A nomogram predicting the severity of COVID-19 based on initial clinical and radiologic characteristics.
Aim: This study aimed to build an easy-to-use nomogram to predict the severity of COVID-19. Patients & methods: From December 2019 to January 2020, patients confirmed with COVID-19 in our hospital were enrolled. The initial clinical and radiological characteristics were extracted. Univariate and multivariate logistic regression were used to identify variables for the nomogram. Results: In total, 104 patients were included. Based on statistical analysis, age, levels of neutrophil count, creatinine, procalcitonin and numbers of involved lung segments were identified for nomogram. The area under the curve was 0.939 (95% CI: 0.893-0.984). The calibration curve showed good agreement between prediction of nomogram and observation in the primary cohort. Conclusion: An easy-to-use nomogram with great discrimination was built to predict the severity of COVID-19.


The role of inflammation in hypoxic pulmonary hypertension: from cellular mechanisms to clinical phenotypes.
Hypoxic pulmonary hypertension (PH) comprises a heterogeneous group of diseases sharing the common feature of chronic hypoxia-induced pulmonary vascular remodeling. The disease is usually characterized by mild to moderate pulmonary vascular remodeling that is largely thought to be reversible compared with the progressive irreversible disease seen in World Health Organization (WHO) group I disease. However, in these patients, the presence of PH significantly worsens morbidity and mortality. In addition, a small subset of patients with hypoxic PH develop "out-of-proportion" severe pulmonary hypertension characterized by pulmonary vascular remodeling that is irreversible and similar to that in WHO group I disease. In all cases of hypoxia-related vascular remodeling and PH, inflammation, particularly persistent inflammation, is thought to play a role. This review focuses on the effects of hypoxia on pulmonary vascular cells and the signaling pathways involved in the initiation and perpetuation of vascular inflammation, especially as they relate to vascular remodeling and transition to chronic irreversible PH. We hypothesize that the combination of hypoxia and local tissue factors/cytokines ("second hit") antagonizes tissue homeostatic cellular interactions between mesenchymal cells (fibroblasts and/or smooth muscle cells) and macrophages and arrests these cells in an epigenetically locked and permanently activated proremodeling and proinflammatory phenotype. This aberrant cellular cross-talk between mesenchymal cells and macrophages promotes transition to chronic nonresolving inflammation and vascular remodeling, perpetuating PH. A better understanding of these signaling pathways may lead to the development of specific therapeutic targets, as none are currently available for WHO group III disease.


Prospective analysis of antigen-specific immunity, stem-cell antigens, and immune checkpoints in monoclonal gammopathy.
Blockade of immune checkpoints (ICPs) has led to impressive responses in cancer patients. However, the impact of preexisting immunity and ICPs on the risk of malignant transformation in human preneoplasia has not been prospectively studied. We prospectively analyzed antigen-specific B/T-cell immunity, immune composition of the tumor microenvironment, and the expression of a panel of ICPs on tumor and tumor-infiltrating immune cells in 305 patients with asymptomatic monoclonal gammopathy enrolled in S0120 under the auspices of SWOG. T-cell immunity against stem-cell antigen SOX2 and preserved humoral responses at study entry independently correlated with reduced risk of progression to clinical myeloma. Among the ICPs analyzed, expression of programmed death-ligand 1 (PD-L1) on tumor and infiltrating T cells correlated with increased risk of clinical malignancy, and blockade of this pathway boosted anti-SOX2 immunity in culture. These data suggest that stem-cell antigens and PD-L1 may be targeted for immunoprevention of myeloma. This trial was registered at www.clinicaltrials.gov as #NCT00900263.


Relatedness in the post-genomic era: is it still useful?
Relatedness is a fundamental concept in genetics but is surprisingly hard to define in a rigorous yet useful way. Traditional relatedness coefficients specify expected genome sharing between individuals in pedigrees, but actual genome sharing can differ considerably from these expected values, which in any case vary according to the pedigree that happens to be available. Nowadays, we can measure genome sharing directly from genome-wide single-nucleotide polymorphism (SNP) data; however, there are many such measures in current use, and we lack good criteria for choosing among them. Here, we review SNP-based measures of relatedness and criteria for comparing them. We discuss how useful pedigree-based concepts remain today and highlight opportunities for further advances in quantitative genetics, with a focus on heritability estimation and phenotype prediction.


TRPM7 Regulates AKT/FOXO1-Dependent Tumor Growth and Is an Independent Prognostic Indicator in Renal Cell Carcinoma.
Transient receptor potential melastatin 7 (TRPM7) is important for the tumorigenesis and progression of several cancers. However, little is known about TRPM7 expression and its clinical significance in clear cell renal cell carcinoma (ccRCC). The expression dynamics of TRPM7 was examined in a clinical cohort of RCC specimens by qPCR, immunoblotting, and IHC staining. A series of in vitro and in vivo assays were performed to elucidate the function of TRPM7 in RCC and the underlying mechanisms. For the first time, results demonstrate that TRPM7 expression is markedly higher in RCC cell lines and clinical samples and had a positive correlation with T status, tumor size, and poor patients' overall survival and progression-free survival. Preclinical studies using multiple RCC cells and a mouse model indicate that TRPM7 promotes cell proliferation and colony formation in vitro and tumor growth in vivo Mechanistically, TRPM7 promotes AKT phosphorylation, leading to repression of the FOXO1 expression and transcriptional activity. Moreover, luciferase reporter assays demonstrate that miR-129-3p directly targets the 3'-UTR of TRPM7 and acts as a negative regulator of TRPM7. These findings reveal an important role for TRPM7 in the regulation of RCC growth and represent a novel prognostic biomarker for this disease.Implications: TRPM7 is an independent prognostic indicator in RCC, and targeting the TRPM7 signaling pathway may be a novel therapeutic approach for the treatment of RCC. Mol Cancer Res; 16(6); 1013-23. ©2018 AACR.


Recent progress in radiofrequency ablation therapy for hepatocellular carcinoma.
In order to attain better ablation and more effective management of hepatocellular carcinoma (HCC), new approaches and devices in radiofrequency ablation (RFA) therapy were presented and discussed in a workshop at the 50th Annual Meeting of the Liver Cancer Study Group of Japan. A novel bipolar RFA apparatus was introduced in Japan in January 2013. Hundreds of subjects with HCC were treated with multipolar RFA with varied devices and plans. Among these, no-touch ablation was one of the most useful procedures in the treatment of HCC with the apparatus. In RFA therapy, a few assisting devices and techniques were applied for convenience and improvement of the thermal ablation procedure. Contrast-enhanced ultrasonography and three-dimensional fusion imaging technique using volume data of CT or MRI could improve exact targeting and shorten the treatment time for RFA procedures under ultrasonographic guidance. A more complicated method using a workstation was also reported as being helpful in planning the ablated shape and volume in multineedle RFA. The effective use of sedatives and antianalgesics as well as a novel microwave apparatus with a cooled-tip electrode was also discussed.


A bifactor model of intolerance of uncertainty in undergraduate and clinical samples: Do we need to reconsider the two-factor model?
The theorized role that intolerance of uncertainty (IU) plays in the acquisition, maintenance, and treatment of multiple emotional disorders underscores the importance of valid assessment tools. Research using the Intolerance of Uncertainty Scale-Short form (IUS-12) has conceptualized IU along 2 dimensions, namely, prospective IU and inhibitory IU. However, recent research has cast doubt on the separability of these dimensions. The aim of the current study was to evaluate the fit of competing measurement models of the IUS-12 in separate undergraduate (N = 506) and clinical (N = 524) samples. Unidimensional, correlated 2-factor, and bifactor models were tested using confirmatory factor analysis. The results of both studies supported a bifactor model consisting of a strong general IU factor. The general IU factor explained the majority of unique variance in the IUS-12, and suggested that a total score is generally appropriate for assessing IU. The general IU factor was most strongly and consistently associated with symptoms of multiple disorders. The inhibitory IU group factor was more weakly associated with most symptom measures in the clinical sample, but only with social phobia symptoms in the undergraduate sample. The prospective IU group factor was only separable from the general IU factor in the undergraduate sample, and did not explain unique variance in disorder symptoms. (PsycINFO Database Record


Serum and urinary SOD3 in patients with type 2 diabetes: comparison with early chronic kidney disease patients and association with development of diabetic nephropathy.
Extracellular superoxide dismutase 3 (SOD3), one member of the antioxidant defense system and a superoxide scavenger, has been noted to be downregulated in the kidneys of diabetic mice and is characterized by a heparin-binding domain that can anchor the protein to the endothelium and extracellular matrix. The association of the serum and urinary SOD3 levels with diabetic nephropathy in different stages has never been evaluated. It remains unclear how urinary SOD3 changes in different renal diseases. We recruited 98 Taiwanese patients with type 2 diabetes and 10 patients with early chronic kidney disease (CKD) into this study. Biochemical analyses were performed, including evaluation of the serum SOD3, urinary SOD3, urinary albumin, urinary vascular endothelial growth factor (VEGF), and urinary angiotensinogen (ANG). The Kruskal-Wallis rank sum test was used to compare various parameters among the three groups of patients: early CKD, diabetes alone, and diabetes with CKD. Results showed that lower serum and urinary SOD3 levels were observed in the group of patients with diabetes alone. Higher serum and urinary SOD3 levels were observed in the group of patients with diabetes and CKD, which had higher albuminuria and serum creatinine levels. The serum SOD3 levels were significantly positively correlated with renal function, according to the serum creatinine level. The urinary levels of SOD3 were significantly correlated with other urinary biomarkers such as urinary ANG and VEGF. Furthermore, albuminuria can positively predict the serum SOD3 level for the ratio of urinary albumin to urinary creatinine (ACR) >1,190.769 mg/g and the urinary SOD3 level for ACR ≥300 mg/g.


