Quantitative determination of the macrolide antibiotics erythromycin, roxithromycin, azithromycin and clarithromycin in human serum by high-performance liquid chromatography using pre-column derivatization with 9-fluorenylmethyloxycarbonyl chloride and fluorescence detection.
A validated, highly sensitive and precise high-performance liquid chromatographic (HPLC) method for the determination of the macrolides erythromycin, azithromycin, clarithromycin and roxithromycin in human serum is described. A diethyl ether extract, obtained from serum using a saturated sodium carbonate solution, was treated with 9-fluorenylmethyl-oxycarbonyl chloride (FMOC-Cl) for 40 min at 40 degrees C and chromatographed on a base-deactivated octadecyl column, maintained at 50 degrees C during elution, using an eluent composed of acetonitrile-hydrogenphosphate buffer, pH 7.5, with 0.125% triethylamine (3:2, v/v). Fluorescence detection was used at an excitation wavelength of 255 nm and an emission wavelength of 315 nm. Erythromycin, clarithromycin, roxithromycin and azithromycin were found to have retention times of 8.8, 15.7, 17.1 and 20.7 min, respectively. Recoveries ranging from 93 to 104% were found with reproducibility coefficients of variation of 1.1-5%. Mean correlation coefficients of 0.9997, 0.9998, 0.9996 and 0.9994 were found for the linear calibration curves (n = 2) of erythromycin (0.320-16.1 mg/l), roxithromycin (3.24-19.4 mg/l), clarithromycin (0.190-19.4 mg/l) and azithromycin (0.0988-4.94 mg/l), respectively.


Size effect of Pt nanoparticles in acid-assisted soot oxidation in the presence of NO.
Pt/Al2O3 catalysts with mean Pt particle size ranged from 2.7 to 7.1 nm were synthesized by chemical reduction method, and the sulfated counterparts were prepared by impregnation of sulfuric acid. The turnover frequency of platinum for soot oxidation under loose contact conditions in a feed flow containing NO and O2 are positively correlated with the size of platinum. The sulfated Pt/Al2O3 exhibits higher catalytic activity for soot oxidation in the presence of NO despite their reduced ability for NO2 production. Such a contradiction is more significant for those catalysts with smaller platinum particles. Herein, the catalysts were characterized by X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET), transmission electron microscopy (TEM), inductive coupled plasma (ICP) emission spectrometry, CO chemisorption, thermogravimetric analysis (TGA), NH3 temperature-programmed desorption (NH3-TPD), NO temperature-programmed oxidation (TPO) and NOx temperature-programmed desorption (TPD). Possible effect of Pt particle size for the catalytic oxidation of soot in the presence of NO was presented based primarily on the promoted NO2 transfer efficiency onto the soot pushed by the acidic catalysts.


The Association Between Anxiety Symptoms and Sleep in School-Aged Children: A Combined Insight From the Children's Sleep Habits Questionnaire and Actigraphy.
The current study assessed the association between anxiety symptoms and sleep in 90 school-aged children, aged 6-12 years (Mage = 108 months, 52.2% male). The Children's Sleep Habits Questionnaire (CSHQ) and 14 nights of actigraphy were used to assess sleep. Anxiety was assessed using the Spence Children's Anxiety Scale (SCAS). A significant association was found between parent-reported anxiety symptoms and current sleep problems (i.e., CSHQ total scores ≥ 41). An examination of SCAS subscales identified a specific association between generalized anxiety disorder (GAD) symptoms and increased parental sleep concerns, including sleep onset delay, sleep duration, and daytime sleepiness. Regarding actigraphy, whilst anxiety was not associated with average sleep variables, a relationship was identified between anxiety and the night-to-night variability of actigraphy-derived sleep schedules.


[Expression of FHIT gene protein in laryngeal carcinoma].
To investigate the role and clinical significance of the expression of FHIT gene in development and progression of laryngeal squamous cell carcinoma(LSCC). The expression FHIT protein was detected by immunohistochemistry method in the 52 cases with LSCC and 23 cases of adjacent cancer tissues and 10 cases of laryngeal normal mucosa. The expression of FHIT was analyzed in LSCC with different clinicopathological parameters. The expression of FHIT in normal tissues (90.0%) and adjacent tissues (78.3%) was obvious higher than that in LSCC (46.2%), which had statistical significant difference (P < 0.01). There was a positive correlation between FHIT expression and TNM staging, lymph node metastasis; but not pathological grade. The loss of FHIT expression may be correlated with the development and progression of laryngeal carcinoma. FHIT may be an important tumor suppressor gene in LSCC.


Decline in Distribution and Abundance: Urban Hedgehogs under Pressure.
Increasing urbanization and densification are two of the largest global threats to biodiversity. However, certain species thrive in urban spaces. Hedgehogs Erinaceus europaeus have been found in higher densities in green areas of settlements as compared to rural spaces. With recent studies pointing to dramatically declining hedgehog numbers in rural areas, we pose the question: how do hedgehogs fare in urban spaces, and do these spaces act as refuges? In this study, recent (2016-2018) and past (1992) hedgehog abundance and distribution were compared across the city of Zurich, Switzerland using citizen science methods, including: footprint tunnels, capture-mark recapture, and incidental sightings. Our analyses revealed consistent negative trends: Overall hedgehog distribution decreased by 17.6% ± 4.7%, whereas abundance declined by 40.6% (mean abundance 32 vs. 19 hedgehogs/km2, in past and recent time, respectively), with one study plot even showing a 91% decline in this period (78 vs. 7 hedgehogs/km2, respectively). We discuss possible causes of this rapid decline: increased urban densification, reduction of insect biomass, and pesticide use, as well as the role of increasing populations of badgers (a hedgehog predator) and parasites or diseases. Our results suggest that hedgehogs are now under increasing pressure not only in rural but also in urban areas, their former refuges.


Solubilization and characterization of phosphoprotein phosphatase(s) from bovine corpus-luteum plasma membranes.
Plasma membrane fractions I and II isolated from bovine corpus luteum contain phosphoprotein phosphatases. Enzyme activities associated with both membrane fractions showed pH optima in the neutral range and were most active with phosphoprotamine as the exogenous substrate. The enzyme activity was partially inhibited by Co2+, Zn2+ and Fe2+. Dithioerythritol, glutathione (reduced) and 2-mercaptoethanol stimulated the enzyme activity, whereas N-ethylmaleimide and N-phenylmaleimide were inhibitory. Similarly, various cyclic nucleotides and nuclsoside triphosphates also inhibited phosphoprotein phosphatase activities. The phosphatase activity was also observed with endogenous phosphorylated membrane proteins as substrate. The endogenous phosphorylation of membranes was rapid and attained a maximal level after 15--20 min of incubation. Initially endogenous dephosphorylation was also very rapid, but did not reach completion. In addition to phosphoprotein phosphatase, membrane preparations also possessed very active cyclic-AMP-dependent protein kinase activity. Phosphoprotein phosphatase activity from plasma membranes was solubilized by ionic and nonionic detergents. Optimal solubilization was achieved with 0.1% sodium deoxycholate. Sucrose density gradient centrifugation of deoxycholate-solubilized fraction I and fraction II membranes resolved phosphoprotein phosphatase activity into two species with apparent sedimentation coefficients of 6.7 S (Mr 130000) and 4.8 S (Mr 90000). Cyclic-AMPstimulated protein kinase activity sedimented as a broad peak with a sedimentation coefficient of 5.5 S (Mr 110000).


Determinants of pneumonia among under-five children at Hiwot Fana specialized hospital, Eastern Ethiopia: unmatched case-control study.
Globally, pneumonia is a serious public health issue. Clear evidence is necessary for the early detection and treatment of pneumonia's causes. Yet, there is limited data on this issue in the current study area. Thus, this study aimed to pinpoint the determinants of pneumonia among under-five children at Hiwot Fana Specialized Hospital, Eastern Ethiopia. A hospital-based unmatched case-control study was conducted among a sample of 348 (116 cases and 232 controls) children at Hiwot Fana Specialized Hospital from October 1 to November 30, 2022. A consecutive sampling technique was employed, and data were collected with a pre-tested interviewer-administered questionnaire. The data was entered into Epi-Data version 3.1 and analyzed using SPSS version 25 software. Bivariate and multivariate binary logistic regression analyses were fitted. Variables with a 95% confidence interval having a p-value < 0.05 were considered statistically significant. An overall total of 347 (115 cases and 232 controls) among under-five children was included in this study. Factors such as hand washing before child feeding [AOR: 3.11 (1.74-5.57)], birth to 6 months breastfeeding [AOR: 2.76 (1.35-5.25)], zinc supplementation [AOR: 2.5 (1.33-4.40)], diarrhea in the last 2 weeks [AOR: 4.7 (2.64-8.33)], and Upper Respiratory Tract Infections in the last 2 weeks [AOR: 5.46 (3.21-10.92)] were found to be determinants of pneumonia. This study pointed out that the under-five pneumonia was relatively large. Factors such as hand washing before child feeding, birth to 6 months of breastfeeding, zinc supplementation of the child, diarrhea in the last 2 weeks, and Upper Respiratory Tract Infections in the last 2 weeks were determinants of under-five pneumonia. In this study, the primary risk factors for pneumonia may be preventable with no or minimal cost. Therefore, we advise suitable and sufficient health education addressing the prevention and management of pneumonia.


The involvement of organic acids in soil fertility, plant health and environment sustainability.
Increasing demand for safe food by an ever-growing human population emphasizes the urgency for increasing crop yields and reducing the losses caused by abiotic and biotic stresses; a partial solution to this problem is to develop a better understanding of plant-microbe interactions. Plant roots continuously release a wide range of compounds including organic acids in root exudates. These root exudates stimulate growth of specific microbial communities in the rhizosphere, which affect complex biological and physico-chemical interactions occurring between plant roots and the surrounding soil environment. In addition, organic acids are also released by different microbes and during decomposition of organic matter and plant residues in the soil. Interestingly, the available organic acids in the rhizosphere play crucial roles in various physio-chemical processes including the chemoattraction of microbes (both beneficial and pathogenic), mineralization and solubilization of complex minerals (P, K and Zn), biocontrol of phytopathogens, induction of systemic resistance, biogas formation, mitigation of abiotic stresses and, detoxification of metals and residual pesticides. Thus, organic acids play a significant role in the sustainable management of the soil ecosystem and in environmental sustainability. This review discusses the role of organic acids in the stimulation or enrichment of specific root-associated microbial communities and their effect on plant-microbe interactions at the root surface. In addition, the potential for root microbiome modification to enhance nutrient cycling and nutrient acquisition, and in amelioration of environmental stresses for increasing food production is discussed.


