Health care coverage for children who are on and off welfare.
Access to adequate health insurance is a key concern of families with children at all income levels. Since 1965, mothers and children on welfare have had health care coverage through the Medicaid program, which has provided a health care safety net for welfare recipients. Although most Americans are insured through their employers, families who leave welfare for employment often find themselves in jobs that do not offer health care coverage, adding to the ranks of the uninsured. This article examines the extent to which poor children and their mothers have private insurance, Medicaid, or no health insurance at all. It documents how recent expansions of Medicaid eligibility to low-income children who do not receive welfare have improved the insurance status of children, though these changes have not helped the mothers who leave welfare for work. Citing evidence that health insurance options influence the welfare and employment decisions of women whose families face health problems, the article suggests that implementing welfare reform at a time when rates of private insurance coverage are declining will be challenging and may expose some families to health risks.


The Effect of Moving Window on Acoustic Analysis.
To investigate the effects of the moving window method on acoustic measures and discrimination ability between normal and disordered voices. Fifty-three normal voices and 50 disordered voices were recruited. Three selection methods, the moving window method, the mid-vowel method, and the whole vowel method, were applied to each raw audio signal to determine the most stable segment of each signal. Acoustic parameters such as percent jitter, percent shimmer, signal-to-noise ratio (SNR), cepstral peak prominence (CPP), and correlation dimension (D2) were calculated. The Wilcoxon test was used to compare the stability of these segments across different methods. An artificial neural network was used for estimating how well disordered voices were discriminated from normal ones. Segments selected using the moving window method were more stable than those selected using the other two methods, meaning lower perturbation and nonlinear dynamic measurements as well as higher SNR and CPP values. The discrimination accuracy rate for the moving window method was 91.90 ± 8.73%, whereas the mid-vowel method and the whole vowel method were 72.34 ± 12.94% and 70.34 ± 5.24%, respectively. The moving window method is capable of providing a more stable audio segment and can discriminate disordered voices from normal ones more effectively.


Interleukin-18 gene promoter polymorphisms and celiac disease in Italian patients.
Celiac disease (CD) is the most common food-sensitive enteropathy in genetically susceptible individuals. The major genetic risk factors known are specific human leukocyte antigen (HLA)-DQ haplotypes, but other genetic factors are supposed to be involved. Interleukin-18 (IL-18) is a pro-inflammatory cytokine that has an important role in the immune defense and it has the potential to influence inflammatory disorders. IL-18 is able to promote Th1 cell development and it is expressed in the mucosa of the small intestine in celiac patients. Given the IL-18 biological role, and since a few studies have previously suggested its involvement in CD, in order to investigate the role of IL18 gene in the susceptibility to CD we have performed a case-control study, analyzing two IL18 gene promoter polymorphisms, previously reported to impair the transcriptional activity of the gene, (-137G > C and -607C > A, rs187238 and rs1946518 respectively). A total of 556 CD Italian patients and 582 controls, further stratified for HLA class II (DQ) CD risk haplotypes were enrolled. The -607A > C A allele and A/A genotype, as well as the combination of this allele with the -137G allele in the AG haplotype, were associated with an increased risk towards CD development, in particular in HLA-DQ2.2 patients. Although the association was very moderate, our results indicate the possible involvement of IL18 gene in the susceptibility to CD, and for this reason we do think it should deserve further investigation.


An update on the role of medical treatment including antioxidant therapy in varicocele.
Varicocele-associated male infertility has classically been managed using surgery or assisted reproductive techniques. With increasing evidence of oxidative stress as a pathophysiological factor in varicocele-associated infertility, medical therapy especially antioxidants might become a treatment option with lower risks. We reviewed the existing literature on the role of various medical agents in the management of male infertility attributed to varicoceles. Medical therapy is typically evaluated in three different situations such as (a) comparison of two drugs or one drug with placebo, (b) comparison of drugs versus surgery, and (c) comparison of drugs as adjuvant therapy with surgery versus drug therapy alone. Due to heterogeneity of data and lack of well-conducted studies, there is insufficient data to recommend routine use of medical therapy for men with varicocele-associated infertility and surgery remains the treatment of choice. Pregnancy and live birth rates are usually not reported in most studies and mere improvement in sperm parameters or antioxidant capacity is insufficient to support its routine use. Antioxidant therapy is a potential option due to its theoretical benefit, data from preclinical studies, and lack of major side effects. Adjuvant therapy with antioxidants after surgical repair of varicocele may improve the outcome and is a potential area for further research.


Rational Combination of Immunotherapies with Clinical Efficacy in Mice with Advanced Cancer.
In the context of cancer, naïve T cells are insufficiently primed and become progressively dysfunctional. Boosting antitumor responses by blocking PD-1 or CTLA-4 results in durable clinical responses only in a limited proportion of cancer patients, suggesting that other pathways must be targeted to improve clinical efficacy. Our preclinical study in TRAMP mice comparing 14 different immune interventions identified anti-CD40 + IL2/anti-IL2 complexes + IL12Fc as a uniquely efficacious treatment that prevents tolerance induction, promotes priming of sustained, protective tumor-specific CD8(+) T cells, and cures late-stage cancer when given together with adoptively transferred tumor-specific T cells. We propose that improving signals 2 (costimulation) and 3 (cytokines) together with fresh tumor-specific, rather than boosting of dysfunctional preexisting memory, T cells represents a potent therapy for advanced cancer.


Three Years After Black Saturday: Long-Term Psychosocial Adjustment of Burns Patients as a Result of a Major Bushfire.
Despite increasing evidence that burn injuries can result in multiple psychological sequelae, little is known about the long-term psychosocial adjustment to burns sustained in a major bushfire. The aim of the present study was to assess long-term psychological distress and health-related quality of life in Australian burns patients as a result of the 2009 Black Saturday bushfires. Eight male and five female burns patients with a mean age of 53.92 (SD = 11.82) years who received treatment at a statewide burns service participated in the study. A battery of standardized questionnaires was administered to assess general psychological distress, burns-specific and generic health-related quality of life, alcohol use, and specific psychological symptoms of posttraumatic stress disorder, depression, and anxiety. The results revealed that more than 3 years after Black Saturday 33% of the burns patients still suffered "high" to "very high" levels of general distress, whereas 58% fulfilled partial or full criteria for posttraumatic stress disorder. Furthermore, participants still experienced significantly impaired physical health functioning as compared to their preinjury status including limitations in work-based activities, increased bodily pain, and lower vitality overall. The trajectory of distress varied for participants. Some individuals experienced little distress overall, whereas others displayed a decline in their stress levels over time. Notwithstanding, some patients maintained high levels of distress throughout or experienced an increase in distress at a later stage of recovery. The results point to the importance of psychosocial screening to identify distress early. Follow-up assessments are crucial to diagnose individuals with chronic or late onset of distress.


Changing effect of the numerator-denominator bias in unlinked data on mortality differentials by education: evidence from Estonia, 2000-2015.
This study highlights changing disagreement between census and death record information in the reporting of the education of the deceased and shows how these reporting differences influence a range of mortality inequality estimates. This study uses a census-linked mortality data set for Estonia for the periods 2000-2003 and 2012-2015. The information on the education of the deceased was drawn from both the censuses and death records. Range-type, Gini-type and regression-based measures were applied to measure absolute and relative mortality inequality according to the two types of data on the education of the deceased. The study found a small effect of the numerator-denominator bias on unlinked mortality estimates for the period 2000-2003. The effect of this bias became sizeable in the period 2012-2015: in high education group, mortality was overestimated by 23-28%, whereas the middle education group showed notable underestimation of mortality. The same effect was small for the lowest education group. These biases led to substantial distortions in range-type inequality measures, whereas unlinked and linked Gini-type measures showed somewhat closer agreement. The changing distortions in the unlinked estimates reported in this study warn that this type of evidence cannot be readily used for monitoring changes in mortality inequalities.


Aha1 binds to the middle domain of Hsp90, contributes to client protein activation, and stimulates the ATPase activity of the molecular chaperone.
The ATP-dependent molecular chaperone Hsp90 is an essential and abundant stress protein in the eukaryotic cytosol that cooperates with a cohort of cofactors/cochaperones to fulfill its cellular tasks. We have identified Aha1 (activator of Hsp90 ATPase) and its relative Hch1 (high copy Hsp90 suppressor) as binding partners of Hsp90 in Saccharomyces cerevisiae. By using genetic and biochemical approaches, the middle domain of Hsp90 (amino acids 272-617) was found to mediate the interaction with Aha1 and Hch1. Data base searches revealed that homologues of Aha1 are conserved from yeast to man, whereas Hch1 was found to be restricted to lower eukaryotes like S. cerevisiae and Candida albicans. In experiments with purified proteins, Aha1 but not Hch1 stimulated the intrinsic ATPase activity of Hsp90 5-fold. To establish their cellular role further, we deleted the genes encoding Aha1 and Hch1 in S. cerevisiae. In vivo experiments demonstrated that Aha1 and Hch1 contributed to efficient activation of the heterologous Hsp90 client protein v-Src. Moreover, Aha1 and Hch1 became crucial for cell viability under non-optimal growth conditions when Hsp90 levels are limiting. Thus, our results identify a novel type of cofactor involved in the regulation of the molecular chaperone Hsp90.