RNA editing in transcripts of the mitochondrial genes of the insect trypanosome Crithidia fasciculata.
With the aid of cDNA and RNA sequence analysis, we have determined to what extent transcripts of mitochondrial maxicircle genes of the insect trypanosome Crithidia fasciculata are altered by RNA editing, a novel mechanism of gene expression which operates via the insertion and deletion of uridine residues. Editing of cytochrome c oxidase (cox) subunit II and III transcripts and of maxicircle unidentified reading frame (MURF) 2 RNA is limited to a small section and results in the creation of a potential AUG translational initiation codon (coxIII, MURF2) or the removal of a frameshift (coxII). No differences with the genomic sequences were observed in the remainder of these RNAs. Surprisingly, NADH dehydrogenase subunit I transcripts were completely unedited in the coding region, implying that an AUG translational initiation codon is absent. The partial ribosomal RNA sequences determined also conform to the gene sequences. Together these results lead to the conclusion that the unusual sequences predicted by the protein and rRNA genes must indeed be present in the gene products. Editing also occurred in the poly(A) tail of RNAs from all protein genes, including those that are unedited in the coding region. The tails display a large variation in AU sequence motifs. Finally, some cDNAs contained sequences absent from both the DNA and the edited RNA. Some of these may represent intermediates in the RNA editing process. We argue, however, that long runs of T may be artefacts of cDNA synthesis.


Products of Lactobacillus delbrueckii subsp. bulgaricus Strain F17 and Leuconostoc lactis Strain H52 Are Biopreservatives for Improving Postharvest Quality of 'Red Globe' Grapes.
'Red Globe' table grapes are large, edible, seeded fruit with firm flesh that tastes good, but can have poor postharvest shelf-life. This study was conducted to explore the effects of products of Lactobacillus delbrueckii subsp. bulgaricus strain F17 and Leuconostoc lactis strain H52 on 'Red Globe' table grapes for the enhancement of shelf-life and improvement of grape quality characteristics during postharvest storage. Strains F17 and H52 were isolated from traditional fermented yak milk obtained in the Qinghai-Tibetan Plateau. Samples from untreated and treated grapes were analyzed for physicochemical, biochemical, and microbiological properties (weight loss, decay rate, pH, total soluble solids content, titratable acidity, total phenols, sensory evaluation, and microbial growth) for 20 days. The results demonstrated that supernatants from both strains significantly reduced weight loss, decay rate, aerobic mesophilic bacteria, and coliform bacteria counts; delayed maturity and senescence of table grapes; and reduced titratable acidity and total phenols. However, the supernatant of strain F17 was more effective and resulted in better sensory evaluations and had a significant inhibitory effect on yeast and molds by day 5. Meanwhile, the supernatant from strain H52 had a significant inhibitory effect on fungi over the whole storage period. In addition, the results of the Pearson correlation analysis suggested that weight loss, decay rate, total soluble solids content, and microorganisms were highly correlated with the sensory evaluation data and quality of postharvest grapes when treated with the products of strain F17. On the basis of these data and sensory organoleptic qualities, the supernatant containing products from strain F17 had the best potential as a biopreservative to improve the postharvest quality of 'Red Globe' table grapes.


The Health System Costs of Postabortion Care in Senegal.
Unsafe abortion is common in Senegal, but postabortion care (PAC) is not accessible to some women who need it, and the cost to the health care system of providing PAC is unknown. The cost to Senegal's health system of providing PAC in 2016-at existing service levels and if access were hypothetically expanded-was estimated using the Post-Abortion Care Costing Methodology, a bottom-up, ingredients-based approach. From September 2016 to January 2017, face-to-face interviews were conducted with PAC providers and facility administrators at a national sample of 41 health facilities to collect data on the direct and indirect costs of care provision, as well as the fees charged to patients. A sensitivity analysis was conducted to examine the precision of the results. In total, 1,642 women received PAC at study facilities in 2016, which translates to 18,806 women receiving PAC nationally. Public facilities provided nearly all services. The average cost per patient at study facilities was US$26.68; nationally, the estimated cost was US$24.72. The estimated total national cost of providing PAC at existing levels was US$464,928; direct costs accounted for more than three-quarters of the cost. Charges to PAC patients amounted to 20% of all incurred costs. If service provision had been expanded to meet all PAC needs, estimated total costs to the health system would have been US$804,518. The annual costs of PAC are substantial in Senegal. Greater investment in ensuring access to contraceptives could lower these costs by reducing the number of unintended pregnancies that often lead to unsafe abortion.


Defining genetically meaningful language and personality traits in relatives of individuals with fragile X syndrome and relatives of individuals with autism.
Substantial phenotypic overlap exists between fragile X syndrome (FXS) and autism, suggesting that FMR1 (the gene causing FXS) poses a significant risk for autism. Cross-population comparisons of FXS and autism therefore offer a potentially valuable method for refining the range of phenotypes associated with variation in FMR1. This study adopted a broader phenotype approach, focusing on parents who are at increased genetic liability for autism or FXS. Women who were carriers of FMR1 in its premutation state were compared with mothers of individuals with autism, and controls in an attempt to determine whether subtle features of the broad autism phenotype may express at elevated rates among FMR1 premutation carriers. The principal personality and language features comprising the broad autism phenotype (i.e., rigid and aloof personality, and particular patterns of pragmatic language use) were assessed among 49 premutation carriers who were mothers of individuals with FXS, 89 mothers of individuals with autism, and 23 mothers of typically developing individuals. Relative to controls, the autism and premutation parent groups showed elevated rates of certain personality and language characteristics of the broad autism phenotype. Findings suggest partially overlapping personality and language profiles among autism and premutation parent groups, with rigid personality style and patterns of pragmatic language use emerging as features most clearly shared between groups. These results provide further evidence for the overlap of autism and FXS, and may implicate FMR1 in some of the subtle features comprising the broad autism phenotype.


Thriving beyond survival: understanding utilization of perinatal health services as predictors of birth registration: a cross-sectional study.
There are an estimated 35 million unregistered children in Indonesia. To understand ways to best leverage existing health system-related resources and ensure greater protective measures for these vulnerable children, this study explores the predictive relationship between the utilization of perinatal health services and birth certificate ownership in two Indonesian provinces. This study employed a cross-sectional design with interviewer-administered household surveys to heads of households in West Nusa Tenggara and East Nusa Tenggara from May to July of 2013. The primary outcome of interest was birth certificate ownership among children under the age of 5 years old. Bivariate and multivariable regression analyses using Generalized Estimating Equations (GEE) considered a set of covariates that represented child and household socio-demographic characteristics along with health services utilization variables during pregnancy and post-pregnancy periods. 389 heads of households were interviewed, yielding data on a sample of 451 children under the age of 5. Fewer than 28% of children in this sample possessed a birth certificate. Nearly 57% (n = 259) of children were delivered in a clinical facility, though only 36% (n = 93) of these were legally registered. Of children born in the home (n = 194), registration dropped to 16% (n = 31). Adjusted analyses accounting for socio-demographic factors suggest that children born in a clinic facility (AOR = 2.33, 95% CI: 1.27, 4.33), hospital (AOR = 2.38, 95% CI: 1.12, 5.09), or in the presence of a skilled birth attendant (AOR = 2.35, 95% CI: 1.31, 4.23) were significantly more likely to be registered. Children whose mothers sought post-natal care were 2.99 times more likely to possess a birth certificate (AOR = 2.99, 95% CI: 1.1, 7.57). Pre-natal care was not associated with birth registration. These findings suggest that use of perinatal health services increases the likelihood of registering a child's birth despite a lack of formal integration of vital registration with the health sector. Formally leveraging existing community-based health workers and perinatal services may serve to further increase registration rates in hard to reach areas of Indonesia.


Who wins in the status games? Violence, sexual violence, and an emerging single standard among adolescent women.
Throughout U.S. history, women have changed their sexual behaviors in response to, or as actors affecting, economic, political, and legal imperatives; to preserve health; to promote new relationship, identity or career paths; to assert a set of values; as a result of new reproductive technologies; or to gain status. In adjusting to pressures or goals, women have not always acted, or been able to act, in the interests of their own health, identity, or status. As this article will demonstrate, women, in the short or long run, may attempt to preserve status at the cost of other values such as health. This may occur through conscious and critical choice or through less conscious processes in reaction to relatively larger forces whose impact has not been critically analyzed. With the awareness in the 1980s in the United States of an emergent and incurable sexually transmissible infection, HIV, it would have been anticipated that a new sexual caution may have appeared. Yet, across several research projects in the late 1990s and into the 21st century, as our research team interviewed youth in a high HIV seroprevalence neighborhood in New York City about HIV prevention, we began to hear that a substantial minority of young women and men were participating in social settings for sexual behavior that (1) put youth at risk for HIV; (2) appeared to be motivated by acquisition of status ("props," "points"); and (3) offered few ways for women to win in these status games. We estimate from one random dwelling unit sample that about one in eight youth have been present in these settings and half of them have participated in risky sexual behavior in such settings. The settings are often characterized by men's publicly offhand attitudes toward sexual encounters, are organized around men's status maintenance, and evidence peer pressures that are poorly understood by both young men and women participants. To regain status, some women participants have adopted attitudes more characteristic of men.


Immunization of bull calves with a GnRH analogue-human serum albumin conjugate: effect of conjugate dose, type of adjuvant and booster interval on immune, endocrine, testicular and growth responses.
Bull calves were immunized with GnRH analogue-human serum albumin (HSA-Cys-Gly-GnRH) conjugate to determine the effects of dose, adjuvant type and interval between primary and booster injections on plasma testosterone and LH concentrations, and testes and body growth. Friesian bull calves aged between 8 and 10 weeks (n = 72) were blocked according to age and weight and, within block, randomly assigned to 12 treatment combinations (n = 6 per treatment combination) in a 3 x 2 x 2 factorial plan. Main effects were (i) conjugate dose (0.0, 0.1 or 1.0 mg HSA-Cys-Gly-GnRH), (ii) adjuvant (diethylaminoethyl-dextran or non-ulcerative Freund's adjuvant), and (iii) interval between primary (day 0) injection and booster injection (day 28 or 56). Plasma testosterone and LH concentrations and antibody titres were determined in blood samples collected at 14 day intervals during the experiment (140 days). Testicular measurements were taken in situ every 28 days. Antibody titres (% binding at 1:160 dilution) were > or = 10% 28 days after booster injection and remained high for 140 days in 47 of 48 GnRH-immunized bulls. The mean titre was higher (P < 0.05) in response to the 1.0 mg dose compared with the 0.1 mg dose (37.7% versus 29.6% binding, respectively; pooled SED 2.55%). Mean LH and testosterone concentrations were reduced (P < 0.05) in immunized animals compared with controls. However, the 1.0 mg dose decreased mean testosterone concentrations by a greater extent (P < 0.001) than either the 0.1 mg or 0.0 mg doses. Testes length and depth, and scrotal circumference were decreased (P < 0.001) in immunized animals compared with controls; however, the 1.0 mg dose decreased (P < 0.001) testes parameters to the greatest extent. There was no effect of conjugate dose on average daily gain in body mass. It is concluded that (i) dose of conjugate, type of adjuvant and interval between primary and booster injections affected antibody titres, (ii) the use of 0.1 or 1.0 mg of HSA-Cys-Gly-GnRH decreased LH and testosterone concentrations, and testicular development throughout the experiment, without adversely affecting body growth, and (iii) an effective protocol is 1.0 mg GnRH-HSA conjugate, given in the adjuvant diethylaminoethyl dextran, with a primary-booster interval of 56 days.


