that the F-box protein, Fbx2, bound to high-mannose glycans of the NR1 ectodomain. F-box proteins specify ubiquitination by linking protein substrates to the terminal E3 ligase. Indeed, ubiquitination of NR1 was increased by Fbx2 and diminished by an Fbx2 dominant-negative mutant. When expressed in hippocampal neurons, this Fbx2 dominant-negative mutant augmented NR1 subunit levels and NMDA receptor-mediated currents in an activity-dependent fashion. These results suggest that homeostatic control of synaptic NR1 involves receptor retrotranslocation and degradation by the ubiquitin-proteasome pathway.


Colliding Bose-Einstein condensates to observe Efimov physics.
We explore the manifestation of Efimov physics through the collision energy dependence of the three-body scattering observables and propose that it can be measured by observing atom loss in collisions of Bose-Einstein condensates. Our study shows that log-periodic Efimov features in the scattering observables extend beyond the usual threshold regime to nonzero collision energies and result from two interfering pathways. Further, these oscillations have a one-to-one connection with the scattering length oscillations at zero energy and thus to Efimov states themselves.


Critical serum creatinine values in very preterm newborns.
Renal failure in neonates is associated with an increased risk of mortality and morbidity. But critical values are not known. To define critical values for serum creatinine levels by gestational age in preterm infants, as a predictive factor for mortality and morbidity. This was a retrospective study of all preterm infants born before 33 weeks of gestational age, hospitalized in Nantes University Hospital NICU between 2003 and 2009, with serum creatinine levels measured between postnatal days 3 to 30. Children were retrospectively randomized into either training or validation set. Critical creatinine values were defined within the training set as the 90(th) percentile values of highest serum creatinine (HSCr) in infants with optimal neurodevelopmental at two years of age. The relationship between these critical creatinine values and neonatal mortality, and non-optimal neural development at two years, was then assessed in the validation set. The analysis involved a total of 1,461 infants (gestational ages of 24-27 weeks (n=322), 28-29 weeks (n=336), and 30-32 weeks (803)), and 14,721 creatinine assessments. The critical values determined in the training set (n=485) were 1.6, 1.1 and 1.0 mg/dL for each gestational age group, respectively. In the validation set (n=976), a serum creatinine level above the critical value was significantly associated with neonatal mortality (Odds ratio: 8.55 (95% confidence interval: 4.23-17.28); p<0.01) after adjusting for known renal failure risk factors, and with non-optimal neurodevelopmental outcome at two years (odds ratio: 2.06 (95% confidence interval: 1.26-3.36); p=0.004) before adjustment. Creatinine values greater than 1.6, 1.1 and 1.0 mg/dL respectively at 24-27, 28-29, 30-32 weeks of gestation were associated with mortality before and after adjustment for risk factors, and with non-optimal neurodevelopmental outcome, before adjustment.


The heterogeneous chemical kinetics of NO3 on atmospheric mineral dust surrogates.
Uptake experiments of NO3 on mineral dust powder were carried out under continuous molecular flow conditions at 298 +/- 2 K using the thermal decomposition of N2O5 as NO3 source. In situ laser detection using resonance enhanced multiphoton ionization (REMPI) to specifically detect NO2 and NO in the presence of N2O5, NO3 and HNO3 was employed in addition to beam-sampling mass spectrometry. At [NO3] = (7.0 +/- 1.0) x 10(11) cm(-3) we found a steady state uptake coefficient gamma(ss) ranging from (3.4 +/- 1.6) x 10(-2) for natural limestone to (0.12 +/- 0.08) for Saharan Dust with gamma(ss) decreasing as [NO3] increased. NO3 adsorbed on mineral dust leads to uptake of NO2 in an Eley-Rideal mechanism that usually is not taken up in the absence of NO3. The disappearance of NO3 was in part accompanied by the formation of N2O5 and HNO3 in the presence of NO2. NO3 uptake performed on small amounts of Kaolinite and CaCO3 leads to formation of some N2O5 according to NO((3ads)) + NO(2(g)) --> N2O(5(ads)) --> N2O(5(g)). Slow formation of gas phase HNO3 on Kaolinite, CaCO3, Arizona Test Dust and natural limestone has also been observed and is clearly related to the presence of adsorbed water involved in the heterogeneous hydrolysis of N2O(5(ads)).


Gender, Internet use, and sexual behavior orientation among young Nigerians.
This study examined the influence of gender and Internet use on the sexual behavior orientation of young adults in Nigeria. Using an ex-post-facto design, data were collected from a total of 231 participants. Results of the hierarchical regression model provided support for the influence of gender and Internet use on sexual behavior orientation among young Nigerians. Further, results also revealed an interaction effect; as the use of the Internet increased, male participants reported a greater extent of risky sexual behavior orientation than their female counterparts. The findings were explained in the context of the theoretical foundations of the study, while practical implications for combating youths' risky sexual behavior orientation were highlighted.


[Respiratory distress due to pulmonary hemorrhage in leptospirosis].
Two patients who lived in Buenos Aires suburbs died from leptospirosis in July 2000 and March 2001. They developed a nonspecific febrile illness followed by hemorrhagic pneumonia and respiratory distress in absence of typical manifestations such as jaundice, nephropathy, thrombocitopenia or hemorrhages in other organs. In the house and surroundings of one patient rodents were captured and three strains of leptospira, serogroup Icterohaemorrhagiae were isolated. Laboratory guinea pigs were inoculated and they were sacrificed as soon as respiratory symptoms appeared. Necropsy showed primary lung injury, which was similar to the histopathological lesions found in one of the patients. Neither jaundice, nor renal damage was found. Pericardiac hemorrhages were considered as a possible cause of cardiopulmonary collapse. This clinical form has not been reported previously in this region, where conditions are indeed suitable for the human illness to appear.


The adaptor protein AP-3 is required for CD1d-mediated antigen presentation of glycosphingolipids and development of Valpha14i NKT cells.
Relatively little is known about the pathway leading to the presentation of glycolipids by CD1 molecules. Here we show that the adaptor protein complex 3 (AP-3) is required for the efficient presentation of glycolipid antigens that require internalization and processing. AP-3 interacts with mouse CD1d, and cells from mice deficient for AP-3 have increased cell surface levels of CD1d and decreased expression in late endosomes. Spleen cells from AP-3-deficient mice have a reduced ability to present glycolipids to natural killer T (NKT) cells. Furthermore, AP-3-deficient mice have a significantly reduced NKT cell population, although this is not caused by self-tolerance that might result from increased CD1d surface levels. These data suggest that the generation of the endogenous ligand that selects NKT cells may also be AP-3 dependent. However, the function of MHC class II-reactive CD4+ T lymphocytes is not altered by AP-3 deficiency. Consistent with this divergence from the class II pathway, NKT cell development and antigen presentation by CD1d are not reduced by invariant chain deficiency. These data demonstrate that the AP-3 requirement is a particular attribute of the CD1d pathway in mice and that, although MHC class II molecules and CD1d are both found in late endosomes or lysosomes, different pathways mediate their intracellular trafficking.