The Role of Immunomodulator Betaleukin in Recovery of Hepatocytic Ploidy Profile in Delayed Terms after Irradiation.
We studied the radioprotective effect of betaleukin administered to (CBA×C57Bl/6)F1 mice in single doses of 50 and 3 μg/kg 2 and 22 h, respectively, prior to long-term (21 h) whole-body low-intensity (10 mGy/min) γ-radiation (137Сs; total dose 12.65 Gy). Hepatocyte ploidy, a biomarker of metabolic disorders of the liver, was evaluated, and nuclearity and ploidy indices were calculated. In 10 months after irradiation, a significant decrease in the ploidy index was revealed in the group of irradiated mice, while in animal receiving 3 or 50 μg/kg betaleukin, this parameter did not differ and even surpassed the control level, respectively. Thus, in vivo assessment of hepatocytic ploidy profile in mice revealed negative delayed effects of γ-irradiation in a dose of 12.65 Gy and a protective effect a single injection of immunomodulator betaleukin.


Clinical significance of prognostic nutritional index (PNI)-monocyte-to-lymphocyte ratio (MLR)-platelet (PLT) score on postoperative outcomes in non-metastatic clear cell renal cell carcinoma.
Prognositic nutritional index (PNI), monocyte-to-lymphocyte ratio (MLR) and platelet (PLT) are associated with tumor survival in many human malignancies. Whereas, no study combined PNI-MLR-PLT score and indicated its predictive significance on the prognosis of patients with non-metastatic clear cell renal cell carcinoma (ccRCC). In this study, we retrospectively collected the clinicopathological characteristics and prognostic data from 164 cases of non-metastatic ccRCC and aimed to determine the clinical significance of PNI-MLR-PLT score on patients' outcomes after surgery. The optimal cut-off values of PNI (PNI > 47.40 vs PNI < 47.40), MLR (MLR > 0.31 vs MLR < 0.31) and PLT (PLT > 245 vs PLT < 245) were identified with relative operating characteristic (ROC) curve analysis. The PNI-MLR-PLT score system was established by the value of three indexes, each indication was assigned a score of 0 or 1. Overall survival (OS) and metastasis-free survival (MFS) were analyzed using Kaplan-Meier estimate and Cox regression models. The mean follow-up period was 85.67 months. Eight (5.0%) patients died, 4 (2.0%) relapsed, and 7 (4.0%) developed metastasis after surgery. The 3-year OS and MFS rates were 98.2% and 97.6%, and the 5-year OS and MFS rates were both 90.2%. Our results suggested that PNI-MLR-PLT score negatively correlated with pathological T stage and tumor grade. Survival outcomes revealed that lower PNI-MLR-PLT score is associated with inferior OS (P < 0.001) and MFS (P < 0.001) after surgery. Subgroup analysis regarding pathological T stage, tumor grade and surgical modalities obtained consistent results. univariable and multivariable Cox analysis showed that high PNI-MLR-PLT score was the independent protective factor of tumor survival in non-metastatic ccRCC patients. Our data suggested that PNI-MLR-PLT score could serve as a promising independent prognostic factor in patients with non-metastatic ccRCC.


Ascorbic Acid Derivative 2-O-β-d-Glucopyranosyl-l-Ascorbic Acid from the Fruit of Lycium barbarum Modulates Microbiota in the Small Intestine and Colon and Exerts an Immunomodulatory Effect on Cyclophosphamide-Treated BALB/c Mice.
2-O-β-d-Glucopyranosyl-l-ascorbic acid (AA-2βG) is a natural and stable ascorbic acid derivative isolated from the fruits of Lycium barbarum. In our present study, cyclophosphamide (Cy) was used to make BALB/c mice immunosuppressive and AA-2βG was used to intervene immunosuppressive mice. It was found that Cy treatment resulted in a series of changes on basic immune indexes including a decrease of thymus and spleen indexes and levels of pro-inflammatory cytokines and destruction of leucocyte proportion balance, accompanied with weight loss, reduction in colon length, and changes of hepatic function markers. However, all these changes were reversed in varying degrees by AA-2βG intervention. Notably, AA-2βG could significantly change both mouse colonic and small-intestinal microbiota. The key responsive taxa found in a mouse colon were Muribaculaceae, Ruminococcaceae, Oscillibacter, Rikenella, Helicobacter, Negativibacillus, Alistipes, and Roseburia, and the key responsive taxa found in a mouse small intestine were Muribaculaceae, Anaerotruncus, and Paenibacillus. The results demonstrated that AA-2βG could modulate microbiota in the small intestine and colon and exert an immunomodulatory effect. Further studies should focus on the degradation pathways of AA-2βG and the interaction between AA-2βG and Muribaculaceae.


Maintenance repetitive transcranial magnetic stimulation (rTMS) therapy for treatment-resistant depression: a study protocol of a multisite, prospective, non-randomized longitudinal study.
Repetitive transcranial magnetic stimulation (rTMS) is a widely used treatment for major depressive disorder (MDD), and its effectiveness in preventing relapse/recurrence of MDD has been explored. Although few small sample controlled studies exist, the protocols of maintenance rTMS therapy were heterogeneous and evidence of its effectiveness is not sufficient. Thus, this study aims to evaluate whether maintenance rTMS is effective in maintaining the treatment response in patients with MDD with a large sample size and feasible study design. In this multicenter open-labelled parallel-group trial we plan to recruit 300 patients with MDD who have responded or remitted to acute rTMS therapy. Participants would be classified into two groups according to their preference; the maintenance rTMS and pharmacotherapy group, and the pharmacotherapy only group. The protocol of maintenance rTMS therapy is once a week for the first six months and once biweekly for the second six months. The primary outcome is the relapse/recurrence rates during 12 months following enrollment. Other measures of depressive symptoms and recurrence/relapse rates at different time points are the secondary outcomes. The primary analysis is the between-group comparison adjusted for background factors using a logistic regression model. We will perform the group comparison with inverse probability of treatment weighting as the sensitivity analysis to ensure the comparability of the two groups. We hypothesize that maintenance rTMS therapy could be an effective and safe treatment for preventing depressive relapse/recurrence. Considering the limitation of potential bias owing to the study design, we plan to use statistical approaches and external data to avoid overestimation of the efficacy. Japan Registry of Clinical Trials, ID: jRCT1032220048 . Registered 1 May 2022.


RNA cleavage efficiency and catalytic turnover of an oligonucleotide-two copper complexes conjugate.
We synthesized a 2'-O-methyloligonucleotide with two terpyridine-Cu(II) complexes in the central part, and found that this antisense agent cleaves an RNA oligomer more efficiently than an analogous agent with one Cu(II) complex. Determination of the pH dependence of the activity revealed the existence of an optimum pH for the two complexes-agent, which may be a result of the cooperative action of the complexes. In addition, we demonstrated that the novel agent catalytically cleaved an excess of the RNA substrate.


Alkaline phosphatase phenotypes in tumour and non-tumour cell lines: not an invariable marker for neoplastic transformation.
The cytochemical localisation and presumed isoenzyme type (based on selective inhibition experiments) of alkaline phosphatase in 5 cell lines derived frrom normal human, rat, mouse and hamster tissues, 6 human lymphoblastoid lines and 6 human and mouse tumour-derived cell lines are described. Enzyme activity varied between the cell lines. An isoenzyme inhibited by L-phenylalanine was present in 3 normal lines, 3 lymphoblastoid lines and 2 tumour lines. The presence of this isoenzyme cannot be used as a marker of neoplastic transformation.


Utilization of Coronary Artery to Aorta for the Early Detection of Kawasaki Disease.
Timely diagnosis of coronary involvement is paramount in Kawasaki disease (KD) as it can be associated with long-term morbidity. However, echocardiographic measurements of coronary artery dilation in KD are inconsistent and not proficient for all abnormal arteries. The purpose of this study was to investigate more valuable indices and determine their sensitivity and specificity for early diagnosis of coronary involvement in KD. We performed this retrospective study in 218 children. All patients underwent laboratory and echocardiographic evaluations upon admission. We measured the size of the left main coronary artery (LMA), left anterior descending coronary artery (LAD), right coronary artery (RCA), and aorta (Ao), and calculated the LMA/Ao, LAD/Ao, and RCA/Ao ratios. We also calculated the cut-off values of each index using receiver operating characteristic curves. LMA, LAD, and RCA measurements did not correlate with white blood cell count, platelet count, erythrocyte sedimentation rate, C-reactive protein level, or brain natriuretic peptide level. The LMA measurement was associated with hemoglobin, hematocrit, and iron saturation. LAD/Ao was correlated with white blood cell and platelet counts (P < 0.05), whereas RCA/Ao was correlated with ferritin level (P < 0.05). The cut-off value of LMA/Ao was 0.2, with a sensitivity of 85% and specificity of 70%. Individual coronary artery/Ao ratios might provide helpful insight for detection of coronary abnormality in KD in the acute phase. Further investigation is essential to clarify prompt early diagnosis of coronary involvement in KD.


Genetic polymorphism of both 29 Y-STRs and 213 Y-SNPs in Han populations from Shandong Province, China.
Genetic markers on the Y chromosome, including short tandem repeats (Y-STRs) and single nucleotide polymorphisms (Y-SNPs), are used widely in forensic genetics. Both Y-STR-based haplotypes and Y-SNP-based haplogroups provide information on a population's genetic structure, which is useful for the identification of individuals. However, there are few studies on these two types of genetic markers in the various Chinese populations. In this study, 284 Han individuals from four prefecture-level cities in Shandong Province (Binzhou, Dezhou, Heze, and Weihai) were genotyped by 29 Y-STRs (from our previous study) and 213 Y-SNPs (self-designed for the Haplogroup O2 Y-SNP panel). Haplogroup O was the most predominant among the four cities. The highest haplogroup diversity (0.9745) was observed in the Heze population, with a discrimination capacity (DC) value of 0.5625. The haplotype diversity and DC values of the Binzhou and Heze populations were 1.0000. Furthermore, genetic differences were observed between the coastal and inland cities; the results of their statistical analysis are presented herein.