[Factors associated with necrotizing enterocolitis].
To evaluate the features of clinical presentation of neonatal necrotizing enterocolitis and its associated factors. Retrospective study of the cases of neonatal necrotizing enterocolitis (n = 56) diagnosed at Neonatal Intensive Care Unit Lagoa (NICU), between December 1986 and July 1992. Diagnosis and stages of the disease followed the modified Bell's criteria. Diagnosis and follow-up of all cases were evaluated. The cases of enterocolitis - degrees II and III (n = 44) - were subsequently selected and compared to a case-control group (n = 44), selected according to birthweight (+/- 250 g) and hospitalization period (+/- 2 weeks). The statistically significant analysis was considered as p < 0.05. Out of 2,447 newborns admitted to the NICU, 56 (2.3%) presented enterocolitis. Mean weight was 1908.5 g; mean gestational age was 35 weeks and 1 day; mean period for diagnosis was 10.7 days; 51 (91.1%) patients were fed before diagnosis; 18 (32.1%) needed urgent surgery; nine (16.9%) hemocultures were positive; 10 (17.8%) patients died. Four clinical standards were observed: fulminant, acute with pneumatosis, insidious and suspect. Comparatively to the case-control group, three factors were significantly associated with enterocolitis: apnea (p = 0.045), rapid increase of food intake (< 20 ml/kg/day) - (p = 0.048) and presence of infectious agent (p = 0.000). Significant factors associated with enterocolitis were occurrence of apnea, rapid increase of food intake and identification of the infectious agent.


Genomic dissection of maternal, additive and non-additive genetic effects for growth and carcass traits in Nile tilapia.
The availability of both pedigree and genomic sources of information for animal breeding and genetics has created new challenges in understanding how they can be best used and interpreted. This study estimated genetic variance components based on genomic information and compared these to the variance components estimated from pedigree alone in a population generated to estimate non-additive genetic variance. Furthermore, the study examined the impact of the assumptions of Hardy-Weinberg equilibrium (HWE) on estimates of genetic variance components. For the first time, the magnitude of inbreeding depression for important commercial traits in Nile tilapia was estimated by using genomic data. The study estimated the non-additive genetic variance in a Nile tilapia population of full-sib families and, when present, it was almost entirely represented by additive-by-additive epistatic variance, although in pedigree studies this non-additive variance is commonly assumed to arise from dominance. For body depth (BD) and body weight at harvest (BWH), the proportion of additive-by-additive epistatic to phenotypic variance was estimated to be 0.15 and 0.17 using genomic data (P < 0.05). In addition, with genomic data, the maternal variance (P < 0.05) for BD, BWH, body length (BL) and fillet weight (FW) explained approximately 10% of the phenotypic variances, which was comparable to pedigree-based estimates. The study also showed the detrimental effects of inbreeding on commercial traits of tilapia, which was estimated to reduce trait values by 1.1, 0.9, 0.4 and 0.3% per 1% increase in the individual homozygosity for FW, BWH, BD and BL, respectively. The presence of inbreeding depression but lack of dominance variance was consistent with an infinitesimal dominance model for the traits. The benefit of including non-additive genetic effects for genetic evaluations in tilapia breeding schemes is not evident from these findings, but the observed inbreeding depression points to a role for reciprocal recurrent selection. Commercially, this conclusion will depend on the scheme's operational costs and resources. The creation of maternal lines in Tilapia breeding schemes may be a possibility if the variation associated with maternal effects is heritable.


Cytologic diagnosis of aspergillosis in cardiac transplantation.
Fine-needle aspiration of the lung is now widely utilized to diagnose pulmonary neoplasms, but often serologic techniques or open-lung biopsy is relied on for the diagnosis of infectious pulmonary processes. We report a series of four patients in whom the fine-needle aspiration technique was used to make the rapid cytologic diagnosis of pulmonary aspergillosis. Culture confirmation was also obtained on the aspirated material. A discussion of the available techniques for the laboratory diagnosis of pulmonary aspergillosis is presented and the advantages of fine-needle aspiration cytology are stressed. Our favorable results support expanded use of fine-needle aspiration cytology in the evaluation of lung nodules appearing in immunosuppressed populations.


Kaptive Web: User-Friendly Capsule and Lipopolysaccharide Serotype Prediction for Klebsiella Genomes.
As whole-genome sequencing becomes an established component of the microbiologist's toolbox, it is imperative that researchers, clinical microbiologists, and public health professionals have access to genomic analysis tools for the rapid extraction of epidemiologically and clinically relevant information. For the Gram-negative hospital pathogens such as Klebsiella pneumoniae, initial efforts have focused on the detection and surveillance of antimicrobial resistance genes and clones. However, with the resurgence of interest in alternative infection control strategies targeting Klebsiella surface polysaccharides, the ability to extract information about these antigens is increasingly important. Here we present Kaptive Web, an online tool for the rapid typing of Klebsiella K and O loci, which encode the polysaccharide capsule and lipopolysaccharide O antigen, respectively. Kaptive Web enables users to upload and analyze genome assemblies in a web browser. The results can be downloaded in tabular format or explored in detail via the graphical interface, making it accessible for users at all levels of computational expertise. We demonstrate Kaptive Web's utility by analyzing >500 K. pneumoniae genomes. We identify extensive K and O locus diversity among 201 genomes belonging to the carbapenemase-associated clonal group 258 (25 K and 6 O loci). The characterization of a further 309 genomes indicated that such diversity is common among the multidrug-resistant clones and that these loci represent useful epidemiological markers for strain subtyping. These findings reinforce the need for rapid, reliable, and accessible typing methods such as Kaptive Web. Kaptive Web is available for use at http://kaptive.holtlab.net/, and the source code is available at https://github.com/kelwyres/Kaptive-Web.


Engineering Therapeutic T Cells: From Synthetic Biology to Clinical Trials.
Engineered T cells are currently in clinical trials to treat patients with cancer, solid organ transplants, and autoimmune diseases. However, the field is still in its infancy. The design, and manufacturing, of T cell therapies is not standardized and is performed mostly in academic settings by competing groups. Reliable methods to define dose and pharmacokinetics of T cell therapies need to be developed. As of mid-2016, there are no US Food and Drug Administration (FDA)-approved T cell therapeutics on the market, and FDA regulations are only slowly adapting to the new technologies. Further development of engineered T cell therapies requires advances in immunology, synthetic biology, manufacturing processes, and government regulation. In this review, we outline some of these challenges and discuss the contributions that pathologists can make to this emerging field.


Geographically linking population and facility surveys: methodological considerations.
The relationship between health services and population outcomes is an important area of public health research that requires bringing together data on outcomes and the relevant service environment. Linking independent, existing datasets geographically is potentially an efficient approach; however, it raises a number of methodological issues which have not been extensively explored. This sensitivity analysis explores the potential misclassification error introduced when a sample rather than a census of health facilities is used and when household survey clusters are geographically displaced for confidentiality. Using the 2007 Rwanda Service Provision Assessment (RSPA) of all public health facilities and the 2007-2008 Rwanda Interim Demographic and Health Survey (RIDHS), five health facility samples and five household cluster displacements were created to simulate typical SPA samples and household cluster datasets. Facility datasets were matched with cluster datasets to create 36 paired datasets. Four geographic techniques were employed to link clusters with facilities in each paired dataset. The links between clusters and facilities were operationalized by creating health service variables from the RSPA and attaching them to linked RIDHS clusters. Comparisons between the original facility census and undisplaced clusters dataset with the multiple samples and displaced clusters datasets enabled measurement of error due to sampling and displacement. Facility sampling produced larger misclassification errors than cluster displacement, underestimating access to services. Distance to the nearest facility was misclassified for over 50% of the clusters when directly linked, while linking to all facilities within an administrative boundary produced the lowest misclassification error. Measuring relative service environment produced equally poor results with over half of the clusters assigned to the incorrect quintile when linked with a sample of facilities and more than one-third misclassified due to displacement. At low levels of geographic disaggregation, linking independent facility samples and household clusters is not recommended. Linking facility census data with population data at the cluster level is possible, but misclassification errors associated with geographic displacement of clusters will bias estimates of relationships between service environment and health outcomes. The potential need to link facility and population-based data requires consideration when designing a facility survey.