On the reactivity of tetrakis(trifluoromethyl)cyclopentadienone towards carbon-based Lewis bases.
The reactivitiy of tetrakis(trifluoromethyl)cyclopentadienone towards different C-based Lewis bases, such as N-heterocyclic carbenes (NHC), ylides and isonitriles, are reported. While sterically not hindered carbenes were found to yield kinetic adducts by regiospecific nucleophilic attack at the position adjacent to the carbonyl group of the ketone, bulkier nucleophiles afforded the thermodynamically more stable O-bridged zwitterions. Interestingly, isonitriles were found to dimerize and trimerize under the same reaction conditions, forming bicyclic products that evolve differently depending on the nature of the substituents.


[Effect of tacrolimus on the pharmacokinetics and glucuronidation of SN-38, an active metabolite of irinotecan].
The present study has investigated the effect of tacrolimus on the pharmacokinetics of an active metabolite of irinotecan (CPT-11), 7-ethyl-10-hydroxy-camptothecin (SN-38) and SN-38 glucuronide (SN-38G) in rats. The effect of tacrolimus on SN-38 glucuronidation was also investigated in human and rat liver microsomes. When tacrolimus (0.5 mg/kg) was intravenously injected in rats 15 min before intravenous injection of CPT-11 (5 mg/kg), tacrolimus decreased the plasma concentration of SN-38G. Tacrolimus significantly decreased the area under plasma concentration-time curve (AUC) of SN-38G without change in the mean residence time. On the contrary, significant changes in the pharmacokinetic parameters of SN-38 were not observed. SN-38 glucuronidation in human and rat liver microsomes was inhibited dose-dependently by the presence of tacrolimus and the 50% inhibition concentration (IC50) values of tacrolimus in rat and human liver microsomes were 10.33 μM and 3.58 μM, respectively. When the inhibition type was determined by Lineweaver-Burk and Dixon plots, the inhibition was noncompetitive and the calculated inhibition constant (Ki) values for rat and human liver microsomes were 12.57 μM and 3.88 μM, respectively. These findings suggest that tacrolimus inhibits UGT1A1-mediated SN-38 glucuronidation. Considering the IC50 and Ki values for tacrolimus, it is likely that tacrolimus does not alter the pharmacokinetics of SN-38 and SN-38G at the clinically used dosages, suggesting the possibility that tacrolimus can use safely for cancer patients with irinotecan chemotherapy.


Single-Incision Laparoscopic Nontraumatic Left Lateral Diaphragmatic Hernia Repair.
Diaphragmatic hernia is a quite uncommon disease, being congenital or posttraumatic. Its diagnosis is frequently accidental. Surgical treatment can be performed through the abdomen as well as through the chest. Laparoscopy and thoracoscopy offer a surgical benefit because of reduced wall trauma and added advantages of minimally invasive surgery. Besides the improved cosmetic result, transumbilical single-incision laparoscopy can add other advantages to minimally invasive surgery like reduced postoperative pain, shorter hospital stay, and improved patient's comfort. The authors describe the technique of transumbilical single-incision laparoscopic suture and mesh reinforcement for a nontraumatic left lateral diaphragmatic hernia, discovered accidentally in a 45-year-old male.


Immunohistochemical detection of intermediate filament proteins in formalin fixed normal and neoplastic canine tissues.
Normal and well differentiated neoplastic canine tissues were immunohistochemically stained for keratin, vimentin and desmin intermediate filament proteins using commercially available monoclonal antibodies. Keratin was detected in 56 of 57 carcinomas, vimentin in 59 of 62 sarcomas and desmin in three of four muscle cell tumors. Most normal and neoplastic tissues expressed only one type of intermediate filament; exceptions were one hemangiosarcoma and one pulmonary carcinoma in which there was coexpression of vimentin and keratin proteins. Since immunohistochemical detection of intermediate filaments has tissue-specific distribution in the majority of well differentiated canine neoplasms, these stains may be useful in the differential diagnosis of anaplastic canine tumors. However, the monoclonal antibodies to cytokeratin which were tested in this study failed to detect intermediate filaments in liver, pancreas and salivary glands which suggests that these antibodies may also be unable to detect epithelial tumors derived from these tissues. In addition, in nine neoplasms, the normal tissues adjacent to neoplastic cells failed to stain for the intermediate filament normally expressed. When this occurs, evaluation of intermediate filament expression is invalid for the determination of tissue of origin of the neoplastic cells.


Microwave-assisted synthesis of medicinally relevant indoles.
Indoles represent an important structural class in medicinal chemistry with broad spectrum of biological activities. The synthesis of indoles, therefore, has attracted enormous attention from synthetic chemists. Microwave methods for the preparation of indole analogs have been developed to speed up the synthesis, therefore, microwave assisted organic synthesis (MAOS) in controlled conditions is an invaluable technique for medicinal chemistry. In this review, indole forming classical reactions such as Fischer, Madelung, Bischler-Mohlau, Batcho-Leimgruber, Hemetsberger-Knittel, Graebe-Ullmann, Diels-Alder and Wittig type reactions using microwave radiation has been summarized. In addition, metal mediated cyclizations along with solid phase synthesis of indoles have been discussed.


Effects of furosemide on renal oxygen consumption after ischemia in normal and streptozotocin diabetic rats.
Normal and streptozotocin diabetic rats were subjected to ischemic injury by unilateral renal artery occlusion for 60 min. The cortical and the medullary oxygen consumption (QO2) in the postischemic and the control, contralateral nonischemic, kidneys were measured 1 h, 1 day, and 1, 2 and 4 weeks for normal rats and 1 day, and 1 and 4 weeks for diabetic rats after ischemia. The effects of furosemide on QO2 of the cortex and the medulla of normal and diabetic rats were studied. The diabetic kidney was more vulnerable to ischemic injury than the normal kidney. Furosemide-sensitive active transport function in the medulla of the diabetic kidney was higher than that of the normal kidney. Furosemide did not decrease the cortical QO2 significantly in the control and the postischemic kidneys of normal and diabetic rats. In contrast, the medullary QO2 of the control kidney in both rats was significantly reduced by furosemide at every period after ischemia. In the medullary QO2 of the postischemic kidney, there were no significant decreases at any period after ischemia in the diabetic rats and only after a 1-hour period for normal rats. However, 4 weeks after ischemia, there was no statistically significant difference in the medullary QO2 inhibition by furosemide between the control and the postischemic kidneys in both normal and diabetic rats. We conclude that the furosemide-sensitive active transport function in the medulla recovers by the 4th week after ischemia in normal and diabetic rats.


[The McBride operation of hallux valgus in adolescents (author's transl)].
Severe Hallux valgus deformity in adolescents and young adults has been treated by the McBride operation in 53 cases during the period from 1965 to 1974. With 85% good results in our material this type of operation is very satisfactory. Other authors have made the same experience. The principles and technique of this soft tissue correction are described and the results of reexamination presented.