Increased translatable mRNA and decreased lipogenesis are responsible for the augmented secretion of lipid-deficient apolipoprotein E by hepatocytes from fasted rats.
We examined the mechanism through which fasting selectively increases the secretion of apoE while it decreases the secretion of all lipoprotein lipids (Davis, R. A., Boogaerts, J. R., Borchardt, R. A., Malone-McNeal, M., and Archambault-Schexnayder, J. (1985) J. Biol. Chem. 260, 14137-14144). Livers were obtained from rats that were fed chow plus drinking water (control) and drinking water only (fasted) for three days. Livers were extracted for both total and poly(A) RNA. Using full length, nick-translated 32P-labeled cDNA probes for both apoE and beta-actin, the relative abundance was determined by slot blot hybridization assays. There was 2-fold more apoE mRNA in the livers of fasted rats. Furthermore, translation of poly(A) RNA using a reticulocyte lysate showed a similar 2.3-fold increase in the synthesis of immunoprecipitable [35S]methionine-labeled apoE. The 2-fold increase in translatable apoE mRNA correlates with a similar increase in apoE secretion. We also characterized the form of apoE secreted by hepatocytes from fasted cells. Cells were labeled with [35S]methionine, and the medium was separated by agarose 0.5m column chromatography. The majority of the apoE secreted cells from both control and fasted rats eluted in fractions that contained no detectable lipid. Furthermore, almost all of the increased apoE secreted by fasted cells was in these lipid-deficient fractions. The isoform distribution of apoE secreted by cells from both groups consisted of six major apoE isoforms. Consistent with previous results, treatment with neuraminidase transformed the acidic forms into the three most basic, suggesting that the three most acidic isoforms contain varying amounts of sialic acid. The isoform pattern of apoE secreted by cells from fasted rats was significantly enriched in two acidic isoforms, while it was significantly decreased in the major basic isoform. Moreover, when oleic acid (1 mM) was added to the culture medium to stimulate lipogenesis, the amount of apoE secreted with lipid increased as did the more basic isoforms. These data suggest that the secretion of lipid-deficient apoE by cells from fasted rats is the result of increased mRNA and a concomitant reduction in lipogenesis. Furthermore, the parallel shift of both the amount of apoE secreted associated with lipid as well as its isoform pattern to a more basic one by oleic acid suggests that the lipid availability plays a role in determining the lipid complement and sialic acid content of apoE secreted by the hepatocyte.


Classification of Parkinson's disease and essential tremor based on balance and gait characteristics from wearable motion sensors via machine learning techniques: a data-driven approach.
Parkinson's disease (PD) and essential tremor (ET) are movement disorders that can have similar clinical characteristics including tremor and gait difficulty. These disorders can be misdiagnosed leading to delay in appropriate treatment. The aim of the study was to determine whether balance and gait variables obtained with wearable inertial motion sensors can be utilized to differentiate between PD and ET using machine learning. Additionally, we compared classification performances of several machine learning models. This retrospective study included balance and gait variables collected during the instrumented stand and walk test from people with PD (n = 524) and with ET (n = 43). Performance of several machine learning techniques including neural networks, support vector machine, k-nearest neighbor, decision tree, random forest, and gradient boosting, were compared with a dummy model or logistic regression using F1-scores. Machine learning models classified PD and ET based on balance and gait characteristics better than the dummy model (F1-score = 0.48) or logistic regression (F1-score = 0.53). The highest F1-score was 0.61 of neural network, followed by 0.59 of gradient boosting, 0.56 of random forest, 0.55 of support vector machine, 0.53 of decision tree, and 0.49 of k-nearest neighbor. This study demonstrated the utility of machine learning models to classify different movement disorders based on balance and gait characteristics collected from wearable sensors. Future studies using a well-balanced data set are needed to confirm the potential clinical utility of machine learning models to discern between PD and ET.


Preparative protein concentration from biofluids by epitachophoresis.
With increasing demands on protein analyses in complex biological matrices, the insistence on developing new sample preparation techniques is rising. Recently, we introduced a new displacement electrophoresis technique (epitachophoresis) and instrumentation for preparative concentration and cleaning of DNA samples. This work describes the possibility of applying this device to protein samples. We have developed a method for the epitachophoretic concentration of proteins in a cationic mode and tested it by concentrating and collecting the protein zones from complex biological matrices (urine and growth medium). Under optimized conditions, we have obtained recoveries up to 99%. Furthermore, the applicability of the developed method was proven by concentrating and collecting the cytochrome c zone from a HeLa cell line growth medium, where the protein cytochrome c was released during cell apoptosis.


Experimental spondyloarthropathies: animal models of ankylosing spondylitis.
Spondyloarthropathies (SpAs), including ankylosing spondylitis, are chronic inflammatory diseases of the axial skeleton. Genomic scans of SpA families revealed the overwhelming complexity of the disease, which appears to be under the control of over 20 chromosome loci, including the major SpA gene HLA-B27 within class I of the major histocompatibility complex (MHC). Animal models confirmed the primary role of MHC in SpA susceptibility and supported the hypothesis that certain enterobacterial infections can trigger SpA. Immunization of mice with proteoglycan aggrecan also can provoke SpA, thus providing the opportunity to study genetic and clinical details of the disease initiation.


Prenatal and postnatal residential usage of insecticides in a multicenter birth cohort in Spain.
This study aimed to describe the residential use of insecticides in a birth cohort in Spain. Study subjects were 2,456 women enrolled into the INMA (Environment and Childhood) birth cohort followed prospectively during pregnancy and in the early postnatal period. The women were recruited at the beginning of their pregnancy between 2003 and 2008 in four regions of Spain. Socio-demographic, environmental and lifestyle information was obtained at two interviews during pregnancy, one at the first (mean:13.8±2.6 weeks of gestation) and the other at the third trimester (mean: 33.3±2.3 weeks of gestation). Information about prenatal use of indoor and outdoor insecticides (type, timing, place of application, place of storage) was obtained from the second interview. In a 3rd interview (mean: 16.2±6.9 months of age of children), information about postnatal indoor and outdoor insecticide use was obtained. Regression models examined the association between demographic and lifestyle factors and pesticide use to determine which characteristics predicted use prenatally and postnatally. Fifty-four percent of women reported using indoor insecticides during pregnancy, 45% in their bedroom and 47% elsewhere in the house. Plug-in devices were the most frequent application methods used in the pregnant woman's bedroom and insecticide sprays elsewhere in the house. The maternal factors related to prenatal use of indoor insecticides were parity, country of birth, educational level, region of residence, having a garden or yard with plants, and living near an agricultural area. These products continued to be used postnatally, although 20% of the women stopped using them. Foetuses and children are especially vulnerable to pesticide exposure; thus knowing how pesticides are used during pregnancy and infancy may be a starting point for the study of their potential effects on health as well as useful for designing preventive actions.


Serum zinc concentrations and depression in persons with Human Immunodeficiency Virus infection: The positive living with HIV (POLH) study.
Low levels of serum zinc concentrations and depression are common in persons infected with Human Immunodeficiency Virus (HIV). Low levels of serum zinc concentrations may increase risk of depression in general population. However, research on the role of zinc in depression among HIV- infected person is limited. We assessed the association between serum zinc concentrations and depression in HIV-infected persons. A cross-sectional survey was conducted among 311 HIV-positive people (177 men and 134 women) aged 18-60 years residing in Kathmandu, Nepal. The atomic absorption method was used to measure serum zinc concentrations and the Beck Depression Inventory (BDI)-Ia method was used to measure depression, with cut off score 20 or higher consistent with clinically significant depression. Relationships were assessed using multiple linear and logistic regression analyses. Serum zinc concentrations were significantly inversely associated with depression in all participants and in men but not in women. Participants with the highest tertile of serum zinc concentrations had a significantly decreased risk of depression in men but not in women. Serum zinc concentrations were inversely associated with depressive symptoms scores in HIV-infected men. Further prospective studies are needed to confirm the role of zinc in depression among persons infected with HIV.


Extracellular Vesicle-Associated TWEAK Contributes to Vascular Inflammation and Remodeling During Acute Cellular Rejection.
Acute cellular rejection (ACR) is a leading cause of graft loss and death after heart transplantation despite effective immunosuppressive therapies. The identification of factors that impair graft vascular barrier function or promote immune cell recruitment during ACR could provide new therapeutic opportunities for the treatment of patients who receive transplants. In 2 ACR cohorts, we found the extracellular vesicle-associated cytokine TWEAK to be elevated during ACR. Vesicular TWEAK promoted expression of proinflammatory genes and the release of chemoattractant cytokines from human cardiac endothelial cells. We conclude that vesicular TWEAK is a novel target with potential therapeutic implications in ACR.


Clinical Outcomes at 1 Year Following Transcatheter Left Atrial Appendage Occlusion in the United States.
The aim of this study was to report 1-year clinical outcomes following commercial transcatheter left atrial appendage occlusion (LAAO) in the United States. The National Cardiovascular Data Registry LAAO Registry was initiated to meet a condition of Medicare coverage and allow the assessment of clinical outcomes. The 1-year rates of thromboembolic events after transcatheter LAAO in such a large cohort of "real-world" patients have not been previously reported. Patients entered into the National Cardiovascular Data Registry LAAO Registry for a Watchman procedure between January 1, 2016, and December 31, 2018, were included. The primary endpoint was ischemic stroke. Key secondary endpoints included the rate of ischemic stroke or systemic embolism, mortality, and major bleeding. Major bleeding was defined as any bleeding requiring hospitalization, and/or causing a decrease in hemoglobin level > 2g/dL, and/or requiring blood transfusion that was not hemorrhagic stroke. The Kaplan-Meier method was used for 1-year estimates of cumulative event rates. The study population consisted of 36,681 patients. The mean age was 76.0 ± 8.1 years, the mean CHA2DS2-VASc score was 4.8 ± 1.5, and the mean HAS-BLED score was 3.0 ± 1.1. Prior stroke was present in 25.5%, clinically relevant bleeding in 69.5%, and intracranial bleeding in 11.9%. Median follow-up was 374 days (IQR: 212-425 days). The Kaplan-Meier-estimated 1-year rate of ischemic stroke was 1.53% (95% CI: 1.39%-1.69%), the rate of ischemic stroke or systemic embolism was 2.19% (95% CI: 2.01%-2.38%), and the rate of mortality was 8.52% (95% CI: 8.19%-8.87%). The 1-year estimated rate of major bleeding was 6.93% (95% CI: 6.65%-7.21%). Most bleeding events occurred between discharge and 45 days following the procedure. This study characterizes important outcomes in a national cohort of patients undergoing transcatheter LAAO in the United States. Clinicians and patients can integrate these data in shared decision making when considering this therapy.