Studies on quantitative aspects of the transmission of Wuchereria bancrofti.
Feeding experiments with Anopheles gambiae and Culex fatigans infected with Wuchereria bancrofti showed that the mosquito females were losing about 20% of their worm burden when they were feeding on a blood chamber as well as on the guinea pig. 6.6% of all mature larvae found in the mosquitoes succeeded in entering the final host. A striking high infection rate was observed in those mosquitoes which refused to feed on a guinea pig. These mosquitoes have also to be considered when the loss of filarial larvae is calculated. Furthermore the experiments showed, that only very few larvae of Wuchereria bancrofti get lost when the mosquitoes are feeding only on sugar water solution.


Near-Quantum-Noise Axion Dark Matter Search at CAPP around 9.5 μeV.
We report the results of an axion dark matter search over an axion mass range of 9.39-9.51 μeV. A flux-driven Josephson parametric amplifier (JPA) was added to the cryogenic receiver chain. A system noise temperature of as low as 200 mK was achieved, which is the lowest recorded noise among published axion cavity experiments with phase-insensitive JPA operation. In addition, we developed a two-stage scanning method which boosted the scan speed by 26%. As a result, a range of two-photon coupling in a plausible model for the QCD axion was excluded with an order of magnitude higher in sensitivity than existing limits.


The etiology of oxidative stress in the various species of animals, a review.
Oxidative stress is the consequence of an imbalance of pro-oxidants and antioxidants leading to cell damage and tissue injury. The exhaustion of antioxidant systems is one of the reasons for the occurrence of oxidative stress, which results in avalanche production of reactive oxygen species (ROS) or free radicals. High oxidative stress is common in organs and tissues with high metabolic and energy demands, including skeletal and heart muscle, liver and blood cells. Stress arises in animals in response to unavoidable or adverse environmental conditions. In the external environment, which affects the body of the cow, there are four main groups of stressors: physical, chemical, biological and psychological. Physical stressors include fluctuations in ambient temperature as well as mechanical injuries. High ambient temperature is one of the factors affecting the productivity of cows. Biological stressors are conditioned by errors and irregularities in habits. Both of these phenomena have an adverse impact on both the resistance of animals and fertility and are the etiological agent of oxidative stress. Various mechanisms may be responsible for metal-induced oxidative stress: direct or indirect generation of ROS, depletion of glutathione and inhibition of antioxidant enzymes are well known for all redox-active and redox-inactive metals.


Measurement properties of the calendar of premenstrual experience in patients with premenstrual syndrome.
To assess the reliability and factor structure of the Calendar of Premenstrual Experiences (COPE) in premenstrual syndrome (PMS) patients. Healthy women diagnosed with PMS (N = 215) completed daily diaries assessing 22 PMS behavioral and physical symptoms over two consecutive months. Internal consistency (alpha) was high (.93-.94) for the COPE total score and behavioral subscale score and moderately high (.79) for the physical subscale score. Test-retest correlations produced lower estimates of reliability (.55-.59). Four factors, accounting for 64% of the total variance, were extracted: mood symptoms, somatic/cognitive symptoms, appetitive symptoms and fluid retention symptoms. Symptom reports increased in consecutive luteal phases for three of the four factors; however, the factor structure remained consistent in consecutive months. The COPE diary is a reliable instrument for identifying fluctuations in behavioral and physical symptoms during the luteal phase, and PMS symptoms can be reliably conceptualized within four factors. Symptom expression may increase in response to daily self-monitoring.


Deep learning and social network analysis elucidate drivers of HIV transmission in a high-incidence cohort of people who inject drugs.
Globally, people who inject drugs (PWID) experience some of the fastest-growing HIV epidemics. Network-based approaches represent a powerful tool for understanding and combating these epidemics; however, detailed social network studies are limited and pose analytical challenges. We collected longitudinal social (injection partners) and spatial (injection venues) network information from 2512 PWID in New Delhi, India. We leveraged network analysis and graph neural networks (GNNs) to uncover factors associated with HIV transmission and identify optimal intervention delivery points. Longitudinal HIV incidence was 21.3 per 100 person-years. Overlapping community detection using GNNs revealed seven communities, with HIV incidence concentrated within one community. The injection venue most strongly associated with incidence was found to overlap six of the seven communities, suggesting that an intervention deployed at this one location could reach the majority of the sample. These findings highlight the utility of network analysis and deep learning in HIV program design.


Nutritional and Micronutrient Care of Bariatric Surgery Patients: Current Evidence Update.
The continued success of bariatric surgery to treat obesity and obesity-associated metabolic conditions creates a need for a strong understanding of clinical nutrition both before and after these procedures. Surgically induced alteration of gastrointestinal physiology can affect the nutrition of individuals, especially among those who have undergone malabsorptive procedures. While uncommon, a subset of patients may develop protein-calorie malnutrition. In these cases, nutrition support should be tailored to the severity of malnutrition. Among all patients who undergo bariatric surgery, high rates of micronutrient deficiencies have been observed. To mitigate these deficiencies, empiric supplementation with multivitamins, calcium citrate, and vitamin D is generally recommended. Periodic surveillance should be performed for commonly deficient micronutrients, including thiamin (B1), folate (B9), cobalamin (B12), iron, and vitamin D. Following Roux-en-Y gastric bypass, serum levels of copper and zinc should also be monitored. In addition, lipid-soluble vitamins should be monitored following biliopancreatic diversion with/without duodenal switch.


Resistive-pulse studies of proteins and protein/antibody complexes using a conical nanotube sensor.
There is increasing interest in using nanopores in synthetic membranes as resistive-pulse sensors for molecular and macromolecule analytes. In general, this method entails measuring current pulses associated with translocation of the analyte through the nanopore sensor element. A key challenge for this sensing paradigm is building selectivity into the protocol so that the current pulses for the target analyte can be distinguished from current pulses for other species that might be present in the sample. We show here that this can be accomplished with a protein analyte by adding to the solution an antibody that selectively binds the protein. We demonstrate this concept using bovine serum albumin (BSA) and a Fab fragment from a BSA-binding polyclonal antibody. Because the complex formed upon binding of the Fab to BSA is larger than the free BSA molecule, the current-pulse signature for the BSA/Fab complex can be easily distinguished from the free BSA. Furthermore, the BSA/Fab pulses can be easily distinguished from the pulses obtained for the free Fab and from pulses obtained for a control protein that does not bind to the Fab. Finally, we also show that the current-pulse signature for the BSA/Fab complex can provide information about the size and stoichiometry of the complex.


Hand Nicotine and Cotinine In Children Exposed to Cigars: A Pilot Study.
Past research has not examined secondhand and thirdhand smoke (THS) exposure in children of cigar smokers. We examined hand nicotine and cotinine levels in children of cigar smokers to explore the contribution of cigar smoke to tobacco smoke exposure (TSE). Participants were children (N = 24; mean (SD) age = 6.5 (3.6) years) whose parents smoked cigars only or poly-used cigars and/or cigarettes. Primary outcomes were hand nicotine and urinary cotinine levels. All children had detectable hand nicotine (range: 7.6-312.5ng/wipe) and cotinine (range: 0.3-100.3ng/ml). Positive correlations were found between hand nicotine and cotinine (r = 0.693, p = .001), hand nicotine and parents who also smoked cigarettes (r = 0.407, p = .048), and hand nicotine and number of smokers around the child (r = 0.436, p = .03). Hand nicotine (r = -0.464, p = .02), but not cotinine (r = -0.266, p = .26), was negatively correlated with child age. Multiple regression results indicated a positive association between hand nicotine and cotinine (p = .002; semi-partial r2 = 0.415), irrespective of child age. The significant association of hand nicotine with urinary cotinine suggests that THS pollution should be assessed in evaluating children's overall TSE to cigars and other tobacco products, and hand nicotine may be a proxy for overall TSE. Younger children may have increased THS pollutant uptake.


Long double-stranded RNA-mediated RNA interference and immunostimulation: long interfering double-stranded RNA as a potent anticancer therapeutics.
In most applications, small interfering RNAs are designed to execute specific gene silencing via RNA interference (RNAi) without triggering nonspecific responses such as immunostimulation. However, in anticancer therapeutics, immunostimulation combined with specific oncogene silencing could be beneficial, resulting in the synergistic inhibition of cancer cell growth. In this study, we report an immunostimulatory long double-stranded RNA (dsRNA) structure with the ability to trigger RNAi-mediated specific target gene silencing, termed as long interfering dsRNA (liRNA). liRNA targeting Survivin mRNA not only efficiently and specifically triggered target gene silencing via RNAi, but also stimulated the protein kinase R pathway to induce the expression of interferon β. As a result, the ability of Survivin-targeting liRNA to inhibit cancer cell growth was superior over conventional small interfering RNA or nontargeting dsRNA structures. Our results thus provide a simple yet efficient dual function immunostimulatory RNAi-triggering structure, which is potentially applicable for the development of anticancer therapeutics.