[Ultrasonography in primary malignant lymphoma of the thyroid].
We analyzed retrospectively the sonographic appearance of eight cases of primary malignant lymphoma of the thyroid. Sonography showed hypoechoic masses replacing thyroid parenchyma with posterior acoustic enhancement. A hypoechoic and/or nearly anechoic confluent nodular appearance characterized malignant lymphoma of the thyroid.


Issues in nursing. Royal College of Nursing. Nursing care for gay men and lesbians.
This article discusses discrimination and prejudice towards lesbian and gay patients, and outlines the RCN's commitment to developing and promoting good nursing practice for this group of clients, and to the support of any nurses who experience difficulties in developing their practice in this area.


Novel PPARα agonist MHY553 alleviates hepatic steatosis by increasing fatty acid oxidation and decreasing inflammation during aging.
Hepatic steatosis is frequently observed in obese and aged individuals. Because hepatic steatosis is closely associated with metabolic syndromes, including insulin resistance, dyslipidemia, and inflammation, numerous efforts have been made to develop compounds that ameliorate it. Here, a novel peroxisome proliferator-activated receptor (PPAR) α agonist, 4-(benzo[d]thiazol-2-yl)benzene-1,3-diol (MHY553) was developed, and investigated its beneficial effects on hepatic steatosis using young and old Sprague-Dawley rats and HepG2 cells.Docking simulation and Western blotting confirmed that the activity of PPARα, but not that of the other PPAR subtypes, was increased by MHY553 treatment. When administered orally, MHY553 markedly ameliorated aging-induced hepatic steatosis without changes in body weight and serum levels of liver injury markers. Consistent with in vivo results, MHY553 inhibited triglyceride accumulation induced by a liver X receptor agonist in HepG2 cells. Regarding underlying mechanisms, MHY553 stimulated PPARα translocation into the nucleus and increased mRNA levels of its downstream genes related to fatty acid oxidation, including CPT-1A and ACOX1, without apparent change in lipogenesis signaling. Furthermore, MHY553 significantly suppresses inflammatory mRNA expression in old rats. In conclusion, MHY553 is a novel PPARα agonist that improved aged-induced hepatic steatosis, in part by increasing β-oxidation signaling and decreasing inflammation in the liver. MHY553 is a potential pharmaceutical agent for treating hepatic steatosis in aging.


Hunters and hunting across indigenous and colonist communities at the forest-agriculture interface: an ethnozoological study from the Peruvian Amazon.
Wildlife has been traditionally used by forest communities as a source of protein, and the Peruvian Amazon is no exception. The articulation of colonist and indigenous communities to urban centers and markets results in changes in livelihood strategies and impacts on wildlife populations. To address the threat of overhunting and forest conversion, we provide a generalized characterization of colonist and indigenous communities and their hunting activities near Pucallpa, Ucayali, Peru. A semi-structured household survey was conducted to characterize hunters and describe their prey collections. The data were analyzed by conducting a Kruskal-Wallis test, a multiple regression analysis, and by estimating the harvest rate (H). Less wealthy households were more actively engaged in hunting for food security and as a livelihood strategy. Additionally, older hunters were associated with higher hunting rates. Although the percentage of hunters was relatively low, estimated hunting rates suggest overharvesting of wildlife. Lowland pacas (Cuniculus paca) were the most frequently hunted prey, followed by red brocket deer (Mazama americana) and primates. While hunting intensity was not significantly different between indigenous and colonist communities, hunting rate disparities suggest there are different types of hunters (specialized vs. opportunistic) and that prey composition differs between communities. Close monitoring of wildlife populations and hunting activities is ideal for more accurately determining the impact of hunting on wildlife population and in turn on forest health. In lack of this type of information, this study provides insight of hunting as a shifting livelihood strategy in a rapidly changing environment at the forest/agriculture frontier.


Central nervous system effects of arachidonic acid, PGE2, PGF2 alpha, PGD2 and PGI2 on gastric secretion in the rat.
The effects of arachidonic acid, prostaglandin E2 (PGE2), PGF2 alpha, PGD2 and PGI2 on gastric secretion (acid, pepsin and volume) after intracerebroventricular administration were investigated in conscious, pylorus-ligated rats. Arachidonic acid 30-1000 micrograms had no effect on gastric secretion. PGE2 3 and 10 micrograms, reduced gastric secretion as measured 1 hour after injection, although the inhibition induced by 3 micrograms disappeared by 2 h. PGF2 alpha 10 and 30 micrograms, inhibited gastric secretion as measured after 1 h, whereas no change was observed in the gastric contents collected 2 h after 10 micrograms of PGF2 alpha. Intramuscular injection of 30 micrograms of PGF2 alpha had no effect on gastric secretion. Intracerebroventricular administration of 1-30 micrograms of PGD2 or PGI2 had no effect on gastric secretion. The results indicate that PGE2 and PGF2 alpha have a potent central antisecretory action in conscious, pylorus-ligated rats, whereas arachidonic acid, PGD2 and PGI2 do not have any central effects on gastric secretion. It is suggested that PGE2 and PGF2 alpha may be involved in the central nervous system control of gastric secretion.


Role of neoplastic monocyte-derived fibrocytes in primary myelofibrosis.
Primary myelofibrosis (PMF) is a fatal neoplastic disease characterized by clonal myeloproliferation and progressive bone marrow (BM) fibrosis thought to be induced by mesenchymal stromal cells stimulated by overproduced growth factors. However, tissue fibrosis in other diseases is associated with monocyte-derived fibrocytes. Therefore, we sought to determine whether fibrocytes play a role in the induction of BM fibrosis in PMF. In this study, we show that BM from patients with PMF harbors an abundance of clonal, neoplastic collagen- and fibronectin-producing fibrocytes. Immunodeficient mice transplanted with myelofibrosis patients' BM cells developed a lethal myelofibrosis-like phenotype. Treatment of the xenograft mice with the fibrocyte inhibitor serum amyloid P (SAP; pentraxin-2) significantly prolonged survival and slowed the development of BM fibrosis. Collectively, our data suggest that neoplastic fibrocytes contribute to the induction of BM fibrosis in PMF, and inhibiting fibrocyte differentiation with SAP may interfere with this process.


Timeless preserves telomere length by promoting efficient DNA replication through human telomeres.
A variety of telomere protection programs are utilized to preserve telomere structure. However, the complex nature of telomere maintenance remains elusive. The Timeless protein associates with the replication fork and is thought to support efficient progression of the replication fork through natural impediments, including replication fork block sites. However, the mechanism by which Timeless regulates such genomic regions is not understood. Here, we report the role of Timeless in telomere length maintenance. We demonstrate that Timeless depletion leads to telomere shortening in human cells. This length maintenance is independent of telomerase, and Timeless depletion causes increased levels of DNA damage, leading to telomere aberrations. We also show that Timeless is associated with Shelterin components TRF1 and TRF2. Timeless depletion slows telomere replication in vitro, and Timeless-depleted cells fail to maintain TRF1-mediated accumulation of replisome components at telomeric regions. Furthermore, telomere replication undergoes a dramatic delay in Timeless-depleted cells. These results suggest that Timeless functions together with TRF1 to prevent fork collapse at telomere repeat DNA and ensure stable maintenance of telomere length and integrity.