Progress towards universal health coverage in BRICS: translating economic growth into better health.
Brazil, the Russian Federation, India, China and South Africa--the countries known as BRICS--represent some of the world's fastest growing large economies and nearly 40% of the world's population. Over the last two decades, BRICS have undertaken health-system reforms to make progress towards universal health coverage. This paper discusses three key aspects of these reforms: the role of government in financing health; the underlying motivation behind the reforms; and the value of the lessons learnt for non-BRICS countries. Although national governments have played a prominent role in the reforms, private financing constitutes a major share of health spending in BRICS. There is a reliance on direct expenditures in China and India and a substantial presence of private insurance in Brazil and South Africa. The Brazilian health reforms resulted from a political movement that made health a constitutional right, whereas those in China, India, the Russian Federation and South Africa were an attempt to improve the performance of the public system and reduce inequities in access. The move towards universal health coverage has been slow. In China and India, the reforms have not adequately addressed the issue of out-of-pocket payments. Negotiations between national and subnational entities have often been challenging but Brazil has been able to achieve good coordination between federal and state entities via a constitutional delineation of responsibility. In the Russian Federation, poor coordination has led to the fragmented pooling and inefficient use of resources. In mixed health systems it is essential to harness both public and private sector resources.


Postfragmentation density function for bacterial aggregates in laminar flow.
The postfragmentation probability density of daughter flocs is one of the least well-understood aspects of modeling flocculation. We use three-dimensional positional data of Klebsiella pneumoniae bacterial flocs in suspension and the knowledge of hydrodynamic properties of a laminar flow field to construct a probability density function of floc volumes after a fragmentation event. We provide computational results which predict that the primary fragmentation mechanism for large flocs is erosion. The postfragmentation probability density function has a strong dependence on the size of the original floc and indicates that most fragmentation events result in clumps of one to three bacteria eroding from the original floc. We also provide numerical evidence that exhaustive fragmentation yields a limiting density inconsistent with the log-normal density predicted in the literature, most likely due to the heterogeneous nature of K. pneumoniae flocs. To support our conclusions, artificial flocs were generated and display similar postfragmentation density and exhaustive fragmentation.


Prevalence of small opacities in chest radiographs of nickel sinter plant workers.
Radiographs from 745 nickel sinter plant workers were taken and classified by five readers using the International Labour Office (1980) protocol. Each reader worked independently and the films were randomly mixed with films from a non-dust exposed office population and also with films from subjects known to have silicosis or asbestosis. The prevalence of small irregular opacities was selected as the outcome of interest. In the sinter workers this was within the range identified in cigarette smokers or in workers exposed to dusts of low fibrogenicity. Only minimal evidence of small round opacities was noted. There was no evidence from the chest radiographs that exposures to high concentrations of dusts containing compounds of nickel caused an inflammatory or fibrogenic response in the lungs of the exposed population.


CO2-induced ocean acidification increases anxiety in rockfish via alteration of GABAA receptor functioning.
The average surface pH of the ocean is dropping at a rapid rate due to the dissolution of anthropogenic CO2, raising concerns for marine life. Additionally, some coastal areas periodically experience upwelling of CO2-enriched water with reduced pH. Previous research has demonstrated ocean acidification (OA)-induced changes in behavioural and sensory systems including olfaction, which is due to altered function of neural gamma-aminobutyric acid type A (GABAA) receptors. Here, we used a camera-based tracking software system to examine whether OA-dependent changes in GABAA receptors affect anxiety in juvenile Californian rockfish (Sebastes diploproa). Anxiety was estimated using behavioural tests that measure light/dark preference (scototaxis) and proximity to an object. After one week in OA conditions projected for the next century in the California shore (1125 ± 100 µatm, pH 7.75), anxiety was significantly increased relative to controls (483 ± 40 µatm CO2, pH 8.1). The GABAA-receptor agonist muscimol, but not the antagonist gabazine, caused a significant increase in anxiety consistent with altered Cl(-) flux in OA-exposed fish. OA-exposed fish remained more anxious even after 7 days back in control seawater; however, they resumed their normal behaviour by day 12. These results show that OA could severely alter rockfish behaviour; however, this effect is reversible.


Comparison of the use of regulatory assays and high-performance liquid chromatography for detection of residues of ceftiofur sodium metabolites in tissue specimens of culled dairy cattle.
To compare the results of regulatory screening and confirmation assays with those of high-performance liquid chromatography (HPLC) in the detection of ceftiofur metabolites in the tissues of culled dairy cattle. 17 lactating Holstein dairy cows. Daily IM injections of ceftiofur sodium were administered at a dose of 2.2 mg of ceftiofur equivalents/kg (n = 6) or 1.0 mg of ceftiofur equivalents/kg (10) for 5 days. Following withdrawal times of 12 hours (high-dose ceftiofur) and either 5 or 10 days (low-dose ceftiofur), cows were slaughtered and liver, kidney, and diaphragmatic muscle specimens were harvested and analyzed by HPLC and standard regulatory methods that included the following assays: the swab test on premises, the fast antimicrobial screen test, the calf antibiotic and sulfa test, and the 7-plate bioassay confirmation test. In all tissue specimens, residues of ceftiofur and desfuroylceftiofur-related metabolites, as measured by HPLC, were less than regulatory tolerance, as defined by the FDA. False-positive screening assay results were more likely for tissue specimens that had been frozen for shipment to a federal laboratory, compared with fresh tissue specimens that were assayed at the slaughter establishment (23% vs 3% false-positive results, respectively). The observation that fresh tissues had negative results on screening assays, whereas subsets of the same tissue specimens had false-positive results on screening assays following freezing, suggests that freezing and thawing interferes with microbial inhibition-based regulatory screening assays.


Ci-hox12 tail gradient precedes and participates in the control of the apoptotic-dependent tail regression during Ciona larva metamorphosis.
At the onset of the Ciona intestinalis metamorphosis, the first event is tail regression characterized, by a contraction, an apoptotic wave and Primordial Germ Cells (PGC) movement. All these cell behaviors originate from the posterior tail tip and progress to the anterior. Interestingly, earlier in Ciona development, the antero-posterior (A/P) patterning of the tailbud epidermis depends on two antagonist gradients, respectively FGF/MAPK at the posterior and retinoic acid (RA) at the anterior part of the tail. Fundamental genes such as Ci-hox1, Ci-hox12 and Ci-wnt5, classically involved in chordates A/P polarity and patterning, are controlled by these gradients and exhibit specific expression profiles in the tail epidermis. In this study, we first confirmed by video-microscopy that tail regression depends on a postero-anterior wave of a caspase-dependent apoptosis coupled with a contraction event. Concomitantly an apoptotic-dependent postero-anterior movement of PGC was observed for the first time. Unexpectedly, we observed that expression of the posterior hox gene, Ci-hox12, was extended from a posterior localization to the entire tail epidermis as the larvae progress from the swimming period to the settlement stage. In addition, when we disturbed FGF/MAPK or RA gradients we observed strong effects on Ci-hox12 expression pattern coupled with modulation on the subsequent tail regression dynamics. These results support the idea that Ci-hox12 expression in larval tail precedes and participates in the regulation of the postero-anterior cell behavior during the subsequent tail regression.


Conserved segmental expression of Krox-20 in the vertebrate hindbrain and its relationship to lineage restriction.
The zinc-finger gene Krox-20 is expressed in two alternating segments, rhombomeres (r) 3 and 5, in the developing mouse hindbrain. This expression pattern is established prior to rhombomere formation in the mouse, but it is not known how the timing of expression relates to cellular events of segmentation, such as lineage restriction. We have cloned Krox-20 sequences from Xenopus and the chick and shown that its alternating expression pattern is conserved in these systems, suggesting that its role in hindbrain development is conserved. Analysis of the early stages of Krox-20 expression in the chick show that both domains of expression precede the restriction of cell lineage to specific rhombomeres, consistent with a role of this gene in early events of hindbrain segmentation. The finding that expression is not coincident with lineage restriction indicates that early expression may not reflect an irreversible commitment of cells to r3 and r5 and/or may be mosaic.


Do documented records and retrospective reports of childhood maltreatment similarly predict chronic inflammation?
Childhood adversities have been associated with chronic inflammation and risk for cardiovascular disease. With some exceptions, existing knowledge of this relationship is based on retrospective self-reports, potentially subject to recall bias or memory problems. We seek to determine whether childhood maltreatment is associated with higher C-reactive protein (CRP) later in life and whether individuals with official and retrospective self-reports of maltreatment and men and women show similar increases in risk. Data are from in-person interviews in 2009-2010 with 443 offspring (mean age = 23.4) of parents in a longitudinal study of the consequences of childhood maltreatment. Official reports of maltreatment were abstracted from 2011-2013 Child Protective Services records. Eleven measures were used to assess self-reported maltreatment retrospectively. Seventeen percent of offspring had official reports, whereas self-reported prevalence rates ranged from 5.4% to 64.8%. CRP was assessed through blood spot samples. Regression models were used to estimate the effect of maltreatment on inflammation, adjusting for age, sex, race, parent occupational status, current depression, smoking, and heavy drinking. Individuals with official reports of child maltreatment and, specifically, physical abuse, had significantly higher levels of CRP than non-maltreated individuals. Maltreated females showed elevated CRP, independent of control variables, whereas no significant association was observed in males. Retrospective self-report measures of child maltreatment did not predict elevated CRP. Individuals with documented histories of childhood maltreatment are at increased risk for chronic inflammation and may benefit from targeted interventions. The results strengthen inferences about the effects of childhood maltreatment on inflammation in females.