The effect of glycerol-containing peritoneal dialysis fluid on peritoneal macrophage function in vivo.
Though glucose is universally applied as osmotic agent in CAPD, there is great interest in the use of alternative osmotic agents. Glycerol-containing peritoneal dialysis fluids (G-PDF) have been used in an attempt to minimize the metabolic effects of long-term exposure to glucose, especially in patients with diabetes. Since data were lacking, we studied the effect of G-PDF on peritoneal macrophage (PMO) function. In a randomized cross-over setting eight stable diabetic CAPD patients performed the third and fourth exchange of the day with either G-PDF or with glucose-containing PDF (D-PDF) of comparable osmolality. The next day the patients who had used G-PDF were switched to D-PDF and vice versa. PMO were isolated from the effluents and tested for their phagocytic capacity and chemiluminescence response. No differences were encountered in total and differential white cell counts between G-PDF and D-PDF effluents. PMO phagocytic capacity for both S. epidermidis (SE) and E. coli (EC) was significantly depressed after the instillation of G-PDF as compared to D-PDF (SE: 52 +/- 2.7 vs 69 +/- 5.0%, p less than 0.02, and EC: 44 +/- 5.7 vs 63 +/- 6.7%, p less than 0.02). The same held true for peak chemiluminescence response (5.3 +/- 1.36 vs 7.2 +/- 1.43% of control cells, p less than 0.005). Thus, G-PDF may compromise PMO function in vivo more than D-PDF despite its more favourable metabolic profile as compared to D-PDF for diabetic patients.


Cost-effectiveness of transcatheter aortic valve implantation compared to surgical aortic valve replacement in the intermediate surgical risk population.
The recent PARTNER S3i trial compared transcatheter aortic valve implantation (TAVI) using the third-generation SAPIEN 3 device to surgical aortic valve replacement (SAVR) in intermediate-risk patients with severe symptomatic aortic stenosis. Using data from PARTNER S3i, we performed a contemporary cost-effectiveness analysis of current-generation TAVI versus SAVR from the Australian healthcare system perspective. A Markov model with monthly cycles and a ten-year horizon was constructed to estimate costs, life-years and quality adjusted life-years (QALYs) associated with TAVI and SAVR. Efficacy inputs were derived from the PARTNER S3i study. Costs were estimated from published sources. Deterministic and probabilistic sensitivity analyses were performed to assess model uncertainty. TAVI was found to have higher immediate procedural costs than SAVR, driven primarily by the cost of the transcatheter valve. This was offset by a shorter length of hospitalisation following TAVI, such that the combined cost of initial procedure and hospitalisation was lower in TAVI compared to SAVR. With 5% annual discounting, total costs over ten-years were $50,515 AUD in TAVI and $60,144 AUD in SAVR, and TAVI was found to produce 0.33 more life years and 0.31 more QALYs than SAVR. Thus, from a health economic perspective, TAVI was dominant compared to SAVR. Results were robust to sensitivity analyses, with TAVI being dominant in 68% of 10,000 Monte Carlo iterations and cost-effective in 92% of iterations at a willingness-to-pay threshold of $50,000/QALY gained. TAVI is likely to be highly cost-effective compared to SAVR in intermediate-risk patients with severe aortic stenosis.


Arthroscopic Biological Augmentation With Subacromial Bursa for Bursal-Sided Partial-Thickness Rotator Cuff Tears.
Augmentation with subacromial bursa has not been fully established in bursal-sided partial-thickness rotator cuff tears (PT-RCTs). To compare the results of acromioplasty + arthroscopic debridement versus acromioplasty + augmentation with subacromial bursa for Ellman type 2 PT-RCTs involving 25% to 50% of the tendon surface area. Cohort study; Level of evidence, 3. Included were 40 patients (mean age, 47.8 years) with Ellman type 2 PT-RCTs whose symptoms did not regress despite 3 months of nonoperative treatment. The patients underwent either acromioplasty + debridement (group A; n = 18) or acromioplasty + augmentation (group B; n = 22). Outcome scores (visual analog scale [VAS] pain score, Constant-Murley score [CMS], and American Shoulder and Elbow Surgeons [ASES] score) were obtained preoperatively and at 6, 12, and 18 months postoperatively. Magnetic resonance imaging (MRI) scans performed at 6 months postoperatively were used to determine the integrity and state of healing. There were no significant differences between groups A and B in preoperative VAS, CMS, or ASES scores, and patients in both groups saw significant improvement at each follow-up time point on all 3 outcome scores (P = .001 for all). Scores on all 3 outcome measures were significantly better in group B than group A at each postoperative time point (P < .05 for all). Postoperative MRI scans revealed persistent partial tears in 5 of 18 patients in group A compared with 2 of 22 patients in group B (P < .05). Conversion to full-thickness tear (3/18 patients) was seen only in group A. Patients who underwent biological augmentation of their PT-RCTs had improved outcome scores compared with those treated with acromioplasty and debridement alone.


Synthesis and structure-activity relationships of beta- and alpha-piperidine sulfone hydroxamic acid matrix metalloproteinase inhibitors with oral antitumor efficacy.
alpha-Piperidine-beta-sulfone hydroxamate derivatives were explored that are potent for matrix metalloproteinases (MMP)-2, -9, and -13 and are sparing of MMP-1. The investigation of the beta-sulfones subsequently led to the discovery of hitherto unknown alpha-sulfone hydroxamates that are superior to the corresponding beta-sulfones in potency for target MMPs, selectivity vs MMP-1, and exposure when dosed orally. alpha-Piperidine-alpha-sulfone hydroxamate 35f (SC-276) was advanced through antitumor and antiangiogenesis assays and was selected for development. Compound 35f demonstrates excellent antitumor activity vs MX-1 breast tumor in mice when dosed orally as monotherapy or in combination with paclitaxel.


[A clinical study on the morphological restoration of the spinal cord in cervical myelopathy by CT-myelography and ultrasonography].
The relationship between the pattern of spinal restoration and the degree of clinical improvements after posterior decompression for cervical myelopathy was evaluated by CT-myelography (CTM) and ultrasonography. On the basis of preliminary comparison between CTM and ultrasonographic images, the cross-sectional area, sagittal diameter, and frontal diameter of the cervical spinal cord were determined by CTM (before and 1 month after decompression) and ultrasonography (immediately after decompression during the operation). The spinal cord restoration occurred quickly just after decompression and then more slowly, and its pattern was classified into 4 types: Type 1 for neither quick nor slow restoration; type II for only quick restoration; type III for only slow restoration; and type IV for both restorations observed simultaneously. From the degree of clinical improvement in each restoration type, slow restoration appeared to be more closely related to such improvement than quick restoration despite their morphological similarities.


Purification of cytochrome P-450 from pig testis by aniline-sepharose 4B and isoelectric focusing.
Testicular cytochrome P-450 was purified by a procedure including preparative isoelectrofocusing. The cytochrome P-450 was determined to have an isoelectric point of 6.47 on analytical isoelectric focusing. The purified cytochrome P-450 was found to be homogeneous and its molecular weight was estimated to be 52,000 on polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The carbon monoxide difference spectrum with a peak at 448 nm exhibited absorption spectrum of a typical cytochrome P-450. 284-fold purification was achieved with an yield of 10.6%. Following preparation of the microsomes, the purification is accomplished by a two-step procedure utilizing Aniline-Sepharose 4B column chromatography and preparative isoelectric focusing.


Cost effectiveness of pegfilgrastim versus filgrastim after high-dose chemotherapy and autologous stem cell transplantation in patients with lymphoma and myeloma: an economic evaluation of the PALM Trial.
Use of the recombinant human granulocyte colony-stimulating factor (rhG-CSF) filgrastim accelerates neutrophil recovery following myelosuppressive chemotherapy. Since filgrastim requires multiple daily administrations, forms of rhG-CSF with a longer half life, including pegfilgrastim, have been developed. Pegfilgrastim is safe and effective in supporting neutrophil recovery and reducing febrile neutropenia after conventional chemotherapy. Pegfilgrastim has also been successfully used to support patients undergoing peripheral blood stem cell (PBSC) transplantation for haematological malignancies. To our knowledge, no cost-effectiveness analysis (CEA) of pegfilgrastim in this setting has been published yet. We undertook a CEA to compare a single injection of pegfilgrastim versus repeated administrations of filgrastim in patients who had undergone PBSC transplantation for lymphoma or myeloma. The CEA was set in France and covered a period of 100 ± 10 days from transplant. The CEA was designed as part of an open-label, multicentre, randomized phase II trial. Costs were assessed from the hospital's point of view and are expressed in 2009 euros. Costs computation focused on inpatient, outpatient, and home care. Costs in the two arms of the study were compared using the Mann-Whitney test. When differences were statistically significant, multiple regression analyses were performed in order to identify cost drivers. Incremental cost-effectiveness ratios (ICER) were calculated for the major endpoints of the trial; i.e., duration of febrile neutropenia (absolute neutrophil count [ANC] <0.5 × 10(9)/L and temperature ≥38 °C), duration of neutropenia (ANC <1.0 × 10(9)/L and ANC <0.5 × 10(9)/L), duration of thrombopenia (platelets <50 × 10(9)/L and <20 × 10(9)/L), and days with a temperature ≥38 °C). Uncertainty around the ICER was captured by a probabilistic analysis using a non-parametric bootstrap method. 151 patients were enrolled at ten French centres from October 2008 to September 2009. The mean total cost in the pegfilgrastim arm of the study (n = 74) was <euro>25,024 (SD 9,945). That in the filgrastim arm (n = 76) was <euro>28,700 (SD 20,597). Pegfilgrastim strictly dominated filgrastim for days of febrile neutropenia avoided, days of neutropenia (ANC <1.0 × 10(9)/L) avoided, days of thrombopenia (platelets <20 × 10(9)/L) avoided, and days with temperature ≥38 °C) avoided. Pegfilgrastim was less costly and less effective than filgrastim for the number of days with ANC <0.5 × 10(9)/L avoided and the number of days with platelets <50.0 × 10(9)/L avoided. Taking uncertainty into account, the probabilities that pegfilgrastim strictly dominated filgrastim were 67 % for febrile neutropenia, 86 % for neutropenia (ANC <1.0 × 10(9)/L), 59 % for thrombopenia (platelets <20 × 10(9)/L), 86 % for temperature ≥38 °C, 32 % for neutropenia (ANC <0.5 × 10(9)/L), and 43 % for thrombopenia (platelets <50 × 10(9)/L). Conversely, the probability that filgrastim strictly dominated pegfilgrastim for neutropenia (ANC <0.5 × 10(9)/L) is 5 %. This study found no evidence that the use of pegfilgrastim is associated with greater cost in lymphoma and myeloma patients after high-dose chemotherapy and PBSC transplantation.