Diversity among beta-tubulins: a carboxy-terminal domain of yeast beta-tubulin is not essential in vivo.
Sequences of genes for beta-tubulins from many different organisms demonstrate that they encode highly conserved proteins but that these proteins diverge considerably at their carboxyl termini. The patterns of interspecies conservation of this diversity suggest that it may have functional significance. We have taken advantage of the properties of Saccharomyces cerevisiae to test this hypothesis in vivo. The sole beta-tubulin gene of this species is one of the most divergent of all beta-tubulins and encodes 12 amino acids which extend past the end of most other beta-tubulin molecules. We have constructed strains in which the only beta-tubulin gene is an allele lacking these 12 codons. We show here that this carboxy-terminal extension is not essential. The absence of these 12 amino acids had no effect on a number of microtubule-dependent functions, such as mitotic and meiotic division and mating. It did confer dominant supersensitivity to a microtubule-depolymerizing drug.


Detection and Analysis of the Oral Flora in Patients with Recurrent Aphthous Stomatitis.
The present study detected differences in the oral mucosal flora in healthy people and patients diagnosed with recurrent aphthous stomatitis (RAS) using the 16S ribosomal RNA high-throughput sequencing (rRNA-seq). All samples were collected from the lower lip mucosa of 100 healthy individuals and 100 patients with RAS. After the extraction, DNA was subjected to PCR amplification for the bacterial 16S rRNA gene, before subjecting to high-throughput sequencing, and matched to a database. Most bacterial species and most unique bacteria were from the healthy control group, and the amount of operational taxonomic units (OTUs) calculated was similar in the ulcer and nonulcer sites. Firmicutes, Proteobacteria, and Bacteroidetes were most abundant in the healthy group and in ulcer, nonulcer, and healed ulcer sites at the phylum level. Meanwhile, the number of Prevotella was significantly elevated in ulcer sites (P < 0.05). Healthy people had more species of bacteria inhabiting their oral mucosa than did RAS patients, and patients with ulcers had the lowest abundance of bacterial species. We suggest that the number of Prevotella is associated with RAS.


Patient-reported Outcomes and Quality of Life After Treatment of Choroidal Melanoma: A Comparison of Enucleation Versus Radiotherapy in 1596 Patients.
To test the hypothesis that patients treated with radiotherapy for choroidal melanoma enjoy better quality of life (QoL) than patients who have undergone enucleation. In this nonrandomized study, patients with choroidal melanoma treated at the Royal Liverpool University Hospital, Liverpool, UK, were invited to complete QoL questionnaires approximately 6 months postoperatively and then on each anniversary of their primary treatment. These instruments consisted of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-OPT30 questionnaire, Hospital Anxiety & Depression Scale, and the Functional Assessment of Cancer Treatment questionnaire. Patient-reported outcomes were correlated with demographics, ocular treatment, social factors, presenting tumor and ocular status, self-reported general health, marital status, and employment status. The 1596 patients were treated with radiotherapy (72.3%) or enucleation (27.7%). Enucleation was associated with male sex (χ2, P = .004), older age (t test, P < .001), larger tumor diameter (t test, P < .001), monosomy 3 (χ2, P < .001), depression (linear regression, 95% confidence interval [CI], .17 to 1.01), and reduced physical and functional well-being (linear regression, 95% CI, -1.14 to -0.12 and -1.96 to -0.47), respectively. Poor QoL was attributed to the ocular disease by 21% and 20% of enucleated and irradiated patients, respectively (χ2, P = .938). Patient-reported outcomes and QoL were worse in patients who had undergone primary enucleation for choroidal melanoma. These outcomes may partly have been caused by factors predisposing to enucleation rather than enucleation itself, because enucleated patients tended to be older, with more advanced disease at presentation, and a worse prognosis for survival. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.


[Lymphomas associated with HIV infection in patients at the Hospital San Borja Arriarán /Fundación Arriarán 2001-2008, Santiago, Chile].
Hodgkin lymphomas (HL) and non Hodgkin lymphomas (NHL) are frequently associated to acquired immunodeficiency syndrome in adults. To systematize the clinical features and histological characteristics of lymphomas in AIDS patients, its treatment and outcomes in our institution. Retrospective analysis of patients with HIV-associated lymphoma between January 2001 and December 2008 at the San Borja Arriarán Hospital complex. Information was obtained from 30 patients with NHL and 7 with HL, with a median of 40 years. The majority of tumors were Burkitt lymphoma (47%), diffuse large cell lymphoma B-cell (37%) and NHL of T lineage (10%). There was no CNS or cavities lymphoma. Almost all patients (86.7%) with NHL were treated with CHOP chemotherapy, 57% of those receiving treatment had progression or relapse from complete remission. A rescue chemotherapy was indicated in 4 patients. 73% of patients receiving CHOP, complete 5 to 6 cycles of chemotherapy. The use of CHOP chemotherapy for the subgroup of patients with Burkitt lymphoma achieved low rates of complete remission and frequent relapse and disease progression, showing that CHOP was ineffective in improving survival, especially in high risk patients. We found statistically significant differences in survival according to IPIae (International prognostic Index age-adjusted). Non-Hodgkin lymphoma in HIV patients treated with chemotherapy protocols PAlNDA persists in our environment as a disease with a poor prognosis compared with findings in the international literature. The incorporation of new drugs of proven utility as rituximab and specific schemes chemotherapy could improve these results. The establishment of prognostic groups established by IPIae can guide clinical work for the use of chemotherapy tailored to their specific risk and optimized according to histological type.


Pharmacokinetics of oral amantadine in greyhound dogs.
This study reports the pharmacokinetics of amantadine in greyhound dogs after oral administration. Five healthy greyhound dogs were used. A single oral dose of 100 mg amantadine hydrochloride (mean dose 2.8 mg/kg as amantadine hydrochloride) was administered to nonfasted subjects. Blood samples were collected at predetermined time points from 0 to 24 h after administration, and plasma concentrations of amantadine were measured by liquid chromatography with triple quadrupole mass spectrometry. Noncompartmental pharmacokinetic analyses were performed. Amantadine was well tolerated in all dogs with no adverse effects observed. The mean (range) amantadine CMAX was 275 ng/mL (225-351 ng/mL) at 2.6 h (1-4 h) with a terminal half-life of 4.96 h (4.11-6.59 h). The results of this study can be used to design dosages to assess multidose pharmacokinetics and dosages designed to achieve targeted concentrations in order to assess the clinical effects of amantadine in a variety of conditions including chronic pain. Further studies should also assess the pharmacokinetics of amantadine in other dog breeds or using population pharmacokinetics studies including multiple dog breeds to assess potential breed-specific differences in the pharmacokinetics of amantadine in dogs.