Relapse after Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndromes: Analysis of Late Relapse Using Comparative Karyotype and Chromosome Genome Array Testing.
Relapse is a major cause of failure after allogeneic hematopoietic cell transplantation (HCT) in patients with myelodysplastic syndromes (MDS). We analyzed the relapse pattern in 1007 patients who underwent transplantation for MDS to identify factors that may determine the timing of relapse. Overall, 254 patients relapsed: 213 before 18 months and 41 later than 18 months after HCT, a time point frequently used in clinical trials. The hazard of relapse declined progressively with time since transplantation. A higher proportion of patients with early relapse had high-risk cytogenetics compared with patients with late relapse (P = .009). Patients with late relapse had suggestively longer postrelapse survival than patients who relapsed early, although the difference was not statistically significant (P = .07). Among 41 late relapsing patients, sequential cytogenetic data were available in 36. In 41% of these, new clonal abnormalities in addition to pre-HCT findings were identified at relapse; in 30% pre-HCT abnormalities were replaced by new clones, in 17.3% the same clone was present before HCT and at relapse, and in 9.7%, no abnormalities were present either before HCT or at relapse. Comparative chromosomal genomic array testing in 3 patients with late relapse showed molecular differences not detectable by cytogenetics between the pre-HCT clones and the clones at relapse. These data show that late relapses are not infrequent in patients who undergo transplantation for MDS. The pattern of new cytogenetic alterations at late relapse is similar to that observed in patients with early relapse and supports the concept that MDS relapse early and late after HCT is frequently due to the emergence of clones not detectable before HCT.


Evaluation of Spring Wheat Germplasm for Resistance to Bacterial Leaf Streak Caused by Xanthomonas campestris pv. translucens.
Bacterial leaf streak (caused by Xanthomonas campestris pv. translucens) has reemerged as a potential threat in spring wheat (Triticum aestivum) production areas in the northern Great Plains. As with other foliar bacterial diseases, chemical control under field situations is neither economical nor practical. Development of resistant genotypes will be needed for adequate management of the disease. There is currently limited information on sources of resistance in hard spring wheat germplasm. The main objective was to develop and apply a robust screening tool for evaluating germplasm against bacterial leaf streak, and to identify resistance sources for this disease. Inoculated field experiments were conducted in Brookings and Codington Counties, SD in 2009 and 2010 using a virulent local isolate (XctSD-017) inoculated after tillering stage. Forty-five hard red spring wheat genotypes with diverse genetic backgrounds were evaluated for disease severity, with ratings made at 7-day intervals from heading through dough stage. Results of this study showed clear differences in level of resistance among the 45 genotypes, with no immunity expressed. SD4205 was found resistant to the disease with the lowest area under the disease progress curve across location-years. Other genotypes showing moderate levels of resistance included SD4148, SD4176, 'Alsen', SD4023, 'Faller', SD4024, 'Knudson', and SD4199. Grain weight was negatively correlated to disease, as was days to heading. The resistance identified appeared to be quantitative in nature and was expressed through slower disease progress and reduced severity.


Multimorbidity, Polyiatrogenesis, and COVID-19.
To date, the strongest predictor for dying with COVID-19 is suffering from several chronic disorders prior to the viral infection. Pre-existing multimorbidity is highly correlated with socioeconomic inequality. In turn, having several chronic conditions is closely linked to multiple medication intake, especially in richer countries with good access to biomedical care. Owing to its vertical structure, biomedicine often risks giving multiple treatments in an uncoordinated way. Such lack of integrated care can create complex forms of iatrogenic harm. Multimorbidity is often exacerbated by a pharmaceuticalization of social deprivation in place of integrated care. In this article, I explore the possibility that clusters of over-medication are a contributing factor to higher death rates from COVID-19, especially in poorer areas within richer countries. Anthropological perspectives on the social embeddedness of multimorbidity and multiple medication use can expand our understanding of who is most vulnerable to SARS-CoV-2.


Socioeconomic and racial patterns of colorectal cancer screening among Medicare enrollees in 2000 to 2005.
Lower rates of screening among minorities and low-income populations contribute to colorectal cancer health disparities. Therefore, we examined patterns of colorectal cancer screening and associations with race-ethnicity, education, and income over time. Repeated cross-sectional data from the Medicare Current Beneficiary Survey of noninstitutionalized colorectal cancer-free Medicare enrollees ages 65 to 80 years interviewed in 2000 (n = 8,355), 2003 (n = 7,922), and 2005 (n = 7,646). We examined rates of colonoscopy/sigmoidoscopy use within 5 years (recent endoscopy), colonoscopy/sigmoidoscopy use >5 years previously, or fecal occult blood test (FOBT) within 2 years. Among those included in the analyses, there was a steady increase in recent endoscopy rates and decrease in FOBT use over the 6-year period among all racial, educational, and income groups. During each of the survey years, those less educated or in lower-income groups were less likely to undergo colorectal cancer screening in a dose-response fashion. In multinomial regression analyses that adjusted for factors including health insurance, there were no significant differences in recent endoscopy or FOBT rates between Blacks or Hispanics and Whites, but differences by education and income remained. Compared with those in higher-income group, lower-income enrollees had lower rates of screening, and differences by income were larger for enrollees residing in metropolitan areas. Among Medicare beneficiaries, there are persistent colorectal cancer screening disparities due to a complex combination of socioeconomic disadvantages from lower education and income, place of residence, and inadequate insurance. However, insurance alone does not eliminate socioeconomic differences in colorectal cancer screening.


Mechanisms of potentiation of mossy fiber EPSCs in the cerebellar nuclei by coincident synaptic excitation and inhibition.
Neurons of the cerebellar nuclei receive synaptic excitation from cerebellar mossy fibers. Unlike in many principal neurons, coincident presynaptic activity and postsynaptic depolarization do not generate long-term potentiation at these synapses. Instead, EPSCs are potentiated by high-frequency trains of presynaptic activity applied with postsynaptic hyperpolarization, in patterns resembling mossy-fiber-mediated excitation and Purkinje-cell-mediated inhibition that are predicted to occur during delay eyelid conditioning. Here, we have used electrophysiology and Ca imaging to test how synaptic excitation and inhibition interact to generate long-lasting synaptic plasticity in nuclear cells in cerebellar slices. We find that the extent of plasticity varies with the relative timing of synaptic excitation and hyperpolarization. Potentiation is most effective when synaptic stimuli precede the postinhibitory rebound by approximately 400 ms, whereas with longer intervals, or with a reverse sequence, EPSCs tend to depress. When basal intracellular Ca is raised by spontaneous firing or reduced by voltage clamping at subthreshold potentials, potentiation is induced as long as the synaptic-rebound temporal sequence is maintained, suggesting that plasticity does not require Ca levels to exceed a threshold or attain a specific concentration. Although rebound and spike-dependent Ca influx are global, potentiation is synapse specific, and is disrupted by inhibitors of calcineurin or Ca-calmodulin-dependent protein kinase II, but not PKC. When IPSPs replace the hyperpolarizing step in the induction protocol, potentiation proceeds normally. These results lead us to propose that synaptic and inhibitory/rebound stimuli initiate separate processes, with local NMDA receptor-mediated Ca influx "priming" synapses, and Ca changes from the inhibition and rebound "triggering" potentiation at recently activated synapses.


Prevalence and characteristics associated with self-reported gall bladder disease in Mexican American elders: results from the Hispanic Established Populations for Epidemiologic Studies in the Elderly (H-EPESE).
To identify the prevalence and characteristics of gall bladder disease (GBD) that has been self-reported in Mexican American Elders. A prospective survey of a regional probability sample of self-identified Mexican Americans aged 65 and over. The Hispanic Established Population for the Epidemiologic Studies of the Elderly (H-EPESE), a probability sample of non-institutionalized, Mexican Americans, aged 65 and over, residing in Southwestern states of Texas, New Mexico, Colorado, Arizona, and California. In 1993- 1994 (Wave 1), 3050 Mexican Americans, aged 65 and over, were selected at baseline as a weighted probability sample. In 1995-1996 (Wave 2), 2895 remained. Sample weights were used to extrapolate to the estimated 498,176 older Mexican Americans residing in the Southwest United States. Self-reported GBD was collected via in-home interviews. The prevalence of self-reported GBD in Mexican American elders was found to be 18.8% with an average age of 75.05 years. The findings indicate that older Mexican Americans have an increased rate of GBD if they are female, have history of arthritis or hypertension and have more acculturation to the United States. However, the rate decreases when they score poorly on the Mini Mental State Exam. One major limitation was reliance on self-report, as GBD and other co-morbid illnesses may be under-, or overestimated. Age is not protective in the prevalence of GBD in elder Mexican Americans. Persistent underlying genetics and dietary habits most likely attribute to this consistent high percentage, even in the elderly.