[Bowman-Birk soy inhibitor as an affinity ligand for isolating leukocyte elastase. Inhibition of elastin hydrolysis, catalyzed by leukocyte elastase].
A one-step procedure for human leukocyte elastase purification using an affinity adsorbent based on protein soybean Bowman-Birk proteinase inhibitor has been developed. The leukocyte elastase was purified 70-fold with a 70-100% yield. The enzyme preparations did not contain cathepsin G and displayed a high specific activity. The soybean Bowman-Birk type inhibitor effectively inhibited the elastin hydrolysis by leukocyte elastase both when the enzyme and the inhibitor were simultaneously added to the substrate and after preliminary elastase adsorption on elastin. The inhibitory effect was preserved at high degrees of elastin hydrolysis.


Automated linking of free-text complaints to reason-for-visit categories and International Classification of Diseases diagnoses in emergency department patient record databases.
The use of the International Classification of Diseases system to describe emergency department (ED) case mix has disadvantages. We therefore developed computer algorithms that recognize a combination of words, word fragments, and word patterns to link free-text complaint fields to 20 reason-for-visit categories. We examine the feasibility and reliability of applying these reason-for-visit categories to ED patient-visit databases. We analyzed a database (containing complaints and International Classification of Diseases diagnoses for 1 year's visits to a single ED) using a 3-step process (create initial terms, maximize sensitivity, maximize specificity) to define inclusion and exclusion terms for 20 reason-for-visit categories. To assess the reliability of the reason-for-visit assignment algorithm, we repeated the final 2 steps on a second database, composed of visits sampled from 21 EDs. For each database, we determined the prevalence of complaints that link to each reason-for-visit category and the distributions of International Classification of Diseases, Ninth Revision diagnoses that resulted for all patients and patients stratified by age. The 20 reason-for-visit categories capture 77% of all patients in database 1 (mean age 33.5 years) and 67% of all patients in database 2 (mean age 38.9 years). The percentage of visits captured by the 20 reason-for-visit categories, by age range, for databases 1 and 2 are (respectively) 0 to 2 years (84% and 76%), 3 to 10 years (82% and 74%), 11 to 65 years (76% and 68%), and 66 years or older (69% and 60%). The proportions of all complaints that link to each reason-for-visit category are largely similar between databases. Every complaint field that is linked to each reason-for-visit category includes at least 1 term that relates it to the category title, and the most frequently assigned diagnoses in each reason-for-visit category are those that one would expect to be associated with the reason-for-visit category complaints. The method by which free-text complaint fields are parsed into reason-for-visit categories is feasible and reasonably reliable; the finalized database 1 reason-for-visit category inclusion/exclusion terms lists required only modest changes to work well in database 2. The reason-for-visit categories used here are broadly defined to maximize the proportion of visits that they capture; more narrowly defined reason-for-visit categories will require more extensive revision of their inclusion/exclusion terms lists when used in different databases. A prospective, reason-for-visit-based ED classification system could have several useful applications (including syndromic surveillance), although content validity analysis will be necessary to investigate this hypothesis.


Speeding up temperature-responsive × reversed-phase comprehensive liquid chromatography through the combined exploitation of temperature and flow rate gradients.
Comprehensive two-dimensional liquid chromatography (LC×LC) can provide enhanced resolving power and higher peak capacities for the separation of complex samples. The transfer of fractions of too high eluotropic strength from the first dimension, however, can lead to peak broadening. This process is related to the column dimensions, the flow rates, mobile phase compositions, and stationary phase compatibility. Temperature-responsive LC (TRLC) uses a smart polymer coupled to silica (poly(N-isopropylacrylamide), pNIPAAm), that exhibits a change in polarity upon modest variations in column temperature. Retention is thus modulated by temperature and not by organic solvents, allowing for the use of purely aqueous mobile phases. As these aqueous mobile phases depict a very low eluotropic strength on a reversed-phase column, it facilitates band refocusing at the second-dimension column head in TRLC×RPLC. One of the remaining obstacles of TRLC is the long analysis time. In this research, the potential of this column combination in terms of analyte refocusing will be exploited. First, it is shown that upwards flow gradients can be implemented in the first dimension of TRLC×RPLC. As the flow in the second dimension is maintained at a constant level, a first-dimension flow gradient does not lead to impaired sensitivity and has no negative effects on the resulting peak size. Then, the novel combination of a downwards temperature gradient with an upwards flow gradient will be introduced to speed up the analyses further. Analysis time was, depending on the method used, reduced by 36-54%, as demonstrated by the analysis of mixtures of food additives, phenolic compounds, and small molecule pharmaceuticals mimicking impurity analysis at a 0.05% level.


Anti-oxidant potential of plants and probiotic spp. in alleviating oxidative stress induced by H2O2.
Cells produce reactive oxygen species (ROS) as a metabolic by-product. ROS molecules trigger oxidative stress as a feedback response that significantly initiates biological processes such as autophagy, apoptosis, and necrosis. Furthermore, extensive research has revealed that hydrogen peroxide (H2O2) is an important ROS entity and plays a crucial role in several physiological processes, including cell differentiation, cell signalling, and apoptosis. However, excessive production of H2O2 has been shown to disrupt biomolecules and cell organelles, leading to an inflammatory response and contributing to the development of health complications such as collagen deposition, aging, liver fibrosis, sepsis, ulcerative colitis, etc. Extracts of different plant species, phytochemicals, and Lactobacillus sp (probiotic) have been reported for their anti-oxidant potential. In this view, the researchers have gained significant interest in exploring the potential plants spp., their phytochemicals, and the potential of Lactobacillus sp. strains that exhibit anti-oxidant properties and health benefits. Thus, the current review focuses on comprehending the information related to the formation of H2O2, the factors influencing it, and their pathophysiology imposed on human health. Moreover, this review also discussed the anti-oxidant potential and role of different extract of plants, Lactobacillus sp. and their fermented products in curbing H2O2‑induced oxidative stress in both in-vitro and in-vivo models via boosting the anti-oxidative activity, inhibiting of important enzyme release and downregulation of cytochrome c, cleaved caspases-3, - 8, and - 9 expression. In particular, this knowledge will assist R&D sections in biopharmaceutical and food industries in developing herbal medicine and probiotics-based or derived food products that can effectively alleviate oxidative stress issues induced by H2O2 generation.


Early detection of Alzheimer's disease using neuroimaging.
Neuroimaging is being increasingly used to complement clinical assessments in the early detection of Alzheimer's disease (AD). Structural magnetic resonance imaging (MRI) and metabolic positron emission tomography (FDG-PET) are the most clinically used and promising modalities to detect brain abnormalities in individuals who might be at risk for AD but who have not yet developed symptoms. The knowledge of established risk factors for AD enabled investigators to develop enrichment strategies for longitudinal imaging studies to reduce the sample sizes and study duration. The present review focuses on the results obtained by MRI and FDG-PET studies that examined the preclinical AD stages in several at risk populations: (1) individuals from families with autosomal dominant early-onset AD (FAD), (2) patients with mild cognitive impairment (MCI), particularly in memory, who are at very high risk for declining to AD with an estimated decline rate of 10-30% per year, (3) normal young and middle-age subjects carriers of known susceptibility genes for late-onset AD such as the Apolipoprotein E (ApoE) E4 allele, and (4) as age is the main risk factor for AD, normal elderly individuals followed to the onset of MCI and AD. Overall, these studies show that the use of imaging for the early detection of AD is successful even in the earlier stages of disease when clinical symptoms are not fully expressed and the regional brain damage may be limited.


Effects of beta-chlornaltrexamine on separation distress in chicks.
Intraventricular B-chlornaltrexamine (2 micrograms) increased distress vocalizations (DVs) in chicks, and reduced the ability of intraventricular morphine (.1-.5 micrograms), to inhibit DVs. Object imprinting was not blocked by central CNA, but systemic naloxone (10 mg/kg) did attenuate imprinting to a green but not a red object.


Phage-delivered CRISPR-Cas9 for strain-specific depletion and genomic deletions in the gut microbiome.
Mechanistic insights into the role of the human microbiome in the predisposition to and treatment of disease are limited by the lack of methods to precisely add or remove microbial strains or genes from complex communities. Here, we demonstrate that engineered bacteriophage M13 can be used to deliver DNA to Escherichia coli within the mouse gastrointestinal (GI) tract. Delivery of a programmable exogenous CRISPR-Cas9 system enables the strain-specific depletion of fluorescently marked isogenic strains during competitive colonization and genomic deletions that encompass the target gene in mice colonized with a single strain. Multiple mechanisms allow E. coli to escape targeting, including loss of the CRISPR array or even the entire CRISPR-Cas9 system. These results provide a robust and experimentally tractable platform for microbiome editing, a foundation for the refinement of this approach to increase targeting efficiency, and a proof of concept for the extension to other phage-bacterial pairs of interest.


Texture analysis with a new method in which the region of interest is segmented into multiple layers for radiofrequency amplitude histogram analysis of fibrous rat livers.
The aim of this study was to estimate the severity of fibrosis without a biopsy. The signal-to-noise ratio (SNR), skewness, and kurtosis were measured using a 10-MHz transducer with the texture analysis in conjunction with an alternative method for evaluating fibrous rat livers. This method segments the region of interest (ROI) into multiple layers (sub-ROIs). In each sub-ROI of a homogeneous medium, the histogram of enveloped amplitude of radiofrequency (RF) backscattered echoes resembles a Rayleigh distribution. In theory, SNR, skewness, and kurtosis for Rayleigh statistics are constant and independent of the mean scattering intensity, which is enhanced by such undesirable effects as tissue attenuation, beam diffraction, and incident waveforms. Thus, these values, which are averages of the corresponding sub-ROI values, constitute an unbiased estimator. All fibrous liver specimens were induced using the dimethylnitrosamine method. Fiber content was estimated quantitatively as the fibrosis index by computer processing of pathological images obtained by light microscopy. The SNR, skewness and kurtosis, expressed as averages of corresponding values from each sub-ROI, correlated closely with the fibrosis index. These results make it possible to predict the severity of liver fibrosis from data obtained without resorting to biopsy. The data, obtained from our earlier study on rats, may be used to evaluate human hepatitis quantitatively by measuring these three values. The method may make it possible to estimate the degree of severity of chronic liver disease noninvasively.