Pictures of treatment by Gill and Schafer.
Roy Schafer and Merton Gill evoke two historically distinguished images of psychoanalytic treatment, one showing analysis elaborating life histories, and the other picturing the analyst as stirring transference embers into flame. A close examination of their implied theories of therapeutic action suggests that they mainly differ on whether allusions to the analyst are often localized in certain gestures or are always uniformly distributed throughout the patient's presentation. Because of this theoretical difference, these authors use different means to invite new experience, and they weigh differently the advantage of having a firm guide to turning-points in behavior against the advantage of maintaining an unconfinable curiosity.


All-order explicitly correlated relativistic computations for atoms and molecules.
A variational solution procedure is reported for the many-particle no-pair Dirac-Coulomb and Dirac-Coulomb-Breit Hamiltonians aiming at a parts-per-billion (ppb) convergence of the atomic and molecular energies, described within the fixed nuclei approximation. The procedure is tested for nuclear charge numbers from Z = 1 (hydrogen) to 28 (iron). Already for the lowest Z values, a significant difference is observed from leading-order Foldy-Woythusen perturbation theory, but the observed deviations are smaller than the estimated self-energy and vacuum polarization corrections.


Nanoporous nickel microspheres: synthesis and application for the electrocatalytic oxidation and determination of acyclovir.
Nickel microspheres were synthesized via a water-in-oil reverse nanoemulsion system using nickel nitrate as the nickel precursor and hydrazine hydrate as the reducing agent. The nanoemulsion was a triton X-100/cyclohexane/water ternary system. The surface morphology of the nickel microspheres was studied by scanning electron microscopy, which indicated that the microspheres had a nanoporous structure. The electrochemical behavior of the nanoporous nickel microspheres were studied in alkaline solution and were then employed to fabricate a modified carbon paste electrode in order to investigate the electrocatalytic oxidation of the drug acyclovir. The oxidation process involved, and its kinetics were investigated using cyclic voltammetry and chronoamperometry. The rate constant of the catalytic oxidation of acyclovir and the electron-transfer coefficient are reported. A sensitive, simple and time-saving amperometric procedure was developed for the analysis of acyclovir. The proposed amperometric method was also applied to determine acyclovir in tablets and topical cream.


Improvements in Systemic Therapies for Advanced Malignant Mesothelioma.
Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy associated with poor prognosis and a 5-year survival rate of 12%. Many drugs have been tested over the years with conflicting results. The aim of this review is to provide an overview of current therapies in MPM and how to best interpret the data available on these drugs. Furthermore, we focused on promising treatments under investigation, such as immunotherapy with targets different from anti-PD-1/PD-L1 inhibitors, vaccines, target therapies, and metabolism-based strategies.


[Mechanism of post-stroke reflex sympathetic dystrophy: study with needle electromyography].
To explore the mechanism of post-stroke reflex sympathetic dystrophy (RSD) patients electromyographic abnormality and confirm its clinical value. Fifty patients with first-onset stroke, aged 33 - 78, including 30 with RSD and 20 without RSD, underwent needle electromyography (EMG) to test the nerve conduction velocity (NCV) and sensory nerve conduction velocity (SCV) of bilateral median nerves, and the number and position of spontaneous EMG activity of bilateral short abductor muscles of thumb and abductor muscles little finger. The median nerve compound muscle action potential (CMAP) amplitude of the affected upper extremities of the RSD group was 8.6 mV +/- 2.9 mV, significantly lower than that of the non-RSD group (13.2 mV +/- 4.6 mV, P < 0.01). The incidence of spontaneous electrical potential of the RSD group was 100%; significantly higher than hat of the non-RSD group (65%, P < 0.001). The quantity of spontaneous EMG activity on the short abductor muscles of thumb and abductor muscles little finger was increased in the RSD group (P < 0.01). The motor nerve conduction velocity and electrophysiological presentation of sensory nerve of these 2 groups were all normal and without significant differences between them. Partial axonal degeneration occurs on the distal motor never fibers of the affected upper extremity of the RSD patients, which may be related to subsequent peripheral nerve injury after central nerve system impairment.


The uniqueness of DMAX-matrix graph invariants.
In this paper, we examine the uniqueness (discrimination power) of a newly proposed graph invariant based on the matrix DMAX defined by Randić et al. In order to do so, we use exhaustively generated graphs instead of special graph classes such as trees only. Using these graph classes allow us to generalize the findings towards complex networks as they usually do not possess any structural constraints. We obtain that the uniqueness of this newly proposed graph invariant is approximately as low as the uniqueness of the Balaban J index on exhaustively generated (general) graphs.


Cucurbitacins: specific insect attractants in Cucurbitaceae.
In vivo studies of cucurbitacins, the bitter principles present in Cucurbitaceae, indicated a quantitative relation between the concentrations of cucurbitacin in the plant and the degree of insect feeding. In vitro studies demonstrated the attractiveness of these compounds when they were separated from influences of other components of the host plants.


Mononuclear nickel(III) and nickel(II) thiolate complexes with intramolecular S-H proton interacting with both sulfur and nickel: relevance to the [NiFe]/[NiFeSe] hydrogenases.
Mononuclear, distorted square planar [Ni(II)(ER)(P(o-C(6)H(4)S)(2)(o-C(6)H(4)SH))](-) (ER = SePh (1), 2-S-C(4)H(3)S (2)) with a S-H proton directly interacting with both nickel and sulfur atoms were prepared by reaction of [Ni(CO)(SePh)(3)](-)/[Ni(CO)(2-S-C(4)H(3)S)(3)](-) and P(o-C(6)H(4)SH)(3), individually. The presence of combinations of intramolecular [Ni-S...H-SR]/[Ni...H-SR] interactions was verified in the solid state by the observation of an IR nu(SH) stretching band (2273 and 2283 cm(-)(1) (KBr) for complexes 1 and 2, individually) and (1)H NMR spectra (delta 8.079 (d) (CD(2)Cl(2)) and 8.39 (d) (C(4)D(8)O) ppm (-SH) for complexes 1 and 2, respectively) and subsequently confirmed by X-ray diffraction study. The exo-thiol proton (o-C(6)H(4)SH) in complexes 1 and 2 was identified as a D(2)O exchangeable proton from NMR and IR studies and was quantitatively removed by Lewis base Et(3)N to yield Ni(II) dimer [Ni(II)(P(o-C(6)H(4)S)(3))](2)(2)(-) (5). Instead of the ligand-based oxidation to form dinuclear Ni(II) complexes and dichalcogenide, oxidation of THF-CH(3)CN solution of complexes 1 and 2 by O(2) resulted in the formation of the mononuclear, distorted trigonal bipyramidal [Ni(III)(ER)(P(o-C(6)H(4)S)(3))](-) (ER = SePh (3), 2-S-C(4)H(3)S (4)) accompanied by byproduct H(2)O identified by (1)H NMR, respectively. The 4.2 K EPR spectra of complexes 3 and 4 exhibiting high rhombicities with three principal g values of 2.304, 2.091, and 2.0 are consonant with Ni(III) with the odd electron in the d(z)(2) orbital. Complex 3 undergoes a reversible Ni(III/II) process at E(1/2) = -0.67 V vs Ag/AgCl in MeCN.