Identification of novel catalytic features of endo-beta-1,4-glucanase produced by mulberry longicorn beetle Apriona germari.
Mulberry longicorn beetle, Apriona germari, has been reported to produce two endo-beta-1,4-glucanases or AgEGases (accession Nos. Q6SS52 and Q5XQD1). AgEGase sequence contains catalytic motif (amino acid residues 37-48), which is the characteristic of family Glycohydrolase 45 and is identified as the substrate binding site. The application of bioinformatics approaches includes sequence analysis, structural modeling and inhibitor docking to relate the structure and function of AgEGases. We have dissected the sequence and structure of AgEGase catalytic motif and compared it with crystal structure of Humicola insolens endoglucanases V. The results show an involvement of sulfur containing amino acid residues in the active site of the enzyme. Cys residues and position of disulfide bonds are highly conserved between the two structures of endoglucanases of A. germari. Surface calculation of AgEGase structure in the absence of Cys residues reveals greater accessibility of the catalytic site to the substrate involving Asp42, a highly conserved residue. For the inhibition study, tannin-based structure was docked into the catalytic site of AgEGase using ArgusLab 4.0 and it resulted in a stable complex formation. It is suggested that the inhibition could occur through formation of a stable transition state analog-enzyme complex with the tannin-based inhibitor, as observed with other insect cellulases in our laboratory.


Effect of vaginally administered fumagillin on immunohistochemical distribution of leukemia inhibitory factor, interleukin 6, transforming growth factor beta and vascular endothelial growth factor in implantation stage endometrium of the rhesus monkey.
Intravaginal administration of an anti-angiogenic agent, fumagillin, during blastocyst implantation inhibits pregnancy establishment in a dose-related manner in the rhesus monkey. In the present study, mated female rhesus monkeys were vaginally inserted with tampons containing vehicle (group 1; n = 5) and test agent (fumagillin, 4 mg/animal; group 2; n = 6) on cycle day 20, and endometrial tissue samples were collected on cycle day 24 from all monkeys and processed for histological examination and immunohistochemical localization for LIF, IL-6, TGF-beta and VEGF. Concentrations of estradiol-17 beta, progesterone and chorionic gonadotrophin in peripheral circulation were determined. From the serum profiles of the hormones, 2 monkeys in group 1, and 1 monkey in group 2 appeared pregnant. However, endometrial morphology revealed histological evidence of pregnancy in 3 out of 6 fumagillin-treated animals. Histometric analysis of immunohistochemical staining in epithelial, stromal and vascular compartments revealed that per cent areas occupied by immunoprecipitate for the cytokines studies did not change in epithelial and stromal compartments, except that for TGF-beta which was higher (P < 0.05) in epithelial compartment in group 2. No change was observed in immunoprecipitation areas for IL-6 in epithelial, stromal and vascular compartments. On the other hand, changes (P < 0.05) for LIF, TGF-beta and VEGF were evident in the vascular compartment. It is possible that disparate responses observed in glandular, stromal and vascular compartments in implantation stage endometrium following fumagillin treatment actually caused from associated decline in progesterone concentration in peripheral circulation. It is also possible that fumagillin, an angiostatic agent, affects the synthesis and secretion of cytokines primarily in the vascular compartment of implantation stage endometrium, and thereby manifests differential responses in epithelial, stromal and vascular compartments.


Diabetes mellitus and immunity.
The present report discusses the immunogenic properties of insulin: the factors upon which immunogenicity depends, the characteristics of insulin antibodies, clinical aspects (insulin allergy, immunologic insulin resistance, lipodystrophy, etc.), as well as the significance of highly purified insulin products. The authors then review the role of autoimmunity in the etiopathogenesis of the diabetic disease as results from the association of diabetes with other autoimmune diseases, lymphocytic islet cell infiltration, phenomena of cell mediated and humoral mediated autoimmunity (islet cell antibodies). The present pathogenetic model of insulin-dependent diabetes (type 1) is marked by the predominance of these aspects. The last part of the report concerns immunologic functions in diabetics and the question of immune complexes.


A kinetic method to evaluate the two-state character of solvent-induced protein denaturation.
We present a kinetic method to determine the concentration of native molecules in protein folding transitions. It is based on the observation that frequently native protein molecules unfold slowly when transferred to unfolding conditions, whereas folding intermediates unfold rapidly. The fraction of native molecules in a folding transition can thus be determined by kinetic unfolding assays in a two-step procedure. Aliquots of the protein are first equilibrated at different concentrations of denaturant and then transferred to constant unfolding conditions to determine the amplitude of unfolding. This amplitude is a direct measure for the concentration of native molecules in the sample. The two-state character of a solvent-induced unfolding transition can thus be examined. When the fractional change of a spectral property in a transition follows the decrease in the concentration of the native molecules, as measured by the unfolding assays, then the presence of intermediates that differ from the unfolded protein in this property can be definitely excluded. This test complements the calorimetric test for intermediates in thermal unfolding transitions. By using this method, we show that the NaCl-induced folding transition of the reduced and carboxymethylated form of a variant of ribonuclease T1 is well described by the two-state approximation. In the unfolding of apo-alpha-lactalbumin, the measured profile for the native protein coincides with the fluorescence-detected transition, but not with the transition that is monitored by amide circular dichroism. This confirms that a partially folded intermediate is present in the folding transition of apo-alpha-lactalbumin.


Health-related quality of life in a multiethnic sample of breast cancer survivors.
Little is known about the experiences of women from varying ethnic groups following treatment for breast cancer. This study provides a comprehensive description of health-related quality of life (HRQL) and identifies problem areas and predictive factors for a multiethnic sample. Six hundred twenty-one breast cancer survivors from 2 major cities participated within 5 years of their diagnosis. Participants were African Americans, Latinas, Asian Americans, and Whites. Patients filled out questionnaire packets comprising standardized instruments related to HRQL, psychological adjustment, cancer-related treatment, and demographic variables. Data were analysed using 2 methods: (a) observation of findings prior to controlling for demographic and treatment variables and (b) observation of findings after controlling for variables confounded with ethnicity. Findings indicate that most women experienced good HRQL. Group differences revealed that African Americans found more meaning in life as a result of having breast cancer, and Latinas reported more physical symptoms. Age predicted aspects of HRQL for African Americans and Whites. This study comprehensively assessed HRQL following breast cancer for ethnic minority women. Most breast cancer survivors in this study reported levels of HRQL comparable to established norms. However, some quality of life impediments surfaced in particular groups. Researchers should not assume that predictive models of breast cancer HRQL are the same across ethnic groups.


Therapy for anomia in semantic dementia.
Semantic dementia is a commonly accepted term for a language disorder resulting from neurodegenerative changes due to frontotemporal dementia. An intervention program was designed to halt and/or decelerate the effects of progressive anomia in AK, a 63-year-old female with semantic dementia. Pictorial stimuli were selected and labeled with their respective names and a description most relevant to AK's experience. Daily homework assignments were carried out, during which AK looked at the picture, read the label aloud, and read the description. Positive short-term effects of treatment were observed on treated items.


Efficacy of single-agent decitabine in relapsed and refractory acute myeloid leukemia.
Improving therapy for relapsed/refractory AML remains a challenge. We performed a retrospective analysis of outcomes following decitabine treatment in 34 patients with relapsed/refractory AML (median age, 62; median Charlson comorbidity score, 6). Decitabine, 20 mg/m2 daily, was given in 5- (25%) or 10-day (75%) cycles. Overall response rate (OR) was 30% with 21% complete remission and 9% partial remission rate. Patients with therapy-related myeloid neoplasm (t-MN) and secondary AML had a significantly higher OR compared to those with de novo AML (70 vs. 30%; p = .02). Median overall survival of all patients was 8.5 months. Median survival in patients with t-MN or secondary AML was 12.4 months compared to 8 months in those with de novo AML (p = .20). Fifteen (44%) patients proceeded to hematopoietic stem cell transplant. These data support using 10-day treatment cycles of decitabine in patients with relapsed/refractory AML, particularly for those with secondary or therapy-related AML.


Therapeutic superiority of maprotiline versus doxepin in geriatric depression.
In a double-blind study, 49 geriatric patients suffering from primary major depression were treated with maprotiline or doxepin. Efficacy and safety were assessed by the Hamilton Depression Rating Scale and the Zung Self-Rating Depression and Anxiety scales, side effects profile, routine laboratory tests, and measurements of blood levels. Although marked improvement was obtained with both antidepressants, patients on maprotiline showed statistically greater improvement than those on doxepin. No significant differences were detected between the two drugs with respect to side effects. A significant positive correlation was obtained between dosage and blood levels of maprotiline and doxepin, but there was no correlation between blood levels and clinical response. Overall, results suggest that maprotiline may be superior to doxepin in the treatment of geriatric depression.


The NAC transcription factors NST1 and NST2 of Arabidopsis regulate secondary wall thickenings and are required for anther dehiscence.
In plants, secondary wall thickenings play important roles in various biological processes, although the factors regulating these processes remain to be characterized. We show that expression of chimeric repressors derived from NAC SECONDARY WALL THICKENING PROMOTING FACTOR1 (NST1) and NST2 in Arabidopsis thaliana resulted in an anther dehiscence defect due to loss of secondary wall thickening in anther endothecium. Plants with double, but not single, T-DNA-tagged lines for NST1 and NST2 had the same anther-indehiscent phenotype as transgenic plants that expressed the individual chimeric repressors, indicating that NST1 and NST2 are redundant in regulating secondary wall thickening in anther walls. The activity of the NST2 promoter was particularly strong in anther tissue, while that of the NST1 promoter was detected in various tissues in which lignified secondary walls develop. Ectopic expression of NST1 or NST2 induced ectopic thickening of secondary walls in various aboveground tissues. Epidermal cells with ectopic thickening of secondary walls had structural features similar to those of tracheary elements. However, among genes involved in the differentiation of tracheary elements, only those related to secondary wall synthesis were clearly upregulated. None of the genes involved in programmed cell death were similarly affected. Our results suggest NAC transcription factors as possible regulators of secondary wall thickening in various tissues.