Linear, planar and spherical tensor-valued diffusion MRI data by free waveform encoding in healthy brain, water, oil and liquid crystals.
Recently, several biophysical models and signal representations have been proposed for microstructure imaging based on tensor-valued, or multidimensional, diffusion MRI. The acquisition of the necessary data requires non-conventional pulse sequences, and data is therefore not available to the wider diffusion MRI community. To facilitate exploration and development of analysis techniques based on tensor-valued diffusion encoding, we share a comprehensive data set acquired in a healthy human brain. The data encompasses diffusion weighted images using linear, planar and spherical diffusion tensor encoding at multiple b-values and diffusion encoding directions. We also supply data acquired in several phantoms that may support validation. The data is hosted by GitHub: https://github.com/filip-szczepankiewicz/Szczepankiewicz_DIB_2019.


Internet-delivered cognitive behavioural therapy for perfectionism: Targeting dysmorphic concern.
Perfectionism is an important transdiagnostic risk factor for several psychopathologies. As such, treatments targeting perfectionism have gained increased attention over recent years. While perfectionism is postulated to be an important underlying mechanism for dysmorphic concern, no research has explored the benefits of targeting perfectionism to reduce dysmorphic concern. The current study evaluated the use of Internet-delivered cognitive behavioural therapy for perfectionism (ICBT-P) with 31 participants (28 women) with high levels of dysmorphic concern to examine the impact on perfectionism, dysmorphic concern, body image disturbance, negative affect, and selective attention towards appearance-based stimuli. Using a case series design, observations were collected at baseline, at the end of a 4-week pre-treatment phase, after the 8-week ICBT-P, and 1-month post-treatment. Intent-to-treat analyses showed significant improvement from baseline to end-of-treatment and follow-up on most of the variables, with a large effect size decrease in dysmorphic concern, and decreased selective attention to BDD-body, BDD-positive, and BDD-negative words. The results of this study support the use of ICBT-P as an efficacious treatment worthy of further examination in populations who experience high levels of dysmorphic concern.


The anomalous Hall effect and magnetic monopoles in momentum space.
Efforts to find the magnetic monopole in real space have been made in cosmic rays and in particle accelerators, but there has not yet been any firm evidence for its existence because of its very heavy mass, approximately 10(16) giga-electron volts. We show that the magnetic monopole can appear in the crystal momentum space of solids in the accessible low-energy region (approximately 0.1 to 1 electron volts) in the context of the anomalous Hall effect. We report experimental results together with first-principles calculations on the ferromagnetic crystal SrRuO3 that provide evidence for the magnetic monopole in the crystal momentum space.


Perceptions of smoking-related risk and worry among dual-smoker couples.
Quit rates are lower and relapse rates are higher for people in close relationships with a partner who smokes. Although desire to quit is often related to health concerns for one's self, much less is known about psychosocial factors associated with quitting in dual-smoker couples. This study investigated relations among beliefs about smoking and desire to quit from both partners' perspectives. We recruited 63 couples in which both partners smoke daily. Participants were aged 21-67 (M = 43.0, SD = 11.3) and had been smoking for 4-51 years (M = 22.9, SD = 11.3). Individuals' desire to quit related to worry about partner's health (r = .29, p < .01), perceived risk of partner getting a disease if the partner continues to smoke (r = .39, p < .001), and belief that own smoking has caused partner physical harm (r = .38, p < .001). Within couples, partners were modestly concordant with regard to worry about harm of smoking for oneself (r = .30, p < .05) and partner (r = .30, p < .05), perceived risk of disease for oneself (r = .26, p < .05) and partner (r = .24, p < .05), and desire that partner quit (r = .34, p < .01). Participants had an extremely strong desire (78% = 7 on 1-7 scale) for their partner's help if they attempt to quit. Dual-smoker couples are at heightened health risks due to exposure to passive smoke and their own smoking. Partners' perceived risk and worry about the harms of smoking could be important leverage points for smoking cessation efforts. Interventions can be informed by considering both partners' beliefs and by helping partners develop plans for quitting and supporting each other.


Bayesian community detection.
Many networks of scientific interest naturally decompose into clusters or communities with comparatively fewer external than internal links; however, current Bayesian models of network communities do not exert this intuitive notion of communities. We formulate a nonparametric Bayesian model for community detection consistent with an intuitive definition of communities and present a Markov chain Monte Carlo procedure for inferring the community structure. A Matlab toolbox with the proposed inference procedure is available for download. On synthetic and real networks, our model detects communities consistent with ground truth, and on real networks, it outperforms existing approaches in predicting missing links. This suggests that community structure is an important structural property of networks that should be explicitly modeled.


Structures of potent anticancer compounds bound to tubulin.
Small molecules that bind to tubulin exert powerful effects on cell division and apoptosis (programmed cell death). Cell-based high-throughput screening combined with chemo/bioinformatic and biochemical analyses recently revealed a novel compound MI-181 as a potent mitotic inhibitor with heightened activity towards melanomas. MI-181 causes tubulin depolymerization, activates the spindle assembly checkpoint arresting cells in mitosis, and induces apoptotic cell death. C2 is an unrelated compound previously shown to have lethal effects on microtubules in tumorigenic cell lines. We report 2.60 Å and 3.75 Å resolution structures of MI-181 and C2, respectively, bound to a ternary complex of αβ-tubulin, the tubulin-binding protein stathmin, and tubulin tyrosine ligase. In the first of these structures, our crystallographic results reveal a unique binding mode for MI-181 extending unusually deep into the well-studied colchicine-binding site on β-tubulin. In the second structure the C2 compound occupies the colchicine-binding site on β-tubulin with two chemical moieties recapitulating contacts made by colchicine, in combination with another system of atomic contacts. These insights reveal the source of the observed effects of MI-181 and C2 on microtubules, mitosis, and cultured cancer cell lines. The structural details of the interaction between tubulin and the described compounds may guide the development of improved derivative compounds as therapeutic candidates or molecular probes to study cancer cell division.


Multiple Unerupted Permanent Teeth Associated with Noonan Syndrome.
The present report describes a case of Noonan's syndrome from a dental viewpoint. Noonan syndrome is an autosomal dominant multisystem disorder. Congenital heart deformities, short stature, thoracic deformities, short neck with webbing, hypertelorism, and malocclusions are some of the frequently observed clinical features. Atypical dental anomalies such as multiple unerupted permanent teeth, multiple submerged and retained deciduous teeth, and supernumerary teeth were found in the present case. Oral prophylaxis and preventive resin restorations were done following which the supernumerary teeth were extracted. 54, 55, 64, 65, 74, 75 and 84 were extracted after orthodontic consultation to facilitate the eruption of permanent teeth. The patient is undergoing fixed orthodontic therapy for forced eruption of unerupted permanent teeth. General dentists should correlate dental anomalies with other systemic features in the diagnosis of such syndromes because of the variability in presentation and the need for multidisciplinary care.


Randomized controlled study of probiotics containing Lactobacillus casei (Shirota strain) for prevention of ventilator-associated pneumonia.
To evaluate the efficacy ofprobiotics, Lactobacillus casei (Shirvta strain), in reducing the incidence ofventilator- associated pneumonia (VAP) in medical patients who received mechanical ventilation at Siriraj Hospital. A prospective, randomized, open-label controlled trial was conducted in 150 adult hospitalized patients in medical wards who were expected to receive mechanical ventilation for 72 hours or longer: The patients were randomized to the probiotics group or the control group. All patients received regular care for mechanical ventilation. The patients in the probiotics group received 80 ml of Lactobacillus casei (Shirota strain) for oral care after having standard oral care once daily and additional 80 ml of the aforementionedfermented dairy product was given via enteralfeeding once daily. The primary outcomes were incidence of VAP and incidence rate of VAP episodes per 1,000 ventilator-days. The secondary outcomes were length ofhospital stay, mortality at day 28 and 90, incidence ofdiarrhea, andpresence of resistant bacteria in oropharyngeal and rectal swab samples taken from the patients at baseline, day 7 and day 28 after enrollment. The baseline characteristics of the patients in the probiotics group (75) and the control group (75) were not significantly different. The patients in the probiotics group were less likely to develop VAP compared with the control group (24% vs. 29.3%, p = 0.46), respectively. The incidence rates of VAP in the probiotics and control groups were 22.64 and 30.22 episodes per 1,000 ventilator-days, respectively (p = 0.37). A trend of lower prevalence of some resistant bacteria cultured from oropharyngeal swabs in the probiotics group than that in the control group was observed. Overall 28- and 90-day mortality and length of hospital stay of the patients in both groups were not significantly different. Administration of probiotics containing Lactobacillus casei (Shirota strain) has a tendency to reduce the incidence of VAP and colonization with resistant bacteria in oropharyngeal cavity without significant effects on mortality and length of hospital stay.