[Lupus profundus and myelopathy].
We report a case of myelopathy during the course of lupus profundus that is unique to our knowledge. A 29-year-old woman had lupus profundus since 1999, initially associated with thrombopenia (28,000 platelets/mm3) treated with corticosteroids for 6 months. Several nodular eruptions occurred from 1999 to 2004. Antinuclear antibodies were positive at 1/320 to 1/640 and complement C4 fraction was low. While being treated with hydroxychloroquine for a recent flare-up of nodular lesions of lupus profundus, she complained of paraesthesia of the abdominal wall and of the upper and lower limbs, suggestive of a medullary lesion. MRI disclosed an image of acute myelitis at the level of the second cervical vertebra. High doses of corticosteroids were promptly administered intravenously (methylprednisolone bolus) followed by oral prednisone and hydroxychloroquine. Six months later the patient was free of neurologic or cutaneous symptoms. In the literature, systemic signs are rarely associated with lupus profundus and myelitis has never been reported. Lupus myelitis is a vascular and/or demyelinating and usually segmental lesion of the spinal cord. Neurologic symptoms are those of acute rather than chronic or recurrent transverse myelitis. The prognosis is poor with frequent and severe functional sequelae. Treatment is mainly based on high-dose systemic corticotherapy alone or combined with cyclophosphamide. Our patient responded favourably to early methylprednisolone bolus followed by oral corticosteroids and antimalarial treatment. Lupus profundus is classically of benign course with only cutaneous involvement, but it may sometimes be a sign of systemic lupus and in rare cases may be associated with severe complications.


Moringa oleifera Enhances Liver Antioxidant Status via Elevation of Antioxidant Enzymes Activity and Counteracts Paracetamol-induced Hepatotoxicity.
This study investigated the role of antioxidant enzyme system following crude hydroethanolic extract of Moringa oleifera leaves (MO) in acute paracetamol (PCM) induced hepatotoxicity. Hydroethanolic extract (80%) of MO (200 mg/kg and 800 mg/kg; p.o) was pre-administered before a single oral dose of 3 g/kg PCM intoxication to male Sprague-Dawley rats. Pre-treatment of the extract was found to have reduced lipid peroxidation level when compared to the group treated with PCM only. The level of glutathione peroxidase (GPx), glutathione-Stransferase (GST) and glutathione reductase (GR) was restored to near normal in groups that were pre-treated with MO. Histopathological studies have further confirmed the hepatoprotective activity of MO compared to group treated with PCM only. The results obtained were comparable to silymarin (200 mg/kg; p.o). The MO extract was found to have significantly protected the liver against toxicity following PCM intoxication by enhancing the level of antioxidant enzyme activity.


Expertise based skills management system to support resource allocation.
Skills Management is an essential concept of human resource management in which a skill inventory may be created for each employee and managers can assign tasks to workers based on worker's abilities. This concept is not fully practiced for two reasons: i) employee's skills are not effectively evaluated and documented, ii) tool support is deficient to manage this complex task. Ineffective skill management of an organization fizzle tasks assigned to the incompetent employees and this may lead to project failure. To fill up this gap, a survey is conducted across various software organizations to find out the best practices for the skill management and to gather requirements for skills management framework. Based on survey findings, a mathematical framework is proposed that calculates the soft and hard skills of employees automatically based on time and achievements as skill increases or decreases over time. In this framework, the Skills Calculation Engine (SCE) is developed for the managers to enhance the capacity of appropriate decisions making in assigning tasks to the rightly skilled workers. This framework is also useful for organizations as it can increase profitability as tasks are assigned to the most appropriate employees. The SCE is implemented as a Windows-based application to calculate skills, store skills in skills inventory, and assign tasks based on an employee's skills. The skills management tool is evaluated in a facilitated workshop; furthermore, a feature-wise comparison of the tool is also made with existing tools.


Rice Bran Oil: A Versatile Source for Edible and Industrial Applications.
Rice bran oil (RBO) is healthy gift generously given by nature to mankind. RBO is obtained from rice husk, a byproduct of rice milling industry and is gaining lot of importance as cooking oil due to presence of important micronutrient, gamma oryzanol. Its high smoke point is beneficial for its use for frying and deep frying of food stuff. It is popular because of balanced fatty acid profile (most ideal ratio of saturated, monounsaturated and polyunsaturated fatty acids), antioxidant capacity, and cholesterollowering abilities. Rice bran wax which is secondary by-product obtained as tank settling from RBO is used as a substitute for carnauba wax in cosmetics, confectionery, shoe creams etc. It can be also used as a source for fatty acid and fatty alcohol. The article is intended to highlight for the importance of RBO and its applications.


Synthesis and characterization of low-nuclearity lantern-type porous coordination cages.
Permanent porosity in lantern-type M4L4 paddlewheel-based cages is rare and has only been reported for naphthalene, naphthyridine, and diethynylbenzene-based linkers. This work presents the design, synthesis, and characterization of small lanterns that exhibit CO2 accessible BET surface areas in excess of 200 m2 g-1. The crystal packing and porosity of these cages can be tuned by either ligand functionalization or the choice of M2+ source used in their synthesis. Given their low nuclearity, these cages with internal M-M distances of less than 5 Å represent the lower size limit for permanently microporous coordination cages.


Stereospecific Aminative Cyclizations Triggered by Intermolecular Aza-Prilezhaev Alkene Aziridination.
Under acidic reaction conditions (TFA), deprotection of BocNR(OSO2 R) reagents triggers intermolecular aminative cyclizations of alkenes equipped with pendant nucleophiles. The processes are predicated on a sequence of stereospecific intermolecular aza-Prilezhaev aziridination followed by stereospecific SN 2-like opening by the pendant nucleophile. The method offers broad scope with respect to the nucleophile (N-, O- or C-based), alkene and cyclization mode, allowing the installation of two contiguous stereocenters under operationally simple conditions.


Wrinkling and developable cones in centrally confined sheets.
Thin sheets respond to confinement by smoothly wrinkling or by focusing stress into small, sharp regions. From engineering to biology, geology, textiles, and art, thin sheets are packed and confined in a wide variety of ways, and yet fundamental questions remain about how stresses focus and patterns form in these structures. Using experiments and molecular dynamics simulations, we probe the confinement response of circular sheets, flattened in their central region and quasistatically drawn through a ring. Wrinkles develop in the outer, free region, then are replaced by a truncated cone, which forms in an abrupt transition to stress focusing. We explore how the force associated with this event, and the number of wrinkles, depend on geometry. Additional cones sequentially pattern the sheet until axisymmetry is recovered in most geometries. The cone size is sensitive to in-plane geometry. We uncover a coarse-grained description of this geometric dependence, which diverges depending on the proximity to the asymptotic d-cone limit, where the clamp size approaches zero. This paper contributes to the characterization of general confinement of thin sheets, while broadening the understanding of the d cone, a fundamental element of stress focusing, as it appears in realistic settings.