Negative affect is unrelated to fluctuations in hormone levels across the menstrual cycle: Evidence from a multisite observational study across two successive cycles.
Female sex hormones may play a crucial role in the occurrence of cycle-related mood disorders. However, the literature is inconsistent and methodologically stringent observational studies on the relationship between sex hormones and negative affect are lacking. In this longitudinal multisite study from Hannover, Germany, and Zurich, Switzerland, we examined oestrogen, progesterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone serum levels in association with negative affect as measured with the Positive and Negative Affect Schedule (PANAS). Negative affect and hormone assays were collected at four consecutive time points comprising menstrual, pre-ovulatory, mid-luteal and premenstrual phase across two cycles (n=87 and n=67 for the first and second cycles). The Beck Depression Inventory (BDI) was assessed once prior to the first cycle and included as a secondary measure. Mean negative affect scores did not significantly fluctuate across both cycles and there was in particular no symptom increase premenstrually. No sex hormone consistently related to repeated measures of negative affect across two consecutive cycles. The BDI sum-score assessed at baseline was not related to hormone levels across the first cycle. This is the first multisite longitudinal study on the association between negative affect and sex hormone levels encompassing two consecutive menstrual cycles. Negative affect did not fluctuate across the cycle and there was no direct and uniform association between sex hormones and self-reported negative affect. These findings suggest that moderators such as personality traits and epigenetics should be considered in future research.


Influence of diabetes mellitus on inappropriate and appropriate implantable cardioverter-defibrillator therapy and mortality in the Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT) Trial.
The relationship between diabetes mellitus and risk of inappropriate or appropriate therapy in patients receiving an implantable cardioverter-defibrillator (ICD) and resynchronization therapy has not been investigated thoroughly. The effect of innovative ICD programming on therapy delivery in these patients is unknown. The Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT) randomized patients with a primary prophylactic ICD indication to 3 different types of ICD programming: conventional programming with a ventricular tachycardia zone of 170 to 199 bpm (arm A), high-rate cutoff with a ventricular tachycardia zone ≥200 bpm (arm B), or 60-second-delayed therapy (arm C). The end points of inappropriate therapy, appropriate therapy, and death were assessed among 485 patients with and 998 without diabetes mellitus. Innovative ICD programming reduced the risk of inappropriate therapy regardless of diabetes mellitus, although a trend toward a more pronounced effect of high-rate cutoff programming was seen in patients without diabetes mellitus (P for interaction=0.06). Diabetes mellitus was associated with a decreased risk of inappropriate therapy (hazard ratio, 0.54; 95% confidence interval, 0.36-0.80; P=0.002) and increased risk of appropriate therapy (hazard ratio, 1.58; 95% confidence interval, 1.17-2.14; P=0.003). In diabetic patients, there was significantly increased risk of death in those who had inappropriate therapy (hazard ratio, 4.17; 95% confidence interval, 1.52-11.40; P=0.005) and appropriate therapy (hazard ratio, 2.49; 95% confidence interval, 1.06-5.87; P=0.037) compared with those who did not. Innovative high-rate cutoff or delayed ICD programming was associated with a reduction in inappropriate therapy in patients with and without diabetes mellitus. Diabetes mellitus was associated with lower risk of inappropriate therapy but higher risk of appropriate therapy. Appropriate and inappropriate ICD therapy was associated with increased mortality in diabetic patients. URL: http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT00947310.


Physical and Physiological Factors Influence Behavioral Responses of Cochliomyia macellaria (Diptera: Calliphoridae) to Synthetic Attractants.
Volatile chemicals from waste artificial larval media as well as from bovine blood inoculated with bacteria isolated from screwworm-infested wounds attract gravid females of Cochliomyia hominivorax Coquerel and Cochliomyia macellaria (F.). Chemicals identified from volatiles are dimethyl disulfide, dimethyl trisulfide, phenol, p-cresol, and indole; a blend of these attracted females to oviposit. Present studies investigated the effectiveness of these compounds, either in a blend or individually as potential oviposition attractants. Tests were conducted to determine the effects of gender, ovarian age, and the color and type of substrates on attraction response and oviposition of C. macellaria adults. Results showed that substrates treated with dimethyl trisulfide (DMTS) alone or the five-compound blend alone attracted significantly more gravid females than other chemicals. Black substrates treated with DMTS attracted more gravid flies than did the yellow substrates. Yellow substrates treated with indole attracted more males and nongravid females. In oviposition tests, females deposited significantly more eggs on meat-based substrates than those without meat. These findings suggest that several factors have to be considered for developing an effective oviposition attractant that should include effectiveness of individual chemicals used, the ratio of the chemicals in a blend, and their concentrations. Also, an effective trap design will need to consider using suitable color which will selectively attract gravid females.


Black and white patients fare equally well when treated with postlumpectomy radiotherapy.
Some previous studies have demonstrated that black patients have inferior local-regional control and disease-free survival when treated with postlumpectomy radiotherapy. The intention of this study was to analyze the same outcomes with a larger series of black patients. A retrospective chart review was performed at an academic referral center, a community hospital, and an inner-city public hospital. A total of 270 patients that received postlumpectomy radiotherapy were reviewed. Of those, 102 were black, 162 white, and six nonblack, nonwhite. The black patients were statistically significantly more likely to present with higher-stage disease (Stage II: 43.1% vs. 32.1%), positive lymph nodes (29.4% vs. 14.8%), higher-grade disease (Grade III: 35.3% vs. 24.1%), and age < 45. The actuarial local control at five years in the black patients was 95.5% and in the white patients was 94.8%. The actuarial five-year disease-free survival in the black patients was 90.3% and in the white patients was 91.7%. There was no statistically significant difference in either local control or disease free-survival in the black and white patients when matched by stage. At five years, the local control and disease-free survival for black patients are equally as good as white patients.


[Resistance to antimicrobiotics and mutation of PBPs in Streptococcus pneumoniae isolated from Kinki region of Japan].
We studied the susceptibility to penicillin G (PCG) and other antimicrobiotics in 235 clinical isolates of Streptococcus pneumoniae. Samples were collected between April 1 and June 30, 2000 from nine medical institutions of the Kinki Region of Japan. We classified the minimum inhibitory concentration (MIC) of PCG according to the National Committee for Clinical Laboratory Standards (NCCLS) criteria. The overall rate of all types of S. pneumoniae resistance was 53.2% (penicillin-susceptible S. pneumoniae (PSSP): 46.8%, penicillin-intermediate S. pneumoniae (PISP): 42.6%, penicillin-resistant S. pneumoniae (PRSP): 10.6%). In other antimicrobiotics, the resistance (R)/intermediate susceptibility (I) rates (R/I%) were as follows: ceftriaxone, 28.9%; cefotaxime, 7.7%; imipenem, 8.9%; meropenem, 9.8%; clarithromycin, 82.6%; clindamycin, 42.1%; levofloxacin, 0.4%; vancomycin, 0%. We used the polymerase chain reaction to study the mutations of the penicillin-binding proteins pbp1 a, pbp2b, and pbp2x in 140 strains of S. pneumoniae in the MIC for PCG was < 0.5 microgram/ml. Among the 109 strains of PSSP, 32 (29.4%) had no mutation and 77 (70.6%) showed mutation of more than one of the pbp mutations. Among the 31 strains of PISP, only 1 strain (3.2%) was not mutated. Since 70.6% of the strains classified as PSSP had pbp mutations, S. pneumoniae clearly can acquire resistance to anti-microbiotics. In the future, a comprehensive surveillance of S. pneumoniae is necessary.


Adjunctive aripiprazole in bipolar I depression.
Aripiprazole has demonstrated efficacy in treatment of bipolar mania, as well as in the maintenance treatment of bipolar disorder. There has been only one report supporting a role for this agent in the depressed phase of the illness. To evaluate the effectiveness of adjunctive aripiprazole in bipolar I depressed patients who are nonresponders to standard therapy. Chart records were reviewed for all patients with bipolar I depression, diagnosed by Diagnostic and Statistical Manual of Mental Disorders, 4th revision, criteria between June 2004 and January 2006 from the Long Beach Veterans Affairs Mood Disorders Clinic. Included subjects had experienced moderate to marked depressive symptoms (Clinical Global Impression-Bipolar Depression > or =4) despite at least 2 months of treatment with adequate doses of at least one mood stabilizer. In addition, all subjects had been treated subsequently with aripiprazole 15-30 mg/day added to the existing regimen. Detailed chart notes were used to retrospectively rate symptoms. The presence or absence of each symptom was recorded before and after aripiprazole augmentation. Based on these data, Clinical Global Impression bipolar severity (CGI-BP-S) ratings and CGI-BP improvement scores for bipolar I depression were assigned. Ten subjects met study criteria. Adjunctive aripiprazole given for 21-110 days resulted in significant improvements in CGI-BP-S depression ratings. Seven of 10 patients were assigned CGI-BP improvement ratings of much or very much improved. Adverse events were mild and included akathisia, nausea, and insomnia. Dose adjustments of aripiprazole or the addition of drugs to treat adverse effects excluded subjects from further data collection. No patient stopped aripiprazole due to adverse effects. This study adds to a previous report indicating beneficial effects of adjunctive aripiprazole in treatment of bipolar I depression. Double-blind, placebo-controlled investigations are needed to confirm these findings.


Temperature and time variations during osteotomies performed with different piezosurgical devices: an in vitro study.
The aim of this experimental in vitro study was to evaluate the effects of the piezoelectric device in temperature and time variations in standardized osteotomies performed with similar tip inserts in bovine bone blocks. Two different piezosurgical devices were used the OE-F15(®) (Osada Inc., Los Angeles, California, USA) and the Surgybone(®) (Silfradent Inc., Sofia, Forli Cesena, Italy). Serrated inserts with similar geometry were coupled with each device (ST94 insert/test A and P0700 insert/test B). Osteotomies 10 mm long and 3 mm deep were performed in bone blocks resembling type II (dense) and type IV (soft) bone densities with and without irrigation. Thermal changes and time variations were recorded. The effects of bone density, irrigation, and device on temperature changes and time necessary to accomplish the osteotomies were analyzed. Thermal analysis showed significant higher temperatures during piezosurgery osteotomies in hard bone without irrigation (P < 0.05). The type of piezosurgical device did not influence thermal variations (P > 0.05). Time analysis showed that the mean time values necessary to perform osteotomies were shorter in soft bone than in dense bone (P < 0.05). Within the limitations of this in vitro study, it may be concluded that the temperature increases more in piezosurgery osteotomies in dense bone without irrigation; the time to perform the osteotomy with piezosurgery is shorter in soft bone compared to hard bone; and the piezosurgical device have a minimal influence in the temperature and time variations when a similar tip design is used during piezosurgery osteotomies.