Prevalence of hepatitis C virus infection in urban children.
To determine the prevalence of hepatitis C virus (HCV) infection in children with an unknown or negative human immunodeficiency virus (HIV) status attending an urban hospital pediatric primary care clinic, and to identify HCV risk factors in their mothers. This was a cross-sectional study of 1034 children tested for HCV antibodies (anti-HCV) after excluding children known to be HIV-positive. We assessed maternal HCV risk factors through structured interviews with a sample of mothers (n=573) and through review of available medical records (n=347) for a subsample of mother-child pairs. Means, proportions, and 95% confidence intervals were used to estimate the prevalence of anti-HCV and maternal risk factors. One child (0.1%; 95% CI, 0.002, 0.5) was anti-HCV positive. History of blood transfusion was reported by 7% of mothers and intravenous drug use (IVDU) by 1.8%. A subsample of mothers significantly underreported IVDU when compared with medical record review (1.5% vs 7.8%, P<.001). Our findings suggest that universal screening of children for HCV in high-risk urban communities is not warranted. However, self-report may not be reliable for identifying mothers with a history of IVDU, for whom HCV testing is recommended.


Percutaneous drainage of a postoperative intraspinal hematoma using a Tuohy needle.
A 78-year-old man developed a large subdural hematoma extending from T12 to L3 levels following L3 laminectomy and L3-5 posterior spinal fusion. He had associated neurological signs and symptoms. MR imaging showed typical signal characteristics of a subacute intraspinal subdural hematoma. Percutaneous drainage was successfully performed under CT guidance by inserting a Tuohy needle through the L3 laminectomy defect. The catheter packaged with the Tuohy needle was inserted cranially into the hematoma and 30 ml of blood was aspirated. Follow-up MR imaging confirmed resolution of the hematoma and the patient made a rapid recovery.


Computational modeling for prediction of the shear stress of three-dimensional isotropic and aligned fiber networks.
Interstitial flow (IF) is a creeping flow through the interstitial space of the extracellular matrix (ECM). IF plays a key role in diverse biological functions, such as tissue homeostasis, cell function and behavior. Currently, most studies that have characterized IF have focused on the permeability of ECM or shear stress distribution on the cells, but less is known about the prediction of shear stress on the individual fibers or fiber networks despite its significance in the alignment of matrix fibers and cells observed in fibrotic or wound tissues. In this study, I developed a computational model to predict shear stress for different structured fibrous networks. To generate isotropic models, a random growth algorithm and a second-order orientation tensor were employed. Then, a three-dimensional (3D) solid model was created using computer-aided design (CAD) software for the aligned models (i.e., parallel, perpendicular and cubic models). Subsequently, a tetrahedral unstructured mesh was generated and flow solutions were calculated by solving equations for mass and momentum conservation for all models. Through the flow solutions, I estimated permeability using Darcy's law. Average shear stress (ASS) on the fibers was calculated by averaging the wall shear stress of the fibers. By using nonlinear surface fitting of permeability, viscosity, velocity, porosity and ASS, I devised new computational models. Overall, the developed models showed that higher porosity induced higher permeability, as previous empirical and theoretical models have shown. For comparison of the permeability, the present computational models were matched well with previous models, which justify our computational approach. ASS tended to increase linearly with respect to inlet velocity and dynamic viscosity, whereas permeability was almost the same. Finally, the developed model nicely predicted the ASS values that had been directly estimated from computational fluid dynamics (CFD). The present computational models will provide new tools for predicting accurate functional properties and designing fibrous porous materials, thereby significantly advancing tissue engineering.


Description of a new species of Odontochrydium Brauns (Hymenoptera: Chrysididae) from the Arabian Peninsula.
Odontochrydium arabicum sp. nov., a new chrysidid species from Oman, southwestern Saudi Arabia, and Yemen is described, illustrated and compared with the African species, O. bicristatum Rosa from Kenya.


Supplemental Scleral Buckle for the Management of Rhegmatogenous Retinal Detachment by Pars Plana Vitrectomy: A Meta-Analysis of Randomized Controlled Trials.
The present review aimed to synthesize evidence from randomized controlled trials (RCTs) that compared outcomes of pars plana vitrectomy (PPV) with and without a supplementary scleral buckle (SB) for management of rhegmatogenous retinal detachment (RRD). The authors searched MEDLINE, Embase, and CENTRAL to identify RCTs in English that compared PPV with and without supplemental SB. Risk of bias was assessed according to the Cochrane Risk of Bias 2 tool. We present risk ratios (RRs), mean differences (MDs), and 95% confidence intervals (CIs) estimated using random-effects meta-analyses. We identified 6 RCTs involving 705 eyes. Primary reattachment (6 studies, 345 eyes PPV, 324 eyes PPV + SB; RR 0.99, 95% CI 0.93-1.06, I2 = 0%, p = 0.78) and final anatomic success rates (4 studies, 272 eyes PPV, 267 eyes PPV + SB; RR 1.00, 95% CI 0.98-1.02, I2 = 0%, p = 0.89) were similar between the 2 groups. Postoperative visual acuity improvement (5 studies, 244 eyes PPV, 222 eyes PPV + SB; MD 6.09 letters, 95% CI -0.47-12.64, I2 = 69%, p = 0.07) and frequency of adverse events (6 studies, 1,294 observations PPV, 1,221 observations PPV + SB; RR 0.76, 95% CI 0.57-1.01, I2 = 25%, p = 0.06) likewise did not differ significantly between the treatment groups. Low-certainty evidence from RCTs did not demonstrate a benefit in placement of a supplemental SB during vitrectomy for management of RRD in the current analysis. Additional high-quality trials are needed to provide more precise estimates of the effect.


High-performance compliant thermoelectric generators with magnetically self-assembled soft heat conductors for self-powered wearable electronics.
Softening of thermoelectric generators facilitates conformal contact with arbitrary-shaped heat sources, which offers an opportunity to realize self-powered wearable applications. However, existing wearable thermoelectric devices inevitably exhibit reduced thermoelectric conversion efficiency due to the parasitic heat loss in high-thermal-impedance polymer substrates and poor thermal contact arising from rigid interconnects. Here, we propose compliant thermoelectric generators with intrinsically stretchable interconnects and soft heat conductors that achieve high thermoelectric performance and unprecedented conformability simultaneously. The silver-nanowire-based soft electrodes interconnect bismuth-telluride-based thermoelectric legs, effectively absorbing strain energy, which allows our thermoelectric generators to conform perfectly to curved surfaces. Metal particles magnetically self-assembled in elastomeric substrates form soft heat conductors that significantly enhance the heat transfer to the thermoelectric legs, thereby maximizing energy conversion efficiency on three-dimensional heat sources. Moreover, automated additive manufacturing paves the way for realizing self-powered wearable applications comprising hundreds of thermoelectric legs with high customizability under ambient conditions.


Socioeconomic differences in weight retention, weight-related attitudes and practices in postpartum women.
To determine if there is a socioeconomic status (SES) gradient in postpartum weight retention in women living in the UK, and examine SES differences in weight-related attitudes and practices in the postpartum period. Women (n = 2745) who had full-term live births between July and December 1999 in four London hospitals were eligible to participate in this self-report postal questionnaire study. The questionnaire included items on socio-demographic characteristics, pre-pregnancy weight, postpartum height and weight, pregnancy weight gain and duration, and postpartum weight-related attitudes (body image and weight beliefs) and practices (weight control and weight monitoring). Education was used as the indicator of SES. Questionnaires were returned by 954 women (35%) on average eight months postpartum. Median postpartum weight retention was 2.7 kg and was significantly higher in the medium and lower SES women (3.2 kg) than higher SES women (1.8 kg) despite no difference in pregnancy weight gain. A greater proportion of higher SES women believed they would return to their pre-pregnant weight, and they engaged in more frequent weight monitoring. There were no SES differences in body dissatisfaction or the proportion of women trying to lose weight postpartum. In the postpartum period, women of higher SES retained less weight than women of lower SES. There were also differences in weight-related attitudes and frequency of weight monitoring across SES groups.


Low-dose SN-38 with paclitaxel induces lethality in human uterine cervical adenocarcinoma cells by increasing caspase activity.
Combination of anticancer drugs may provide a rational molecular basis for novel chemotherapeutic strategies. Paclitaxel and SN-38 (an active metabolite of CPT-11) are effective for many kinds of cancer. Therefore, we investigated the possibility that combination of these drugs could be effective against cervical adenocarcinoma cells. In this study, we examined cell growth inhibition after 96 h using the MTT assay and examined the release of fragmented DNA into the cytoplasm during apoptotic cell death by PI staining. Single and combined use of paclitaxel and SN-38 produced significant cytolethality against the cervical adenocarcinoma cell line CAC-1. Addition of a low concentration of SN-38 reduced the IC50 value of paclitaxel compared to that without SN-38, although the low concentration of paclitaxel did not enhance the cytotoxicity of SN-38. FACS scan analysis suggested that these drugs induced apoptosis and cell cycle arrest, and that caspase-3 and -7 were activated in the process. MTT assay and the IC50 demonstrated that paclitaxel had strong cytotoxicity against CAC-1 as well as other cancer cells. In this study, though only a single cell line was used for the experiment and the data are limited, our results suggest that paclitaxel together with low-dose CPT-11 is a promising basis for a new combination cancer chemotherapy.


An Optimal Frequency in Ca2+ Oscillations for Stomatal Closure Is an Emergent Property of Ion Transport in Guard Cells.
Oscillations in cytosolic-free Ca(2+) concentration ([Ca(2+)]i) have been proposed to encode information that controls stomatal closure. [Ca(2+)]i oscillations with a period near 10 min were previously shown to be optimal for stomatal closure in Arabidopsis (Arabidopsis thaliana), but the studies offered no insight into their origins or mechanisms of encoding to validate a role in signaling. We have used a proven systems modeling platform to investigate these [Ca(2+)]i oscillations and analyze their origins in guard cell homeostasis and membrane transport. The model faithfully reproduced differences in stomatal closure as a function of oscillation frequency with an optimum period near 10 min under standard conditions. Analysis showed that this optimum was one of a range of frequencies that accelerated closure, each arising from a balance of transport and the prevailing ion gradients across the plasma membrane and tonoplast. These interactions emerge from the experimentally derived kinetics encoded in the model for each of the relevant transporters, without the need of any additional signaling component. The resulting frequencies are of sufficient duration to permit substantial changes in [Ca(2+)]i and, with the accompanying oscillations in voltage, drive the K(+) and anion efflux for stomatal closure. Thus, the frequency optima arise from emergent interactions of transport across the membrane system of the guard cell. Rather than encoding information for ion flux, these oscillations are a by-product of the transport activities that determine stomatal aperture.