[Evaluation of long-term results in 254 patients surgically treated by gastric resection for peptic ulcer].
The authors checked 254 patients, operated on with gastric resection according to Billroth II for peptic ulcer, at an interval ranging from 7 up to 20 years from the operation, and, on the basis of the results recorded, these patients were subdivided according to Visick's grading (15,7% in grade 1; 30,6% in grade 2; 26,4% in grade 3 S; 4,7% in grade 3 I; 14,6% in grade 4). On the whole, the remote results were considered satisfactory in 205 patients (80,7%) and unsatisfactory in 49 (19,3%): the latter represent those included in Visick's grades 3 I and 4, wherein the most serious post-resection syndromes had been ascertained; their incidence appeared absolutely higher (91,8%) in the patients subjected to gastric resection for non-complicate peptic ulcer. The Authors therefore conclude the failures of such type of operation are to be ascribed, in high percentage, to uncorrect indications thereto.


Handshake Stewardship: A Highly Effective Rounding-based Antimicrobial Optimization Service.
Implementation of an antimicrobial stewardship program is recommended as one solution to combat increasing antimicrobial resistance. Most antimicrobial stewardship programs use preauthorization or restrictive strategies recommended in national guidelines. We describe a unique, rounding-based strategy, handshake stewardship. Handshake stewardship is distinguished by: (1) lack of restriction and preauthorization, (2) review of all prescribed antimicrobials and (3) a rounding-based, in-person approach to feedback by a pharmacist-physician team. We retrospectively measured antimicrobial use hospital-wide and by unit during preimplementation, planning, and postimplementation phases of the handshake stewardship approach to determine the efficacy of this strategy in decreasing use in a freestanding children's hospital. All antimicrobials prescribed on the inpatient services between October 2010 and September 2014 were included in the review. Monthly antimicrobial use (hospital-wide and by unit) was measured in days of therapy per 1000 patient days (DOT/1000 PD). Overall antimicrobial use decreased by 10.9% during the 4 years of the analysis (942 to 839 DOT/1000 PD, P < 0.01), with an impact of 10.3% on antibacterials (750 to 673 DOT/1000 PD, P < 0.01). Vancomycin use decreased by 25.7% (105 to 78 DOT/1000 PD, P < 0.01). Meropenem use decreased by 22.2% (45 to 35 DOT/1000 PD, P = 0.04) without a compensatory increase of other antipseudomonal agents. Decreased usage was observed both hospital-wide and on individual units for most agents. The handshake stewardship approach is an effective strategy for an antimicrobial stewardship program, as demonstrated by the widespread and significant decrease in antimicrobial use after implementation.


Adaptations of hepatic lipid metabolism and mitochondria in dairy cows with mild fatty liver.
The inevitable deficiency in nutrients and energy at the onset of lactation requires an optimal adaptation of the hepatic metabolism to overcome metabolic stress. Fatty liver is one of the main health disorders after parturition. Therefore, to investigate changes in hepatic lipid metabolic status and mitochondria in dairy cows with mild fatty liver, liver and blood samples were collected from healthy cows (n = 15) and cows with mild fatty liver (n = 15). To determine the effects of palmitic acids (PA), one of the major component of fatty acids, on lipid metabolism and mitochondria in vitro, calf hepatocytes were isolated from healthy calves and treated with various concentrations of PA (0, 50, 100, and 200 μM). Dairy cows with mild fatty liver displayed hepatic lipid accumulation. The protein levels of sterol regulatory element-binding protein 1c (SREBP-1c) and peroxisome proliferator-activated receptor-α (PPARα) and mRNA levels of acetyl CoA carboxylase 1 (ACC1), fatty acid synthase (FAS), acyl-CoA oxidase (ACO), and carnitine palmitoyltransferase 1A (CPT1A) were significantly higher in dairy cows with mild fatty liver than in control cows. The hepatic mitochondrial DNA content, mRNA levels of oxidative phosphorylation complexes I to V (CO 1-V), protein levels of cytochrome c oxidase subunit IV (COX IV), voltage dependent anion channel 1 (VDAC1), peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α) and nuclear respiratory factor 1 (NRF1), and adenosine triphosphate (ATP) content were all markedly increased in the liver of dairy cows with mild fatty liver compared with healthy cows. The PA treatment significantly increased lipid accumulation; protein levels of SREBP-1c and PPARα; and mRNA levels of ACC1, FAS, ACO, and CPT1A in calf hepatocytes. Moreover, the mitochondrial DNA content, mRNA levels of CO 1-V, protein levels of COX IV, VDAC1, PGC-1α, NRF1, mitochondrial transcription factor A, and ATP content were significantly increased in PA-treated hepatocytes compared with control hepatocytes. The protein level of mitofusin-2 was significantly decreased in PA-treated groups. In conclusion, lipid synthesis and oxidation, number of mitochondria, and ATP production were increased in the liver of dairy cows with mild fatty liver and PA-treated calf hepatocytes. These changes in hepatic mitochondria and lipid metabolism may be the adaptive mechanism of dairy cows with mild fatty liver.


A model based algorithm for perfusion estimation in interventional C-arm CT systems.
Interventional C-arm CT imaging, today, plays an important role in the diagnosis and treatment of patients. The main part of the 3D imaging techniques, currently used in interventions, are morphological imaging techniques. So far, the ability for functional or perfusion imaging is limited, e.g., only static cerebral blood volume measurement [A. S. Ahmed, Y. Deuerling-Zheng, C. M. Strother, K. A. Pulfer, M. Zellerhoff, T. Redel, K. Royalty, D. Consigny, M. J. Lindstrom, and D. B. Niemann, "Impact of intra-arterial injection parameters on arterial, capillary, and venous time-concentration curves in a ca480 nine model," AJNR Am. J. Neuroradiol. 30, 1337-1341 (2009)] is available. The sample rate of current C-arm CT systems is not fast enough yet to measure dynamic parameters like cerebral blood flow using standard Feldkamp reconstruction. The authors propose a reconstruction algorithm that models the time-dependent attenuation values of each voxel using a gamma-variate function. The method can be divided into a segmentation-based initialization and an iterative optimization step. For the initialization, a threshold-based segmentation of vessel, tissue, and nondynamic structures (e.g., bone and air) is performed on the filtered backprojection (FBP) reconstructions. For each of these regions, homogeneous time-attenuation curves are estimated to initialize all the voxels within the region. The scaling-factor is then adjusted for each voxel using the attenuation values of the static reconstructions. The second part of the algorithm is an iterative optimization of the gamma-variate parameters of each voxel, based on a simultaneous algebraic reconstruction technique. Within each iteration, a Levenberg optimization is applied to minimize the backprojected errors. The algorithm is quantitatively evaluated with simulated forward projections as well as real C-arm CT projection data. In the phantom experiments, penumbra and infarct core could be segmented with an adjusted Rand index of up to 0.95 for a noise level of 10(5) photons. Perfusion CT data sets from three patients were used to compare the iterative reconstruction approach to the interpolated FBP reconstruction using different sweep times. In their experiments, a sweep time of 4 s using iterative reconstruction would be equivalent to that using interpolated FBP with a sweep time of around 1 s. The reconstruction results of the animal study are compared to a perfusion CT acquisition, sampled with 1 frame per second. A correlation coefficient of 0.75 between the original and the reconstructed CBF-maps could be reached with the iterative approach compared to 0.56 using the interpolated FBP reconstruction. In their experiments, the quality of dynamic perfusion measurements was improved using the proposed reconstruction algorithm compared to static reconstruction followed by interpolation. It could be used to increase the temporal resolution of current C-arm CT system without hardware modification to make them feasible for dynamic perfusion measurement. Furthermore, radiation dose could be reduced using their method to increase temporal resolution than using static reconstruction with a higher sampling frequency.