Interaction of amphiphilic coumarin with DPPC/DPPS lipid bilayer: effects of concentration and alkyl tail length.
In this work, interactions between amphiphilic amino methyl coumarin and dipalmitoyl-sn-glycero-3-phosphocholine/dipalmitoyl-sn-glycero-3-phosphoserine (DPPC/DPPS) lipid bilayer were investigated. A combination of experimental techniques (zeta potential, fluorescence spectroscopy, and differential scanning calorimetry) along with molecular dynamics simulations was employed to examine the influence of alkyl tail length and concentration of the amphiphilic coumarin on the lipid bilayer. Alkyl tails comprising 5(C5), 9(C9), and 12(C12) carbon atoms were conjugated to amino methyl coumarin via a single-step process. The binding and insertion mechanisms of the amphiphilic coumarins were studied in increasing concentrations for short-tailed (C5) and long-tailed (C12) coumarins. The simulation results show that C5 coumarin molecules penetrate the lipid bilayer, but owing to the short alkyl tail, they interact primarily with the lipid head groups resulting in lipid bilayer thinning; however, at high concentrations, the C5 coumarins undergo continuous insertion-ejection from the outer leaflet of the lipid bilayer. In contrast, C12 coumarins interact favorably with the hydrophobic lipid tails and lack the ejection-reinsertion behavior. Instead, the C12 coumarin molecules undergo flip-flops between the outer and inner leaflets of the lipid bilayer. At high concentrations, the high-frequency flip-flops lead to lipid destabilization, causing the lipid bilayer to rupture. The simulation results are in excellent agreement with the toxicity of amphiphilic coumarin activity in cancer cells. The efficacy of amphiphilic coumarins in liposomal lipid bilayers demonstrates the promise of these molecules as a tool in the treatment of cancer.


The virtual dental home: bringing oral health to vulnerable and underserved populations.
Large and increasing oral health disparities in the U.S. population led the Institute of Medicine to call for expanded research and demonstration of delivery systems that test new methods and technologies. These new methods include delivering oral health services in nontraditional settings, using nondental professionals, expanded roles for existing dental professionals and new types of dental professionals, and incorporating telehealth technologies. The virtual dental home is a system that demonstrates the characteristics called for by the IOM.


Loss of detectability and indeterminate results: Challenges facing HIV infant diagnosis in South Africa's expanding ART programme.
Early infant diagnosis with rapid access to treatment has been found to reduce HIV-associated infant mortality and morbidity considerably. In line with international standards, current South African guidelines advocate routine HIV-1 polymerase chain reaction (PCR) testing at 6 weeks of age for all HIV-exposed infants and 'fast-track' entry into the HIV treatment programme for those who test positive. Importantly, testing occurs within the context of increasing efforts at prevention of mother-to-child transmission (PMTCT) by means of maternal and infant antiretroviral therapy (ART). In addition, infants already initiated on combination ART (cART) may be retested with PCR assays for 'confirmatory' purposes, including assessment prior to adoption. The potential for cART to compromise the sensitivity of HIV-1 PCR assays has been described, although there are limited and conflicting data regarding the effect of PMTCT regimens on HIV-1 PCR diagnostic sensitivity. We describe a case series of three infants with different ART exposures in whom HIV diagnosis, confirmation or the result of retesting for adoption purposes were uncertain. These cases demonstrate that ART can be associated with a loss of detectability of HIV, leading to 'false-negative' HIV-1 PCR results in infants on cART. Furthermore, current PMTCT practices may lead to repeatedly indeterminate results with a subsequent delay in initiation of cART. The sensitivity of HIV-1 PCR assays needs to be re-evaluated within the context of different ART exposures, and diagnostic algorithms should be reviewed accordingly.


Effects of Legislation Regulating Abortion in Arizona.
Abortion is a common and safe procedure in the United States, the regulation of which varies by state. Since 2011, hundreds of state-level abortion restrictions have been enacted by legislatures across the country. This study describes the effects of two such regulations enacted in 2011 in Arizona, (A.R.S.) 36-2153 and 36-2155, that imposed a 24-hour waiting period requiring two separate in-person clinic visits before obtaining an abortion and banned advanced practice clinicians such as physician assistants, nurse practitioners, and nurse midwives from inducing medication abortions by prescribing mifepristone. We conducted a pre-post study to describe the effect of Arizona's scope of practice law on abortion provision by county. Using publicly available data, we compared patterns of abortion provision in 2009 and 2010 (before the laws) with 2012 and 2013. Our primary objective was to compare the proportion of abortions performed with medication by prescription of mifepristone (versus abortions performed surgically, known as aspiration abortions) before and after the laws were enacted. Our secondary objectives were to report the number of counties that lost an abortion provider and the change in the proportion of abortions performed before 14 weeks' gestation of pregnancy after the enactment of the laws. After enactment of the laws, the proportion of Arizona's 15 counties with abortion clinics decreased from 33% to 13%. Over this time, the proportion of abortions performed with medication in Arizona decreased by 17.4% (95% CI, 16.6%-18.3%; p = .0002), from 47.6% to 30.2%. Similarly, the proportion of abortions performed before 14 weeks' gestation in Arizona decreased by 3.3% (95% CI, 2.8%-3.8%; p = .0002) after the enactment of these laws. The proportion of abortions performed with medication and the proportion of abortion performed before 14 weeks' gestation in Arizona were negatively affected by the enactment of these laws. These findings are not explained by national temporal trends in abortion, because the proportion of abortions performed with medication increased and early abortions remained stable over the same time period in the United States as a whole. Proponents of laws restricting the provision of abortion such as these claim to improve the safety of abortion, but they actually seem to decrease access to abortion, as defined by the number of counties with abortion providers, and subsequently lead to delays in abortion. These data should inform future policies by providing an example of how such laws affect women seeking abortion.


Most nursing home social service directors lack training in working with lesbian, gay, and bisexual residents.
The purpose of this descriptive study is to report findings from a nationally representative mail-in survey of nursing home social service directors (n = 1,071) who were asked if they had received at least one hour of training in six different areas of cultural competency in the past five years. Of the six areas, the lowest percentage of directors reported having training in homophobia. Three-fourths of the sample had not received even one hour of homophobia training over the past five years. Directors who were more recently educated were more likely to report having received homophobia training, as were directors with a college degree, and those who worked in nursing homes located in the West and South regions of the United States. Directors with the most experience were less likely to report having received training. Findings call for immediate development and dissemination of heterosexism and homophobia training of social service staff, policy changes within the nursing home, and policy advocacy priorities for social workers.


Mycobacterium avium subspecies paratuberculosis cultured from locally and commercially pasteurized cow's milk in the Czech Republic.
Between November 2002 and April 2003, 244 bottles and cartons of commercially pasteurized cow's milk were obtained at random from retail outlets throughout the Czech Republic. During the same period, samples of raw milk and of milk that was subsequently subjected to a minimum of 71.7 degrees C for 15 s in a local pasteurization unit were also obtained from two dairy herds, designated herds A and B, with low and high levels, respectively, of subclinical Mycobacterium avium subsp. paratuberculosis infection, and from one herd, herd C, without infection. Infection in individual cows in each herd was tested by fecal culturing. Milk samples were brought to the Veterinary Research Institute in Brno, Czech Republic, processed, inoculated onto Herrold's egg yolk slants, and incubated for 32 weeks. Colonies were characterized by morphology, Ziehl-Neelsen staining, mycobactin J dependency, and IS900 PCR results. M. avium subsp. paratuberculosis was cultured from 4 of 244 units (1.6%) of commercially pasteurized retail milk. M. avium subsp. paratuberculosis was also cultured from 2 of 100 (2%) cartons of locally pasteurized milk derived from infected herds A and B and from 0 of 100 cartons of milk from uninfected herd C. Raw milk from 1 of 10 (10%) fecal culture-positive cows in herd A and from 13 of 66 (19.7%) fecal culture-positive cows in herd B was culture positive for M. avium subsp. paratuberculosis. These findings confirm that M. avium subsp. paratuberculosis is present in raw milk from subclinically infected dairy cows. The culture of M. avium subsp. paratuberculosis in the Czech Republic from retail milk that had been pasteurized locally or commercially to the required national and European Union standards is in agreement with similar research on milk destined for consumers in the United Kingdom and the United States and shows that humans are being exposed to this chronic enteric pathogen by this route.


Telmisartan versus valsartan in patients with hypertension: effects on cardiovascular, metabolic, and inflammatory parameters.
Angiotensin-receptor blockers (ARBs) have beneficial effects on cardiovascular, metabolic, and inflammatory parameters in addition to controlling blood pressure (BP). However, few comparative clinical studies have been conducted with different ARBs. We compared these effects in patients with uncomplicated hypertension who were receiving telmisartan or valsartan. The subjects were patients with essential hypertension (48.4±9.6 years) who were randomly assigned to take either telmisartan (80 mg/day, n=30) or valsartan (160 mg/day, n=30) for 12 weeks. Their anthropometric, laboratory, vascular, and echocardiographic data were measured at baseline and at the end of the study. Baseline characteristics were not significantly different between the two groups, except for the carotid-femoral pulse wave velocity (cfPWV; telmisartan group vs. valsartan group; 841.2±131.0 vs. 761.1±104.4 cm/s, p<0.05). After 12 weeks, BP had fallen to a similar extent with mean reductions in the systolic and diastolic BP of 20.7±18.1 and 16.3±13.0 mm Hg (p<0.001, respectively) for the telmisartan and 22.5±17.0 and 16.8±9.3 mm Hg (p<0.001, respectively) for the valsartan group. Although the cfPWV and left ventricular mass index (LVMI) fell significantly only with the administration of telmisartan, they were not significantly different when baseline cfPWV was considered. The differences in the cfPWV and LVMI changes from baseline between the two groups were also not significant after adjusting for baseline cfPWV. No significant changes in other vascular, metabolic, or inflammatory parameters were observed with either treatment. The effects of a 12-week treatment with the two ARBs, telmisartan and valsartan, on cardiovascular, metabolic, and inflammatory parameters were not different in patients with uncomplicated hypertension.