BMDExpress: a software tool for the benchmark dose analyses of genomic data.
Dose-dependent processes are common within biological systems and include phenotypic changes following exposures to both endogenous and xenobiotic molecules. The use of microarray technology to explore the molecular signals that underlie these dose-dependent processes has become increasingly common; however, the number of software tools for quantitatively analyzing and interpreting dose-response microarray data has been limited. We have developed BMDExpress, a Java application that combines traditional benchmark dose methods with gene ontology classification in the analysis of dose-response data from microarray experiments. The software application is designed to perform a stepwise analysis beginning with a one-way analysis of variance to identify the subset of genes that demonstrate significant dose-response behavior. The second step of the analysis involves fitting the gene expression data to a selection of standard statistical models (linear, 2 degrees polynomial, 3 degrees polynomial, and power models) and selecting the model that best describes the data with the least amount of complexity. The model is then used to estimate the benchmark dose at which the expression of the gene significantly deviates from that observed in control animals. Finally, the software application summarizes the statistical modeling results by matching each gene to its corresponding gene ontology categories and calculating summary values that characterize the dose-dependent behavior for each biological process and molecular function. As a result, the summary values represent the dose levels at which genes in the corresponding cellular process show transcriptional changes. The application of microarray technology together with the BMDExpress software tool represents a useful combination in characterizing dose-dependent transcriptional changes in biological systems. The software allows users to efficiently analyze large dose-response microarray studies and identify reference doses at which particular cellular processes are altered. The software is freely available at http://sourceforge.net/projects/bmdexpress/ and is distributed under the MIT Public License.


Glutamatergic input-output properties of thalamic astrocytes.
Astrocytes in the somatosensory ventrobasal (VB) thalamus of rats respond to glutamatergic synaptic input with metabotropic glutamate receptor (mGluR) mediated intracellular calcium ([Ca²⁺](i)) elevations. Astrocytes in the VB thalamus also release the gliotransmitter (GT) glutamate in a Ca²⁺-dependent manner. The tripartite synapse hypothesis posits that astrocytic [Ca²⁺](i) elevations resulting from synaptic input releases gliotransmitters that then feedback to modify the synapse. Understanding the dynamics of this process and the conditions under which it occurs are therefore important steps in elucidating the potential roles and impact of GT release in particular brain activities. In this study, we investigated the relationship between VB thalamus afferent synaptic input and astrocytic glutamate release by recording N-methyl-D-aspartate (NMDA) receptor-mediated slow inward currents (SICs) elicited in neighboring neurons. We found that Lemniscal or cortical afferent stimulation, which can elicit astrocytic [Ca²⁺](i) elevations, do not typically result in the generation of SICs in thalamocortical (TC) neurons. Rather, we find that the spontaneous emergence of SICs is largely resistant to acute afferent input. The frequency of SICs, however, is correlated to long-lasting afferent activity. In contrast to short-term stimulus-evoked GT release effects reported in other brain areas, astrocytes in the VB thalamus do not express a straightforward input-output relationship for SIC generation but exhibit integrative characteristics.


Cardiorespiratory fitness as a quantitative predictor of the risk of stroke: a dose-response meta-analysis.
Cardiorespiratory fitness (CRF) is closely related to our health, but whether high cardiorespiratory fitness could reduce stroke risk remains controversial. We used a meta-analysis to examine the overall association between cardiorespiratory fitness and stroke incidence. A systematic search was performed in PubMed, EMBASE, and Web of science. We estimated the overall relative risk (RR) of stroke incidence for high levels of CRF individuals versus individuals with low levels of CRF. Meanwhile, we made a quantitative analysis of the association between CRF and the risk of stroke. 14 cohort studies containing 1,409,340 participants were included in this meta-analysis, and 23,894 stroke patients were observed. The meta-analysis documented that the high-CRF individuals had a 42% lower risk of stroke (RR_0.58; 95% CI 0.51-0.66) compared with low-CRF individuals. Besides, subgroup analysis showed that the inverse association of CRF with the risk of stroke was consistent. There are 29% lower risk of ischemic stroke (RR_0.71; 95% CI 0.54-0.93) and 31% lower risk of hemorrhagic stroke (RR_0.69; 95% CI 0.47-1.00). Dose-response analysis showed that every "unit-dose" increment of five metabolic equivalents (METs) reduced a 15% lower risk of stroke (RR_0.85; 95% CI 0.79-0.91). This meta-analysis provides the evidence that better CRF was with a lower risk of stroke incidence.


A comparative study: perfusion of the micro- and macrocirculation as a function of the hematocrit value.
The fluidity (the inverse of viscosity) of red blood cell (RBC) suspensions in vivo was estimated by means of microcirculatory measurements such as RBC flow velocity, micropressure in arterioles and venules, and vessel geometry, and by means of simultaneous macrocirculatory measurements such as volume flow and perfusion pressure in the whole organ. These in vivo data were compared to in vitro data obtained by viscometry. The experiments were performed on the isolated rat mesentery perfused with a nonaggregating and an aggregating suspension: Human RBC were either suspended in Ringer's or Ficoll 400 solution. The tissue was perfused at various perfusion pressures and hematocrit values. The microcirculatory perfusion was recorded by means of microscopy using a video TV system. Five major results have been identified: First, microfluidities calculated from velocity data in capillaries of the mesenteric membrane were almost identical to the fluidities calculated from macroflow data (volume flow rates and perfusion pressure in the whole organ). Second, in vivo fluidities of both suspensions decrease with increasing hematocrit value but seem to be independent of driving pressure between 4 and 10 kPa. Third, the fluidity of the Ficoll suspensions is lower than the fluidity of the Ringer's suspensions by the same ratio as the continuous phases. Fourth, the in vivo fluidities of the Ringer's suspensions and the Ficoll suspensions for hematocrit values from 20 to 70% and a range of wall shear stresses from 0.6 to 1 Pa were higher than those measured in vitro. Finally, it has been quantified that an increasing number of vessels became stagnant (that is packed by red blood cells) at high hematocrit values, low perfusion pressure, and increased aggregability of RBC.


On the dispersal of leatherback turtle hatchlings from Mesoamerican nesting beaches.
So little is known about the early life history of leatherback turtles (Dermochelys coriacea) from hatchling to adulthood that this period has been termed the 'lost years'. For critically endangered eastern Pacific leatherback populations, continued and rapid declines underscore the urgent need to develop conservation strategies across all life stages. We investigate leatherback hatchling dispersal from four Mesoamerican nesting beaches using passive tracer experiments within a regional ocean modelling system. The evolution of tracer distribution from each of the nesting beaches showed the strong influence of eddy transport and coastal currents. Modelled hatchlings from Playa Grande, Costa Rica, were most likely to be entrained and transported offshore by large-scale eddies coincident with the peak leatherback nesting and hatchling emergence period. These eddies potentially serve as 'hatchling highways', providing a means of rapid offshore transport away from predation and a productive refuge within which newly hatched turtles can develop. We hypothesize that the most important leatherback nesting beach remaining in the eastern Pacific (Playa Grande) has been evolutionarily selected as an optimal nesting site owing to favourable ocean currents that enhance hatchling survival.


Splenic function in sickle cell disease in the Eastern Province of Saudi Arabia.
The sickle cell disease that occurs in the Eastern Province of Saudi Arabia is reported to be clinically benign. It is biochemically characterized by high levels of fetal hemoglobin. Twenty-four Saudi patients with sickle cell disease were compared with 22 American patients. As a group, the Saudi patients were less anemic and had less hemolysis, microcytic RBC, and much higher levels of Hb F. Splenic function was assessed by enumeration of pocked RBC. Seventeen Saudi patients had low numbers of Pk RBC, indicating normal or nearly normal splenic function, whereas all American patients had markedly decreased splenic function and high numbers of Pk RBC. Low levels of Pk RBC were strongly associated with high levels of Hb F. The genetic basis of the milder sickle cell disease in Saudi Arabia has not been elucidated, but may involve multiple genetic factors. Although the sickle cell disease in Arab patients of eastern Saudi Arabia is often less severe than that in America, it is far from "benign," and some patients have severe clinical courses similar to those in patients in the West.


Signal transducing membrane complexes of photoreceptor outer segments.
Signal transduction in outer segments of vertebrate photoreceptors is mediated by a series of reactions among multiple polypeptides that form protein-protein complexes within or on the surface of the disk and plasma membranes. The individual components in the activation reactions include the photon receptor rhodopsin and the products of its absorption of light, the three subunits of the G protein, transducin, the four subunits of the cGMP phosphodiesterase, PDE6 and the four subunits of the cGMP-gated cation channel. Recovery involves membrane complexes with additional polypeptides including the Na(+)/Ca(2+), K(+) exchanger, NCKX2, rhodopsin kinases RK1 and RK7, arrestin, guanylate cyclases, guanylate cyclase activating proteins, GCAP1 and GCAP2, and the GTPase accelerating complex of RGS9-1, G(beta5L), and membrane anchor R9AP. Modes of membrane binding by these polypeptides include transmembrane helices, fatty acyl or isoprenyl modifications, polar interactions with lipid head groups, non-polar interactions of hydrophobic side chains with lipid hydrocarbon phase, and both polar and non-polar protein-protein interactions. In the course of signal transduction, complexes among these polypeptides form and dissociate, and undergo structural rearrangements that are coupled to their interactions with and catalysis of reactions by small molecules and ions, including guanine nucleotides, ATP, Ca(2+), Mg(2+), and lipids. The substantial progress that has been made in understanding the composition and function of these complexes is reviewed, along with the more preliminary state of our understanding of the structures of these complexes and the challenges and opportunities that present themselves for deepening our understanding of these complexes, and how they work together to convert a light signal into an electrical signal.


Modification by transferrin increases the efficiency of delivery and the photodynamic effect of the quantum dot-phthalocyanine complex on A431 cells.
Hybrid complexes of fluorescent nanoparticles and tetrapyrrole dyes are currently considered as promising third-generation photosensitizers for photodynamic therapy, including cancer treatment. Using nanoparticles as a platform for delivery of photosensitizers to target cells can increase the efficiency of photodynamic action. In this work, we synthesized a complex of polymer-coated CdSe/ZnS quantum dots, substituted phthalocyanines and human transferrin. Such complexes effectively enter human epidermoid carcinoma cells (A431) due to transferrin-mediated endocytosis and are localized in the perinuclear compartment. We observed an efficient excitation energy transfer from the quantum dot to phthalocyanine in the cells, which indicates stability of the complex upon its internalization. It was shown that the photodynamic activity of hybrid complexes covalently bonded to transferrin is 15% higher than the activity of unmodified hybrid complexes. Our results confirm the feasibility of using fluorescent nanoparticles to enhance the photodynamic properties of photosensitizers based on tetrapyrrole dyes.