Scutellarin Suppresses NLRP3 Inflammasome Activation in Macrophages and Protects Mice against Bacterial Sepsis.
The NLRP3 inflammasome plays a critical role in mediating the innate immune defense against pathogenic infections, but aberrant activation of NLRP3 inflammasome has been linked to a variety of inflammatory diseases. Thus targeting the NLRP3 inflammasome represents a promising therapeutic for the treatment of such diseases. Scutellarin is a flavonoid isolated from Erigeron breviscapus (Vant.) Hand.-Mazz. and has been reported to exhibit potent anti-inflammatory activities, but the underlying mechanism is only partly understood. In this study, we aimed to investigate whether scutellarin could affect the activation of NLRP3 inflammasome in macrophages. The results showed that scutellarin dose-dependently reduced caspase-1 activation and decreased mature interleukin-1β (IL-1β) release in lipopolysaccharide (LPS)-primed macrophages upon ATP or nigericin stimulation, indicating that scutellarin inhibited NLRP3 inflammasome activation in macrophages. Consistent with this, scutellarin also suppressed pyroptotic cell death in LPS-primed macrophages treated with ATP or nigericin. ATP or nigericin-induced ASC speck formation and its oligomerization were blocked by scutellarin pre-treatment. Intriguingly, scutellarin augmented PKA-specific phosphorylation of NLRP3 in LPS-primed macrophages, which was completely blocked by selective PKA inhibitor H89, suggesting that PKA signaling had been involved in the action of scutellarin to suppress NLRP3 inflammasome activation. Supporting this, the inhibitory effect of scutellarin on NLRP3 inflammasome activation was completely counteracted by H89 or adenyl cyclase inhibitor MDL12330A. As NLRP3-dependent release of IL-1β has a critical role in sepsis, the in vivo activity of scutellarin was assayed in a mouse model of bacterial sepsis, which was established by intraperitoneally injection of a lethal dose of viable Escherichia coli. Oral administration of scutellarin significantly improved the survival of mice with bacterial sepsis. In line with this, scutellarin treatment significantly reduced serum IL-1β levels and attenuated the infiltration of inflammatory cells in the liver of E. coli-infected mice. These data indicated that scutellarin suppressed NLRP3 inflammasome activation in macrophages by augmenting PKA signaling, highlighting its potential therapeutic application for treating NLRP3-related inflammatory diseases.


Quality of life and physical activity in a sample of Brazilian older adults.
To investigate the association between physical activity and quality of life in a sample of Brazilian older adults. The Portuguese version of the World Health Organization Quality of Life Instrument-Older Adults Module and International Physical Activity Questionnaire was administered to 1,204 subjects (645 women and 559 men) aged ≥ 60 years. Older adults of both genders who reported to be more physically active attributed higher scores to the sensory ability, autonomy, and intimacy domains, in addition to presenting significantly higher overall quality of life, irrespectively of age, marital status, educational level, and socioeconomic status. Specifically in women, the scores obtained for the social participation domain were significantly higher in the strata of active and very active subjects when compared to sedentary subjects. The results indicate that increases in the levels of physical activity can contribute to improvements in quality of life of older adults.


Long-term lamotrigine plus lithium for bipolar disorder: One year outcome.
To obtain pilot data in an observational setting on the use of lamotrigine plus lithium in the long-term treatment of patients with bipolar disorder, 87% of whom had failed to respond to at least one previous mood stabilizer. Charts of 21 patients (11 females, 10 males, mean age 43.2 years) treated with the combination of lithium and lamotrigine were reviewed retrospectively for treatment response using the Clinical Global Impression-Bipolar Disorder-Improvement scale, divided into benefit for acute depressive symptoms, acute manic symptoms, and overall illness (including prophylaxis of mood episodes). Of the 21 patients, 76% were diagnosed with bipolar I disorder, and depressive symptoms were the most common acute indication for treatment (52%). Mean doses of lithium and lamotrigine were 963 mg/day and 179 mg/day, respectively, used for a mean of 55.7 weeks. Acute antidepressant benefit was observed in 48% of patients, acute anti-manic benefit in 14%, and overall prophylactic benefit in 29%. Side effects were observed in 38%, with cognitive problems most common (29%). 48% discontinued combination therapy, mainly due to lack of efficacy (19%) or activation of manic-like symptoms (19%). Among a group of largely treatment-resistant bipolar patients, the combination of lithium and lamotrigine appeared effective for acute depressive symptoms in about half of the patients, but acute anti-manic and long-term prophylactic efficacy appeared less robust.


A software program combining sequence motif searches with keywords for finding repeats containing DNA sequences.
One of the most interesting features of genomes (both coding and non-coding regions) is the presence of relatively short tandemly repeated DNA sequences known as tandem repeats (TRs). We developed a new PC-based stand-alone software analysis program, combining sequence motif searches with keywords such as organs, tissues, cell lines or development stages for finding exact, inexact and compound, TRs. Tandem Repeats Analyzer 1.5 (TRA) has several advanced repeat search parameters/options over other repeat finder programs as it does not only accept GenBank, FASTA and expressed sequence tag (EST) sequence files but also does analysis of multifiles with multisequences. Advanced user-defined parameters/options let the researchers use different motif lengths search criteria for varying motif lengths simultaneously. The outputs show statistical results to be evaluated by the user. The discovery of TRs in ESTs could be useful for both gene mapping and association studies and discovering TRs located in coding regions of important genes that are expressed under various conditions of environment, stress, organ, tissue and development stage. In this paper, we demonstrated applications of TRA using 175 899 ESTs sequences for three Arabidopsis spp. downloaded from GenBank. The EST-SSRs/ESTs ratios were found 43.1%, 15.3% and 2.34% in A.lyrata, A.thaliana and A.halleri, respectively. Analysis revealed that organs, tissues and development stages possessed different amounts of repeats and repeat compositions. This indicated that the distribution of TRs among the tissues or organs may not be random differing from the untranscribed repeats found in genomes. The program can be obtained free by anonymous FTP from ftp.akdeniz.edu.tr/Araclar/TRA.