Molecular docking and structure-based virtual screening studies of potential drug target, CAAX prenyl proteases, of Leishmania donovani.
Targeting CAAX prenyl proteases of Leishmania donovani can be a good approach towards developing a drug molecule against Leishmaniasis. We have modeled the structure of CAAX prenyl protease I and II of L. donovani, using homology modeling approach. The structures were further validated using Ramachandran plot and ProSA. Active site prediction has shown difference in the amino acid residues present at the active site of CAAX prenyl protease I and CAAX prenyl protease II. The electrostatic potential surface of the CAAX prenyl protease I and II has revealed that CAAX prenyl protease I has more electropositive and electronegative potentials as compared CAAX prenyl protease II suggesting significant difference in their activity. Molecular docking with known bisubstrate analog inhibitors of protein farnesyl transferase and peptidyl (acyloxy) methyl ketones reveals significant binding of these molecules with CAAX prenyl protease I, but comparatively less binding with CAAX prenyl protease II. New and potent inhibitors were also found using structure-based virtual screening. The best docked compounds obtained from virtual screening were subjected to induced fit docking to get best docked configurations. Prediction of drug-like characteristics has revealed that the best docked compounds are in line with Lipinski's rule. Moreover, best docked protein-ligand complexes of CAAX prenyl protease I and II are found to be stable throughout 20 ns simulation. Overall, the study has identified potent drug molecules targeting CAAX prenyl protease I and II of L. donovani whose drug candidature can be verified further using biochemical and cellular studies.


Barriers to Breastfeeding: Supporting Initiation and Continuation of Breastfeeding: ACOG Committee Opinion, Number 821.
Breastfeeding has maternal, infant, and societal benefits. However, many parents experience obstacles to achieving their breastfeeding goals, leading to reduced rates of breastfeeding initiation and continuation. Despite efforts to increase rates of breastfeeding initiation and continuation, inequities still persist. The factors that influence an individual's desire and ability to breastfeed are varied and include individual parent considerations; practitioner influences; hospital barriers; societal factors, such as workplace and parental leave policies; access to lactation support; and social support of their breastfeeding goals. A multidisciplinary approach that involves community, family, parents, and health care professionals will strengthen the support for parents and help them achieve their breastfeeding goals.


High-power Yb-doped photonic bandgap fiber amplifier at 1150-1200 nm.
Ytterbium-doped solid-core photonic bandgap fiber amplifiers operating at the long-wavelength edge of the ytterbium gain band are reported. The low-loss bandgap transmission window is formed in the very low gain region, whilst outside the bandgap, large attenuation inhibits the exponential growth of amplified spontaneous emission in the huge-gain 1030-1100 nm region. Hence parasitic-lasing-free, high-power amplification with a marked efficiency is enabled. A 32 W output at 1156 nm with a 66% slope efficiency and 30 W output at 1178 nm with a 58% slope efficiency were successfully obtained. To our knowledge, these are the highest output powers generating from active photonic bandgap fibers, as well as from ytterbium-doped fiber lasers at these wavelengths.


Effect of ethanolic extract of Cassia occidentalis Linn. for the management of alloxan-induced diabetic rats.
As per traditional claims, root, bark, leaf and flower of the plant Cassia occidentalis Linn. (Caesalpiniaceae) have been reported to possess antidiabetic activity. Based on this traditional indication, the aim of this study was to evaluate the antidiabetic activity of ethanolic extract of C. occidentalis in normal and alloxan induced diabetic rats. Ethanolic extract of the whole plant of C. occidentalis was orally tested at doses of 100 and 200 mg/kg for evaluating the hypoglycemic effect in normal and alloxan-induced diabetic rats. In addition, changes in body weight, serum cholesterol, triglyceride and total protein levels, assessed in the ethanol extract treated diabetic rats were compared with diabetic control and normal animals. Histopathologic observations during 21 days of treatment were also evaluated. Ethanolic extract of C. occidentalis produced a significant reduction in fasting blood glucose levels in the normal and alloxan-induced diabetic rats at doses of 100 and 200 mg/kg body weight. Treatment with ethanolic extract of C. occidentalis in normal and alloxan-induced diabetic rats led to a dose-dependent fall in blood sugar levels. Significant differences were observed in serum lipid profiles (cholesterol and triglyceride), serum protein and changes in body weight in ethanolic extract treated diabetic animals, when compared with the diabetic control and normal animals. Concurrent histopathologic studies of the pancreas of these animals showed comparable regeneration by ethanolic extract, which were earlier necrosed by alloxan. Ethanolic extract of C. occidentalis exhibited significant antidiabetic activity in normal and alloxan-induced diabetic rats. The rats also showed improvement in parameters like body weight and lipid profiles and also, histopathologic studies showed regeneration of β-cells of pancreas and so it might be of value in the treatment of diabetes.


Effect of chronic experimental diabetes on vascular smooth muscle function in rabbit carotid artery.
To understand the effects of diabetes on vascular smooth muscle function and the underlying mechanism(s) involved, we examined the responses to alpha-adrenoceptor agents, serotonin (5-HT), K+, and prostaglandins in the carotid artery of male New Zealand white rabbits with chronic diabetes (16 weeks) induced chemically by alloxan (100 mg/kg, intravenously) treatment. Isolated ring segments of diabetic rabbit carotid artery exhibited an increased (20-60%) maximal response to norepinephrine (NE), methoxamine, phenylephrine, and K+ as compared with controls. Responses to 5-HT were not significantly increased. Nevertheless, there were no significant differences in ED50 values of the agonists in either of the groups. Putatively selective alpha 2-adrenoceptor agonists (clonidine and guanabenz), prostaglandin E1 (PGE1) and prostaglandin I2 (PGI2) did not elicit any response in control vessels. In the diabetic state, however, these drugs contracted the artery in a dose-dependent fashion. Isoproterenol (0.1-10 microM) relaxed arterial rings previously contracted with all the agonists except PGE1 and PGI2, which were potentiated by isoproterenol. Contractions to PGE1 or PGI2 alone or in the presence of isoproterenol were reduced or abolished by 10(-5) M phentolamine. Under these conditions, isoproterenol exhibited its typical relaxatory action. Nifedipine was more potent in inhibiting the K+ response in diabetic carotid artery than in the controls. These results suggest an increased reactivity of diabetic rabbit carotid artery to alpha 2-adrenoceptor agonists, K+, PGE1, and PGI2 which may, at least in part, be due to an increased sensitivity of calcium channels in diabetic vessels. Contractile responses to PGE1 and PGI2 could be attributed to their action on adrenergic neurotransmission, thereby facilitating the release of NE from presynaptic nerve terminals. Furthermore, isoproterenol at a high dose (1 microM or more) may directly stimulate alpha-adrenoceptors. Whether or not this effect of isoproterenol is only prostaglandin-dependent is not clear.


Effect of titanium or zirconia implant abutments on epithelial attachments after ultrasonic cleaning.
Zirconia is widely employed as a material during dental implant work because of its superior esthetics. This study sought to evaluate the impact of titanium or zirconia implant abutments on epithelial attachments after ultrasonic cleaning. These implants were inserted into the extraction socket of rat maxillary first molars. Then, the length of the horseradish peroxidase (HRP) reaction was measured. In addition, titanium and zirconia disks were cleaned using an ultrasonic scaler, surface morphology changes were observed, and the number of epithelial cell attachments to the surface was measured. Ultimately, the surfaces of the titanium disks were easier to damage than those of the zirconia ones. There was no difference in the number of epithelial cell attachments between the two materials with the ultrasonic cleaning. The length of the HRP reaction was shorter on the zirconia implant abutment surface than on the titanium one after mechanical cleaning. In conclusion, zirconia is harder than titanium and a better choice for use in the epithelial tissue attachment. Zirconia is more suitable as a material for implant abutments than titanium.