Bioorthogonal Caging-Group-Free Photoactivatable Probes for Minimal-Linkage-Error Nanoscopy.
Here we describe highly compact, click compatible, and photoactivatable dyes for super-resolution fluorescence microscopy (nanoscopy). By combining the photoactivatable xanthone (PaX) core with a tetrazine group, we achieve minimally sized and highly sensitive molecular dyads for the selective labeling of unnatural amino acids introduced by genetic code expansion. We exploit the excited state quenching properties of the tetrazine group to attenuate the photoactivation rates of the PaX, and further reduce the overall fluorescence emission of the photogenerated fluorophore, providing two mechanisms of selectivity to reduce the off-target signal. Coupled with MINFLUX nanoscopy, we employ our dyads in the minimal-linkage-error imaging of vimentin filaments, demonstrating molecular-scale precision in fluorophore positioning.


Rationale for the use of radiolabelled peptides in diagnosis and therapy.
Nuclear medicine techniques are becoming more important in imaging oncological and infectious diseases. For metabolic imaging of these diseases, antibody and peptide imaging are currently used. In recent years peptide imaging has become important, therefore the rationale for the use of peptide imaging is described in this article. Criteria for a successful peptide tracer are a high target specificity, a high binding affinity, a long metabolic stability and a high target-to-background ratio. Tracer internalization is also beneficial. For oncological imaging, many tracers are available, most originating from regulatory peptides, but penetrating peptides are also being developed. Peptides for imaging inflammatory and infectious diseases include regulatory peptides, antimicrobial peptides and others. In conclusion, for the imaging of oncological, imflammatory and infectious diseases, many promising peptides are being developed. The ideal peptide probe is characterized by rapid and specific target localization and binding with a high tumour-to-background ratio.


The role of arginine vasopressin in human labour: functional studies, fetal production and localisation of V1a receptor mRNA.
To investigate labour-associated changes in: 1. the myometrial contractile response to arginine vasopressin compared with oxytocin in vitro 2. fetal production of arginine vasopressin and 3. myometrial vasopressin V1a receptor mRNA. The contractile response to vasopressin (compared with oxytocin) was investigated in paired myometrial strips in vitro. Blood was taken from the umbilical artery and vein at delivery and arginine vasopressin measured by radio-immunoassay. V1a receptor mRNA was determined by in situ hybridisation. Myometrium was more sensitive to arginine vasopressin than oxytocin (P<0.05 for frequency, amplitude and activity integral in paired strips) after, but not before labour. There was a marked umbilical arteriovenous difference in arginine vasopressin concentration at delivery suggesting fetal production which was not influenced by labour. Myometrial vasopressin V1a receptor mRNA was not increased after the onset of labour. The human uterus is extremely sensitive to arginine vasopressin in vitro. Arginine vasopressin is produced by the fetus but fetal formation is not increased during labour.


Hand, foot, and mouth disease in China: patterns of spread and transmissibility.
There were large outbreaks of hand, foot, and mouth disease in both 2008 and 2009 in China. Using the national surveillance data since 2 May 2008, we summarized the epidemiologic characteristics of the recent outbreaks. Using a susceptible-infectious-recovered transmission model, we evaluated the transmissibility of the disease and potential risk factors. Children ages 1.0 to 2.9 years were the most susceptible to hand, foot, and mouth disease (odds ratios [OR] >2.3 as compared with other age-groups). Infant cases had the highest incidences of severe disease (ORs >1.4) and death (ORs >2.4), as well as the longest delay from symptom onset to diagnosis (2.3 days). Boys were more susceptible than girls (OR = 1.56 [95% confidence interval = 1.56-1.57]). A 1-day delay in diagnosis was associated with increases in the odds of severe disease by 40% (39%-42%) and in the odds of death by 54% (44%-65%). Compared with Coxsackie A16, enterovirus 71 is more strongly associated with severe disease (OR = 16 [13-18]) and death (OR = 40 [13-127]). The estimated local effective reproductive numbers among prefectures ranged from 1.4 to 1.6 (median = 1.4) in spring and stayed below 1.2 in other seasons. A higher risk of transmission was associated with temperatures in the range of 70° F to 80°F, higher relative humidity, higher [corrected] wind speed, more precipitation, greater population density, and [corrected] periods during which schools were open. Hand, foot, and mouth disease is a moderately transmittable infectious disease, mainly among preschool children. Enterovirus 71 was responsible for most severe cases and fatalities. Mixing of asymptomatically infected children in schools might have contributed to spread the of infection. Timely diagnosis may be [corrected] key to reducing the high mortality rate in infants.


Potent and selective bicyclic lactam inhibitors of thrombin: Part 2: P1 modifications.
The synthesis and antithrombotic activity of a series of nonpeptide bicyclic thrombin inhibitors is described. We have explored the SAR with modifications to the P1 site. The introduction of arginine mimetics at the P1 site led to potent and selective thrombin inhibitors.


Bronchioloalveolar cell carcinoma of the lung: a clinicopathological study.
Thirty-nine patients with bronchioloalveolar carcinoma were reviewed. The primary lung tumor from 27 patients was examined and divided by histological criteria into three categories. The type 1 pattern was associated with a mean survival of 4.7 years. A mean survival of 3.8 years was attained in patients with type 2. Patients with the type 3 pattern had an average survival of 1.4 years. There was a statistically significant difference in survival when types 1 and 2 together were compared with type 3 (rho less than 0.05). Another statistically significant finding was a mean survival of 5.2 years in patients with negative lymph nodes after surgical resection and a 2.2 year mean survival in patients with positive nodes. The tumor histology of bronchioloalveolar carcinoma should be examined carefully to obtain helpful information in predicting survival. We recommend that these tumors be classified as well-differentiated or poorly differentiated bronchioloalveolar carcinoma.


[Advances in transoral robotic surgery].
The role of transoral robotic surgery (TORS) in the treatment of head and neck tumors has expanded in the last decade. We present the development and current advances in TORS along with the current indications and contraindications, and describe future developments. We present our own studies and review those in the literature. Since approval of the da Vinci® system, the number of TORS cases has increased significantly. The main indications are tumors of the oropharynx and supraglottis. Most published studies are retrospective case series with no control group. In addition to the further development of the da Vinci® system, the introduction of the Flex®-system is a significant progression. The costs of using robotic systems are high. Technical improvement of robotic systems and the development of new surgical techniques will further expand the indications for TORS. The value of TORS needs to be assessed in prospective controlled studies.


Objectively measured active travel and uses of activity-friendly neighborhood resources: Does change in use relate to change in physical activity and BMI?
Few studies examine how objectively measured use of local physical activity resources contributes to objectively-measured healthy physical activity and weight changes over time. We utilized objective measures to test whether changes in active travel and uses of three physical activity (PA) resources-parks, recreation centers, and transit- related to changes in PA and BMI. Adults (n = 536) in Salt Lake City, UT, wore accelerometer and GPS units in 2012 and 2013, before and after neighborhood rail completion. Regression outcomes included accelerometer counts per minute (cpm), MVPA (moderate-to-vigorous activity minutes/10 h accelerometer wear) and measured BMI; key predictors were changes in active travel and PA resource uses (former and new uses). Significant results (all p < 0.05) showed that increased active travel related to increased total PA (59.86 cpm and 8.50 MVPA); decreased active travel related to decreased MVPA (- 3.01 MVPA). Poorer outcomes were seen after discontinuing use of parks (- 36.29 cpm, - 5.73 MVPA, and + 0.44 BMI points), recreation centers (- 6.18 MVPA), and transit (- 48.14 cpm, - 5.43 MVPA, and + 0.66 BMI). Healthier outcomes were seen after commencing use of parks (29.83 cpm, 5.25 MVPA), recreation centers (44.63 cpm) and transit (38.44 cpm, 4.17 MVPA, and - 0.56 BMI). Transit and park/recreational center uses were unrelated, although park users were more likely to be recreation center users. Active travel and use of three neighborhood PA resources relate to healthy activity and could be fostered by policy and design.


A study investigating the level of satisfaction with the health services provided by the Pharmacist at ENT hospital, Eastern Region Alahsah, Kingdom of Saudi Arabia.
The current study aims to evaluate the patient's level of satisfaction with health care services provided by the pharmacist at Aljaber ENT hospital, Eastern Region Alahsah, Kingdom of Saudi Arabia. A cross sectional study was planned from 1st March 2011 until 31st May 2011. A 27 item questionnaire was used, scoring of the responses was done to classify the patient satisfaction into sublevels. The maximum possible score was 36; those scoring less than twenty were graded as poor satisfaction level followed by moderate satisfaction level 21-25, good satisfaction level 26-30 and high satisfaction level 31-36. Statistical package for social science version 13® was used to analyze data, One-way ANOVA and independent sample t-test were applied to see the differences in the level of satisfaction. Every third patient visiting pharmacy was given a chance to participate in this study. A total of N = 991 patients were randomized using the pharmacy appointment number. Of whom 657 patients have shown willingness to participate in this study. The response rate of this study was 66.30%, most of the respondents 383 (58.1%) were male ranging from the age group of 21-40 years with a mean age of 32 years SD 9.73. The mean score for all patients was 26.15 SD ±3.4. Among all the demographic variables a significant difference in satisfaction level was found among in terms of age (df = 8, F = 8.36, p = <0.001(∗)), gender (t = -4.089, df = 656, p=<0.001(∗)) and race (df = 2, F = 8.47, p = <0.001. The satisfaction level among Saudi nationals was least in comparison to Egyptians and others. In general, it is seen that respondents of age 56-60 years were most satisfied with the healthcare services provided by the pharmacist. In addition, the satisfaction level was higher among female patients in comparison to men.


Combination of the human prolyl isomerase FKBP12 with unrelated chaperone domains leads to chimeric folding enzymes with high activity.
Folding enzymes often use distinct domains for the binding of substrate proteins ("chaperone domains") and for the catalysis of slow folding reactions such as disulfide formation or prolyl isomerization. The human prolyl isomerase FKBP12 is a small single-domain protein without a chaperone domain. Its very low folding activity could previously be increased by inserting the chaperone domain from the homolog SlyD (sensitive-to-lysis protein D) of Escherichia coli. We now inserted three unrelated chaperone domains into human FKBP12: the apical domain of the chaperonin GroEL from E. coli, the chaperone domain of protein disulfide isomerase from yeast, or the chaperone domain of SurA from the periplasm of E. coli. All three conveyed FKBP12 with a high affinity for unfolded proteins and increased its folding activity. Substrate binding and release of the chimeric folding enzymes were found to be very fast. This allows rapid substrate transfer from the chaperone domain to the catalytic domain and ensures efficient rebinding of protein chains that were unable to complete folding. The advantage of having separate sites, first for generic protein binding and then for specific catalysis, explains why our construction of the artificial folding enzymes with foreign chaperone domains was successful.