Delivery by cationic gelatin nanoparticles strongly increases the immunostimulatory effects of CpG oligonucleotides.
Cationized gelatin nanoparticles (GNPs) were used as carrier to improve delivery of immunostimulatory CpG oligonucleotides (CpG ODN) both in vitro and in vivo. Uptake of CpG ODN-loaded cationized gelatin nanoparticles (CpG-GNPs) into murine myeloid dendritic cells (DCs) and their respective immunostimulatory activity was monitored. In vivo, induction of cytokine secretion by CpG-GNPs was measured. For experiments on primary human cells, prototypes of the three CpG ODN classes were adsorbed onto GNPs. Uptake and induction of proinflammatory cytokines were assessed in human plasmacytoid DCs and B cells, the only existing human target cells for CpG ODN. In the murine system, gelatin nanoparticle formulations enhanced the uptake and immunostimulatory activity of CpG ODN both in vitro and in vivo. Furthermore, delivery by cationized gelatin nanoparticles of CpG ODN of the classes B and C to primary human plasmacytoid DCs increased production of IFN-alpha, a key cytokine in the driving of both the innate and adaptive immune responses. GNPs can be used as a biodegradable and well tolerated carrier to deliver CpG ODN to their target cells and strongly increase activation of the immune system. This concept may be applied as novel adjuvant for antiviral and antitumoral vaccines.


High HIV seroconversion rate in hepatitis C virus-infected drug users followed in a harm reduction unit: a lost opportunity for preexposure prophylaxis.
Current harm reduction strategies will probably remain insufficient to eliminate HIV transmission among drug users. We aimed to estimate the HIV seroconversion rate among drug users followed at a harm reduction unit (HRU) to evaluate the potential use of preexposure prophylaxis as a prevention tool. A cohort of drug users has been followed at an HRU in Madrid between 2013 and 2016. Individuals who were HIV negative at baseline and who had at least one retest for HIV infection were eligible. Kaplan-Meier methods were employed to estimate the incidence density. A total of 954 drug users had at least an HIV test. At baseline, 260 were HIV negative and had at least one follow-up HIV test. After 330.89 person-years of risk for HIV infection, 10 (3.8%) seroconverted. Overall incidence density of HIV seroconversion was 3.02 [95% confidence interval (CI); 1.4-5.5] per 100 person-years, with differences according to hepatitis C virus (HCV) serostatus: 1.17 (95% CI; 0.1-4.2) per 100 person-years in negative HCV individuals and 4.98 (95% CI; 2.1-9.8) per 100 person-years in positive HCV individuals. In the multivariable analysis, infection with HCV remained independently associated with time to HIV seroconversion (adjusted hazard ratio = 6.43; 95% CI; 1.1-36.5, P = 0.035). Despite efforts in HIV prevention in a HRU, a high incidence of HIV was found among active drug users. Positive HCV status is a strong predictor of HIV seroconversion. In this context, preexposure prophylaxis implementation should be considered as an additional tool for HIV prevention in this population.


High-Throughput Analysis of Plasma Hybrid Markers for Early Detection of Cancers.
Biomarkers for the early detection of cancer in the general population have to perform with high sensitivity and specificity in order to prevent the costs associated with over-diagnosis. There are only a few current tissue or blood markers that are recommended for generalized cancer screening. Despite the recognition that combinations of multiple biomarkers will likely improve their utility, biomarker panels are usually limited to a single class of molecules. Tissues and body fluids including plasma and serum contain not only proteins, DNA and microRNAs that are differentially expressed in cancers but further cancer specific information might be gleaned by comparing different classes of biomolecules. For example, the level of a certain microRNA might be related to the level of a particular protein in a cancer specific manner. Proteins might have cancer-specific post-translational modifications (e.g., phosphorylation or glycosylation) or lead to the generation of autoantibodies. Most currently approved biomarkers are glycoproteins. Autoantibodies can be produced as a host's early surveillance response to cancer-specific proteins in pre-symptomatic and pre-diagnostic stages of cancer. Thus, measurement of the level of a protein, the level of its glycosylation or phosphorylation and whether autoantibodies are produced to it can yield multi-dimensional information on each protein. We consider specific proteins that show consistent cancer-specific changes in two or three of these measurements to be "hybrid markers". We hypothesize these markers will suffer less variation between different individuals since one component can act to "standardize" the other measurement. As a proof of principle, a 180 plasma sample set consisting of 120 cases (60 colon cancers and 60 adenomas) and 60 controls were analyzed using our high-density antibody array for changes in their protein, IgG-complex and sialyl-Lewis A (SLeA) modified proteins. At p < 0.05, expression changes in 1,070 proteins, 49 IgG-complexes (11 present in the protein list) and 488 Lewis X-modified proteins (57 on the protein list) were observed. The biomarkers significant on both lists are potential hybrid markers. Thus, plasma hybrid markers have the potential to create a new class of early detection markers of cancers.


The right start.
Susquehanna Health System, a three-hospital healthcare system based in Williamsport, Pa., reengineered its business processes and introduced new technology to capture patient information more accurately at the time of service. Set to go live in July, the new system already is reducing staff training needs and promises to significantly ease registration burdens.


Successful treatment of thyrotoxic crisis with plasma exchange.
A 36-yr-old woman with thyroid storm was successfully treated with plasma exchange. After the first plasma exchange, free serum thyroxine (T4) was decreased and serum thyroxine-binding globulin (TBG) was significantly increased. The decrease in the patient's free T4 level after plasma exchange can perhaps be attributed to T4's increased binding capacity. Plasma exchange may be an effective therapy for thyrotoxic crisis and should be performed immediately if conventional therapy fails to improve the patient's condition.


Development of the primary bacterial microfouling layer on antifouling and fouling release coatings in temperate and tropical environments in Eastern Australia.
The role played by bacteria during the pioneering stages of colonisation on marine coatings was investigated over three distinct seasons in both tropical and temperate environments. Novel methods were developed to facilitate the study of the adhered bacterial population on the test coatings in their native, hydrated state. The approach eliminated destructive sample preparation techniques, including sample dehydration and/or removal from the substratum surface prior to analysis. Bacterial colonisation during initial biofilm formation was evaluated on two antifouling paints, Intersmooth 360 and Super Yacht 800, and a fouling release coating, Intersleek 700. Bacterial colonisation was quantified on all three coating surfaces. Intersleek 700 displayed the quickest colonisation by bacteria, resulting in major modification of the substratum surface within 2-4 days following immersion in the ocean. Whilst fouling accumulated more quickly on Intersleek 700, by 16 days all three coatings were fouled significantly. Bacterial fouling was correlated to both location and season, with fouling occurring at a more rapid rate at the Cairns location, as well as during the summer months, when higher water temperatures were recorded. Successful colonisation of all coatings by bacteria soon after immersion modifies the characteristics of the surfaces at the hull/water interface, and subsequent settlement by higher biofouling organisms must be moderated by these modified surfaces.


Gastric bariatric operation in insulin-treated adults.
Gastric bariatric operation has been advocated to ameliorate adult-onset diabetes mellitus in the morbidly obese patient. However, there are few data to support this. In this clinical study we report the cases of 23 insulin-treated, morbidly obese, adult-onset diabetes (type II) patients who underwent gastric bariatric operations for weight reduction. Preoperative insulin requirements ranged from 10 to 230 U/day (mean 74 U/day). After operation, 14 patients discontinued insulin, and seven patients decreased their insulin requirement by 72% (100 to 28 U/day). Two patients were lost to follow-up. Six patients were admitted to the Clinical Research Unit before and after operation to evaluate the effects of surgically induced weight loss on fasting blood glucose levels, hemoglobin A1C insulin resistance, and glucose tolerance. Weight loss at the time of postoperative studies ranged between 22.5 and 49.1 kg (mean 30.6 kg). Fasting blood glucose levels decreased 48% (mean 321 mg/dl before operation to 166 mg/dl after operation). Hemoglobin A1C levels improved from a mean of 11.8% to 7.9%. Insulin resistance assessed in four patients by measurement of glucose clearance during insulin and glucose infusion improved from a mean of 77 ml/min before operation to 228 ml/min after operation. Glucose tolerance was quantitated by determination of glucose disappearance during intravenous glucose tolerance test. The mean glucose disappearance improved from 0.176% to 0.385%/min following operation. This study provides clinical and laboratory evidence indicating significant improvement of insulin-treated diabetes mellitus in morbidly obese patients who have lost weight following gastric bariatric operation.


Copper-catalyzed aerobic oxidative coupling of aromatic alcohols and acetonitrile to β-ketonitriles.
A practical, convenient, and cheap copper-catalyzed aerobic oxidative coupling of aromatic alcohols and acetonitrile to β-ketonitriles has been developed. The green C-C bond formation involving the loss of two hydrogen atoms from the corresponding two carbons, respectively, unlocks opportunities for markedly different synthetic strategies.


[Vegetable oil-induced acute respiratory distress syndrome (ARDS) in near drowning: evaluation based on extravascular lung water index].
Lipoid pneumonia usually presents after chronic recurrent ingestion of oily substances or accidental aspiration during "fire-eating" demonstrations. Massive exposure by near drowning extremely rare and potentially fatal. We present here a case of survival after total immersion in oil in her workplace. A 66-year-old woman who nearly drowned in a vat of vegetable oil was admitted as an emergency case with severe hypoxia after rescue. Chest computed tomography (CT) findings showed bilateral ground-glass opacity, consolidation, and the case fulfilled the criteria for acute respiratory distress syndrome (ARDS). Bronchoscopy and bronchoalveolar lavage performed on admission indicated oil droplets and marked neutrophilia (67%), which made us diagnose ARDS induced by lipoid pneumonia. We commenced treatment with pulsed steroids and strictly managed fluid balance under mechanical ventilation. Despite immediate improvement in oxygenation, the value of extravascular lung water index (EVLWI) measured by the PiCCO system consistently remained over 30 ml/Kg through her clinical course. We concluded that lipoid pneumonia is characterized by prolonged elevatation of pulmonary vascular permeability.


Claudin-8d is a cortisol-responsive barrier protein in the gill epithelium of trout.
The influence of claudin (Cldn) 8 tight junction (TJ) proteins on cortisol-mediated alterations in gill epithelium permeability was examined using a primary cultured trout gill epithelium model. Genes encoding three Cldn-8 proteins (cldn-8b, -8c and -8d) have been identified in trout and all are expressed in the model gill epithelium. Cortisol treatment 'tightened' the gill epithelium, as indicated by increased transepithelial resistance (TER) and reduced paracellular [3H]polyethylene glycol (MW 400 Da; PEG-400) flux. This occurred in association with elevated cldn-8d mRNA abundance, but no alterations in cldn-8b and -8c mRNA abundance were observed. Transcriptional knockdown (KD) of cldn-8d inhibited a cortisol-induced increase in Cldn-8d abundance and reduced the 'epithelium tightening' effect of cortisol in association with increased paracellular PEG-400 flux. Under simulated in vivo conditions (i.e. apical freshwater), cldn-8d KD hindered a cortisol-mediated reduction in basolateral to apical Na+ and Cl- flux (i.e. reduced the ability of cortisol to mitigate ion loss). However, cldn-8d KD did not abolish the tightening effect of cortisol on the gill epithelium. This is likely due, in part, to the effect of cortisol on genes encoding other TJ proteins, which in some cases appeared to exhibit a compensatory response. Data support the idea that Cldn-8d is a barrier protein of the gill epithelium TJ that contributes significantly to corticosteroid-mediated alterations in gill epithelium permeability.


Genomic selection in a pig population including information from slaughtered full sibs of boars within a sib-testing program.
Genomic selection is becoming a common practise in dairy cattle, but only few works have studied its introduction in pig selection programs. Results described for this species are highly dependent on the considered traits and the specific population structure. This paper aims to simulate the impact of genomic selection in a pig population with a training cohort of performance-tested and slaughtered full sibs. This population is selected for performance, carcass and meat quality traits by full-sib testing of boars. Data were simulated using a forward-in-time simulation process that modeled around 60K single nucleotide polymorphisms and several quantitative trait loci distributed across the 18 porcine autosomes. Data were edited to obtain, for each cycle, 200 sires mated with 800 dams to produce 800 litters of 4 piglets each, two males and two females (needed for the sib test), for a total of 3200 newborns. At each cycle, a subset of 200 litters were sib tested, and 60 boars and 160 sows were selected to replace the same number of culled male and female parents. Simulated selection of boars based on performance test data of their full sibs (one castrated brother and two sisters per boar in 200 litters) lasted for 15 cycles. Genotyping and phenotyping of the three tested sibs (training population) and genotyping of the candidate boars (prediction population) were assumed. Breeding values were calculated for traits with two heritability levels (h 2=0.40, carcass traits, and h 2=0.10, meat quality parameters) on simulated pedigrees, phenotypes and genotypes. Genomic breeding values, estimated by various models (GBLUP from raw phenotype or using breeding values and single-step models), were compared with the classical BLUP Animal Model predictions in terms of predictive ability. Results obtained for traits with moderate heritability (h 2=0.40), similar to the heritability of traits commonly measured within a sib-testing program, did not show any benefit from the introduction of genomic selection. None of the considered genomic models provided improvements in prediction ability of pigs with no recorded phenotype. However, a few advantages were found for traits with low heritability (h 2=0.10). These heritability levels are characteristic for meat quality traits recorded after slaughtering or for reproduction or health traits, typically recorded on field and not in performance stations. Other scenarios of data recording and genotyping should be evaluated before considering the implementation of genomic selection in a pig-selection scheme based on sib testing of boars.


Exploration of alginates as potential stabilizers of nanosuspension.
The objective of this study was to explore the feasibility of using alginate as a potential stabilizer of nanosuspension and elaborate the corresponding stabilization mechanism. Using lovastatin as a Biopharmaceutics Classification System (BCS) II drug model, alginate-stabilized nanosuspension was fabricated by the high-pressure homogenization method. The particle size, zeta potential, short-term stability, and dissolution behavior of the nanosuspension were characterized. Thereafter, the surface morphology, crystallinity, redispersability, and stability of the spray-dried nanosuspension were investigated. The spray-dried powder was further compressed into tablets via direct compression, and stressing test was carried out to investigate the stability of nanocrystal loaded tablets. It was demonstrated that alginate could stabilize nanocrystals by providing both electrostatic and steric stabilization, and the effective concentration was much lower than that of the commonly used stabilizers. Good redispersability was achieved after spray drying of the nanosuspension, and the existing state of lovastatin was not changed as indicated by X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) studies. The stress test indicated that nanocrystal-loaded tablets possessed a favorable stability. In conclusion, alginate could be used as a potential stabilizer of nanosuspension with preferable stabilizing ability at a very low concentration either in liquid or in solid state.


Routine urinalysis in a male working population: effects of some personal and lifestyle factors.
The most frequently positive urinalysis findings in a population of white working men were leukocytes (78.7%), erythrocytes (37.3%) and protein (25.4%). There was a significant correlation among the variables: cells were associated with protein, protein was associated with casts, erythrocytes were associated with granular casts and oxalate crystals. Protein and granular casts were significantly associated with serum creatinine. The prevalence of blood cells varied with age, showing a bimodal distribution. Oxalate crystals were significantly more common in subjects with a history of urinary tract infection; triple phosphate crystals were associated with a history of urinary calculi. Protein and erythrocytes were significantly more frequent in smokers. Leukocytes were significantly more frequent in drinkers. We conclude that there are important factors that must be taken into account in the interpretation of urinalysis findings.


Computerized tracking for newborn screening and follow-up: a review.
In the third decade of newborn screening for phenylketonuria (PKU) and other disorders computers are being used increasingly for both the laboratory and the follow-up aspects of screening programs. In 1984 slightly less than 40% of the state programs had automated follow-up. Lack of funding is probably the major inhibitor of more widespread use of computers in tracking newborns through the newborn screening process. It is suggested that federal funds be made available to ensure wider distribution of currently used tracking systems and development of methods for tracking newborns from birth through follow-up.


Sulindac induces apoptosis, inhibits proliferation and activates caspase-3 in Hep G2 cells.
It has recently been reported that sulindac has an apoptotic effect on KYN-2 cells, an undifferentiated hepatoma cell line. The present work investigates whether sulindac also has an apoptotic effect on well-differentiated hepatoma cells and what its potential mechanism might be. Hep G2 cells were treated with sulindac at different concentrations. Apoptosis rate, cell proliferation and 3H-thymidine incorporation were measured. The activities of caspase-3, acid and neutral sphingomyelinase and the changes of sphingomyelin content were also assayed. Sulindac dose-dependently induced apoptosis in Hep G2 cells; both sulindac sulfone and sulfide had similar effects. The apoptosis was accompanied by an increase of caspase-3 activity and a decrease of cell proliferation and 3H-thymidine incorporation. No significant change could be observed for the activity of sphingomyelinase and sphingomyelin content. Sulindac induces apoptosis and inhibits proliferation in Hep G2 cells. The effect may be mediated by a pathway related to caspase-3 activation but independent of sphingomyelin metabolism


A standardized plane for biparietal diameter measurement.
Biparietal diameter measurement is the most widely accepted means of determining gestational age. However, a standard anatomic plane for performing this measurement has not been established. Three hundred forty-four measurements on 256 patients who gave birth to normal infants were obtained and compared at various cranial levels based on brain anatomy. The results document that use of a standardized plane increases measurement reliability but does not significantly alter variability. We postulate that variability is based predominantly on biologic variation in fetal growth rates rather than on technical errors.


Rapid identification of swarming Proteus using the PathoTec ornithine decarboxylase test strip.
The PathoTec ornithine decarboxylase test strip was evaluated for use in identification of swarming Proteus. All 181 strains tested were accurately identified within 4 h.


A review of surgical techniques for radical prostatectomy.
Since the early 20th century, radical prostatectomy has been used in the treatment of prostate cancer. However, before the widespread acceptance of prostate-specific antigen screening, the majority of cancers were clinically advanced and not amenable to cure, so relatively few men were candidates for this procedure. Modern advances have contributed dramatically to the reduction of complications and morbidity associated with radical prostatectomy. As a result, the procedure has become the most common treatment selected by men with localized prostate cancer. This article reviews several issues regarding radical prostatectomy, including surgical techniques, cancer control, intraoperative localization of the cavernous nerves, patient selection, and laparoscopic versus robotic approaches.


Direct application of basic fibroblast growth factor improves tympanic membrane perforation healing.
Topical application of basic fibroblast growth factor (b-FGF) on tympanic membrane (TM) perforations was studied in guinea pigs. One-millimeter simple round TM perforations or 2-mm TM perforations with medially flapped borders were performed. Either b-FGF or placebo was instilled in each ear on the day of surgery and daily thereafter. Treatment was applied either directly to the perforation or to a Gelfoam pledget over the defect. When no scaffolding material was interposed, b-FGF induced a faster healing response characterized by a hyperplastic but linear subepidermal connective tissue reaction compared to the control. When Gelfoam was interposed as a scaffold, a voluminous scar protruding into the middle ear cavity and involving the ossicles was observed in both b-FGF and control animals. Gelfoam-induced scars did not decrease after long-term observation, therefore discouraging its use.


A Multidimensional View of Charge Transfer Excitons at Organic Donor-Acceptor Interfaces.
How tightly bound charge transfer (CT) excitons dissociate at organic donor-acceptor interfaces has been a long-standing question in the organic photovoltaics community. Recently, it has been proposed that exciton delocalization reduces the exciton binding energy and promotes exciton dissociation. In order to understand this mechanism, it is critical to resolve the evolution of the exciton's binding energy and coherent size with femtosecond time resolution. However, because the coherent size is just a few nanometers, it presents a major experimental challenge to capture the CT process simultaneously in the energy, spatial, and temporal domains. In this work, the challenge is overcome by using time-resolved photoemission spectroscopy. The spatial size and electronic energy of a manifold of CT states are resolved at the zinc phthalocyanine (ZnPc)-fullerene (C60) donor-acceptor interface. It is found that CT at the interface first populates delocalized CT excitons with a coherent size of 4 nm. Then, this delocalized CT exciton relaxes in energy to produce CT states with delocalization sizes in the range of 1-3 nm. While the CT process from ZnPc to C60 occurs in about 150 fs after photoexcitation, the localization and energy relaxation occur in 2 ps. The multidimensional view on how CT excitons evolve in time, space, and energy provides key information to understand the exciton dissociation mechanism and to design nanostructures for effective charge separation.