Tumor microenvironment for cancer stem cells.
Tumor tissues consist of heterogeneous cancer cells including cancer stem cells (CSCs) that can terminally differentiate into cancer cells. Tissue-specific stem cells in normal organs maintain their stemness in a specific microenvironment, the stem cell niche; several studies have suggested that there are specific microenvironments that maintain CSCs in an immature phenotype. Cell types in a CSC niche vary from fibroblasts, to endothelial cells, immune cells, and so on; these non-cancer cells have been suggested to change their original features in the normal tissue/organ and to acquire a phenotype that protects CSCs from anticancer therapies. Therefore, to kill CSCs, we need to understand the cellular and molecular mechanisms involved in the maintenance of the immature phenotype of CSCs and in drug resistance.


The effects of movement, relaxation, and education on the stress levels of women with subclinical levels of bulimia.
The purpose of this study was to assess the impact of a multidisciplinary intervention program on the attitudes and symptoms associated with bulimia nervosa (BN). The Bulimia Test (BULIT) and subscales from the Eating Disorder Inventory-2 (EDI-2) associated with BN were administered to 373 females to determine eligibility for participation in the study. In order to qualify for the study, participants had to be female, not be anorexic, and meet one of four criteria indicating that they had some of the symptoms of BN. Following the screening, 12 females were randomly assigned to a control group (C, n=6) or an intervention group (I, n=6). The I group then participated in an 8-week multidisciplinary intervention program consisting of small group discussions, movement improvisation, and relaxation techniques. Dependent variables consisted of scores from standardized instruments for anxiety, self-esteem, and BN. A multivariate analysis of variance (MANOVA) on the difference score from post- to pretest was calculated for state and trait anxiety. That analysis indicated that compared to the C group, which showed no reduction in anxiety, the I group had a significant reduction in anxiety following the intervention program. No significant differences were found between groups for self-esteem or symptoms of BN. Conclusions were that anxiety levels were lowered in the I group; however, attitudes or behaviors associated with BN were not affected by the intervention.


Diagnostic utility of QuantiFERON-TB Gold In-Tube test in pediatric tuberculosis disease in Taiwanese children.
To compare the performance of a commercial interferon-gamma release assay, QuantiFERON TB Gold-in-Tube (QFG-IT) with the tuberculin skin test (TST) in Taiwanese children for the diagnosis of active tuberculosis (TB). A retrospective chart analysis of pediatric patients (<18 years of age) who underwent QFG-IT tests and TST for the confirmation of active TB between January 2008 and June 2014. The sensitivity of QFG-IT was 100% [95% confidence interval (CI): 63.1-100], versus sensitivity of 62.5% for TST (95% CI 24.5-91.5). The positive predictive value of QFG-IT was 100 (95% CI: 89.7-100), while the negative predictive value for TST was 86.9% (95% CI: 67-96.3). Among three patients with Bacillus Calmette-Guérin (BCG) osteitis, two patients with TST were positive, but all tested samples for QFG-IT were negative. QFG-IT assay was more sensitive for the diagnosis of TB disease than TST in an intermediate burden population with universal neonatal BCG vaccination. The increased recognition of BCG induced osteitis in recent years has alerted physicians that BCG induced lesions should be suspected when TST is positive but QFG-IT is negative. Despite higher costs for QFG-IT than TST, they have additional value for the diagnosis of active TB and should be performed when a diagnosis of TB remains in doubt.


Wide prevalence of hybridization in two sympatric grasshopper species may be shaped by their relative abundances.
Hybridization between species is of conservation concern as it might threaten the genetic integrity of species. Anthropogenic factors can alter hybridization dynamics by introducing new potentially hybridizing species or by diminishing barriers to hybridization. This may even affect sympatric species pairs through environmental change, which so far has received little attention. We studied hybridization prevalence and the underlying behavioral mechanisms in two sympatric grasshopper species, a rare specialist (Chorthippus montanus) and a common generalist (Chorthippus parallelus). We conducted a mate choice experiment with constant intraspecific density and varying heterospecific density, i.e. varying relative frequency of both species. Mate choice was frequency-dependent in both species with a higher risk of cross-mating with increasing heterospecific frequency, while conspecific mating increased linearly with increasing conspecific density. This illustrates that reproductive barriers could be altered by environmental change, if the relative frequency of species pairs is affected. Moreover, we performed a microsatellite analysis to detect hybridization in twelve syntopic populations (and four allotopic populations). Hybrids were detected in nearly all syntopic populations with hybridization rates reaching up to 8.9 %. Genetic diversity increased for both species when hybrids were included in the data set, but only in the common species a positive correlation between hybridization rate and genetic diversity was detected. Our study illustrates that the relative frequency of the two species strongly determines the effectiveness of reproductive barriers and that even the more choosy species (Ch. montanus) may face a higher risk of hybridization if population size decreases and its relative frequency becomes low compared to its sister species. The asymmetric mate preferences of both species may lead to quasi-unidirectional gene flow caused by unidirectional backcrossing. This might explain why genetic diversity increased only in the common species, but not in the rare one. Altogether, the hybridization rate was much higher than expected for a widely sympatric species pair.


Effect of inoculation on strawberry fermentation and acetification processes using native strains of yeast and acetic acid bacteria.
The aim of this work was to analyze the microbiota involved in the traditional vinegar elaboration of strawberry fruit during a spontaneous and inoculated process. In the spontaneous processes, low biodiversity was detected in both alcoholic fermentation (AF) and acetification. Nevertheless, a strain of Saccharomyces cerevisiae and of Acetobacter malorum were selected and tested as starter cultures in the inoculation study. The inoculated processes with these strains were compared with another spontaneous process, yielding a significant reduction in time for AF with a total imposition of the S. cerevisiae strain. The resulting strawberry wine was acetified in different containers (glass and wood) yielding an initial imposition of the A. malorum inoculated strain, although displacement by Gluconacetobacter species was observed in the wood barrels.


RNA-dependent recruitment of the origin recognition complex.
The origin recognition complex (ORC) has an important function in determining the initiation sites of DNA replication. In higher eukaryotes, ORC lacks sequence-specific DNA binding, and the mechanisms of ORC recruitment and origin determination are poorly understood. ORC is recruited with high efficiency to the Epstein-Barr virus origin of plasmid replication (OriP) through a complex mechanism involving interactions with the virus-encoded EBNA1 protein. We present evidence that ORC recruitment to OriP and DNA replication function depends on RGG-like motifs, referred to as LR1 and LR2, in the EBNA1 amino-terminal domain. Moreover, we show that LR1 and LR2 recruitment of ORC is RNA dependent. HMGA1a, which can functionally substitute for LR1 and LR2 domain, can also recruit ORC in an RNA-dependent manner. EBNA1 and HMGA1a RGG motifs bound to structured G-rich RNA, as did ORC1 peptides, which interact with EBNA1. RNase A treatment of cellular chromatin released a fraction of the total ORC, suggesting that ORC association with chromatin, and possibly cellular origins, is stabilized by RNA. We propose that structural RNA molecules mediate ORC recruitment at some cellular and viral origins, similar to OriP.


Efficiency of wastewater treatment facilities: The influence of scale economies.
The water cycle, from catchment to discharge, is a sector that involves an important investment and operation and maintenance costs. In particular, sewage treatment is a challenge for governments because they are having to consider economic, environmental, and social aspects. Within the European Union, implementation of Directive 91/271/EEC is responsible for the location of wastewater treatment facilities in the territory, due to the requirement that all urban areas must have this infrastructure to reduce the environmental impact of treated water in water bodies. Different sizes of municipalities affect the design of each wastewater treatment plant (WWTP) and cause variations in the operation process. The presence of scale economies in this sector has a significant influence on the efficiency of the wastewater treatment process and has a direct impact on the operational costs. Based on the pursuit of economic and environmental efficiency, this analysis extends the scope of the current literature because it recommends a specific, population equivalent (p.e.) range for which it would be suitable to achieve efficiency in wastewater treatment facilities-shedding light on the open debate about scale economies in WWTPs.


High incidence of ultraviolet-B-or chemical-carcinogen-induced skin tumours in mice lacking the xeroderma pigmentosum group A gene.
Xeroderma pigmentosum (XP) is an autosomal recessive disorder characterized by a high frequency of skin cancer on sun-exposed areas, and neurological complications. XP has a defect in the early step(s) of nucleotide-excision repair (NER) and consists of eight different genetic complementation groups (groups A-G and a variant). We established XPA (group-A XP) gene-deficient mice by gene targeting of mouse embryonic stem (ES) cells. The XPA-deficient mice showed neither obvious physical abnormalities nor pathological alterations, but were defective in NER and highly susceptible to ultraviolet-B- or 9,10-dimethyl-1,2-benz[a]anthracene-induced skin carcinogenesis. These findings provide in vivo evidence that the XPA protein protects mice from carcinogenesis initiated by ultraviolet or chemical carcinogen. The XPA-deficient mice may provide a good in vivo model to study the high incidence of skin carcinogenesis in group A XP patients.


Pacemaker related tachycardias.
Three cases of pacemaker interactive tachycardia are presented. The first two are [artificial] circus movement tachycardias. In the first one the retrograde arm of the tachycardia circuit was provided by the A-V node and the antegrade arm by an atrial synchronous pulse generator. In the second case, the A-V node and, coincidentally, an A-V sequential pulse generator alternately provided the antegrade arm while the retrograde arm was by way of an accessory pathway. In the third case ventricular inhibition during A-V sequential pacing gave the paced atrial events the chance to be conducted to the ventricles with a long A-V interval. This resulted in a tachycardia with a rate of 150 bpm, instead of the programmed rate of 110 bpm.


A programmable-delay line.
A relatively simple circuit is described which delays audio signals in 5 microseconds steps from 0 microsecond to 4000 microseconds. Delays are programmed via twelve TTL-level data lines. The magnitude response is flat and the phase response is linear from DC to 5 kHz. The gain of the circuit is fixed and independent of the selected delay. Delays are accurate to within 1 microsecond of the programmed value. The device is a nice alternative to other methods which have diverse shortcomings.