Application of power Doppler vocal fremitus sonography in breast lesions.
The purpose of this study was to illustrate the method and use of power Doppler vocal fremitus (PDVF) sonography in the detection and diagnosis of breast lesions. One case was evaluated by various sonographic parameters and equipment to determine how the VF images were affected. Cases illustrative of a broad range of breast conditions were also collected. Each image pair consisted of B-mode and VF images to maintain an identical projection and to illustrate the influence of PDVF sonography. With B-mode and PDVF sonography, we evaluated and compared various breast conditions, including normal anatomic structures and abnormal lesions. We found that PDVF sonography is useful for distinguishing abnormal masses from normal tissue, such as differentiating between isoechoic tumors and isoechoic glandular tissues, and discriminating entrapped fat lobules from isoechoic tumors. Furthermore, PDVF sonography was useful for determining whether intracystic echoes are attached to the cyst wall. Power Doppler VF imaging is a valuable adjunct tool to B-mode sonography in the evaluation of breast lesions.


Evaluation of GoGirlGo!; A practitioner based program to improve physical activity.
GoGirlGo! (GGG) is designed to increase girls' physical activity (PA) using a health behavior and PA-based curriculum and is widely available for free to afterschool programs across the nation. However, GGG has not been formally evaluated. The purpose of this pilot study was to evaluate the effectiveness of the GGG curricula to improve PA, and self-efficacy for and enjoyment of PA in elementary aged girls (i.e., 5-13 years). Nine afterschool programs were recruited to participate in the pilot (within subjects repeated measures design). GGG is a 12-week program, with a once a week, one-hour lesson with 30 minutes of education and 30 minutes of PA). Data collection occurred at baseline, mid (twice), post, and at follow-up (3-months after the intervention ended). PA was assessed via accelerometry at each time point. Self-efficacy for and enjoyment of PA was measured using the Self-Efficacy Scale and the Short-PA enjoyment scale and was assessed at baseline, post, and follow-up. Fidelity was assessed at midpoint. Across all age groups there was a statistically significant increase in PA. Overall, on days GGG was offered girls accumulated an average of 11 minutes of moderate-to-vigorous PA compared to 8 minutes during non-GGG days. There was a statistically significant difference in girls' self-efficacy for PA reported between baseline and post, which was maintained at follow-up. An improvement in enjoyment of PA for girls was found between baseline and follow-up. According to fidelity assessment, 89% of the activities within the curriculum were completed each lesson. Girls appeared to respond well to the curriculum but girls 5-7 years had difficulties paying attention and understanding discussion questions. Even though there were statistically significant differences in self-efficacy for PA and enjoyment of PA, minimal increases in girls' PA were observed. GGG curricula improvements are warranted. Future GGG programming should explore offering GGG every day, modifying activities so that they are moderate-to-vigorous in intensity, and providing additional trainings that allow staff to better implement PA and improve behavior management techniques. With modifications, GGG could provide a promising no-cost curriculum that afterschool programs may implement to help girls achieve recommendations for PA.


Changes in the electrical properties of supraoptic nucleus oxytocin and vasopressin neurons during lactation.
Magnocellular oxytocin (OT) and vasopressin (VP) neurons adopt different firing patterns in response to relevant physiological stimuli. OT neurons selectively display short (2-4 sec), high-frequency bursts of action potentials that are highly synchronized and correlated with OT release during lactation. The present experiments were done to determine whether the electrophysiological properties of OT neurons differ from those of VP neurons, and whether these properties are modulated during lactation to support short bursting activity. Intracellular recordings in vitro were obtained from immunochemically identified supraoptic neurons of diestrous or lactating female rats. Resting membrane potential, input resistance, membrane time constant, and the depolarizing afterpotential did not differ among groups. However, near spike threshold, OT, but not VP, neurons expressed a sustained outward rectification that was removed by small hyperpolarizing pulses and a rebound depolarization that occurred at the offset of these hyperpolarizing pulses. The rebound depolarization was short ( < 2 sec), supported brief bursts of action potentials, and was significantly larger during lactation. Neurons expressing the outward rectification also exhibited strong spike frequency adaptation during prolonged (1-4 sec) depolarization. Spike width, the Ca(2+)- dependent afterhyperpolarization, and the degree of spike broadening of OT, but not VP, neurons were also larger during lactation, suggesting an increase in Ca2+ influx per spike. The results indicate that OT neurons possess properties favoring the expression of short spike trains, and that some of these properties are enhanced during lactation. In addition, spikes in OT neurons may promote more Ca2+ influx in this state.


Seroprevalence of measles IgG among HIV-1-infected and uninfected Kenyan adults.
Despite global efforts to reduce measles incidence, outbreaks continue to occur in developing countries where HIV-1-infected adults represent a vulnerable population. Immunization campaigns have targeted children, although little is known about the levels of measles protection in adult populations in Kenya. The objective of this study was to determine seroprevalence and titers of measles IgG among HIV-1-infected and uninfected adults in Nairobi, Kenya. The presence of anti-measles IgG was measured in cryopreserved serum of 257 HIV-1-infected and 367 uninfected adults using a commercial ELISA (Enzygnost, Germany). The measles IgG concentration was calculated for those samples that were positive. Overall, 96% of adults were measles seropositive and the mean measles IgG concentration among those who were seropositive was 4134 mIU/ml, which is well above previously reported protective levels. There was no statistical difference in seroprevalence or antibody concentration between the HIV-infected and HIV-uninfected groups. While local vaccination efforts and circulating measles infection likely contribute to this high measles seroprevalence rate, these data are unique to an urban population and may not reflect a country-wide distribution. Our results suggest that reduced immunity among HIV-1-infected adults is not a major contributor to measles resurgence in Kenya.


The association between serine hydroxymethyl transferase 1 gene hypermethylation and ischemic stroke.
This study aimed to determine the correlation between serine hydroxymethyl transferase 1 (SHMT1) gene methylation and ischemic stroke. A total of 202 age- and sex-matched individuals were included. Quantitative methylation-specific polymerase chain reaction (qMSP-PCR) was used to analyze the DNA methylation level. The plasma homocysteine (Hcy) concentration was much higher in ischemic cases than in controls (p = 0.009), while the high-density lipoprotein (HDL) levels in stroke cases were considerably lower than in controls (p = 0.005). A significantly higher level of SHMT1 methylation was observed in the ischemic strokes (58.82 ± 17.83%) compared to that in the controls (42.59 ± 20.76%, p < 0.001). The SHMT1 methylation level was strongly correlated with HDL concentration in the healthy controls (r = 0.517, p < 0.001), while the high plasma level of Hcy showed strong association with SHMT1 methylation in ischemic strokes (r = 0.346, p < 0.001). Receiver operating characteristic (ROC) analysis of curve indicated that SHMT1 methylation has been an acceptable indicator for ischemic stroke in female patients [all sexes, area under the curve (AUC) = 0.71, p < 0.001; male patients AUC = 0.62, p = 0.032; and female patients AUC = 0.79, p < 0.001] and in all ages (AUC = 0.71, p < 0.001). In our samples, DNA methylation levels of the STHMI gene were significantly correlated with ischemic stroke in Han Chinese. STHMI hypermethylation was significantly associated with the high Hcy concentration in ischemic stroke and had value as a potential indicator for female ischemic stroke.


Relationships between anopheline mosquitoes and topography in West Timor and Java, Indonesia.
Malaria is a serious health issue in Indonesia. Mosquito control is one aspect of an integrated malaria management programme. To focus resources on priority areas, information is needed about the vectors and their habitats. This research aimed to identify the relationship between anopheline mosquitoes and topography in West Timor and Java. Study areas were selected in three topographic types in West Timor and Java. These were: coastal plain, hilly (rice field) and highland. Adult mosquitoes were captured landing on humans identified to species level and counted. Eleven species were recorded, four of which were significant for malaria transmission: Anopheles aconitus, Anopheles barbirostris, Anopheles subpictus and Anopheles sundaicus. Each species occupied different topographies, but only five were significantly associated: Anopheles annularis, Anopheles vagus and Anopheles subpictus (Java only) with hilly rice fields; Anopheles barbirostris, Anopheles maculatus and Anopheles subpictus (West Timor only) with coastal areas. Information on significant malaria vectors associated with specific topography is useful for planning the mosquito control aspect of malaria management.


The Neurobiology of Love.
Love is a complex neurobiological phenomenon, relying on trust, belief, pleasure and reward activities within the brain, i.e., limbic processes. These processes critically involve oxytocin, vasopressin, dopamine, and serotonergic signaling. Moreover, endorphin and endogenous morphinergic mechanisms, coupled to nitric oxide autoregulatory pathways, play a role. Naturally rewarding or pleasurable activities are necessary for survival and appetitive motivation, usually governing beneficial biological behaviors like eating, sex, and reproduction. Yet, a broad basis of common signaling and beneficial neurobiological features exists with connection to the love concept, thereby combining physiological aspects related to maternal, romantic or sexual love and attachment with other healthy activities or neurobiological states. Medical practice can make use of this concept, i.e., mind/body or integrative medicine. Thus, love, pleasure, and lust have a stress-reducing and health-promoting potential, since they carry the ability to heal or facilitate beneficial motivation and behavior. In addition, love and pleasure ensure the survival of individuals and their species. After all, love is a joyful and useful activity that encompasses wellness and feelings of well-being.


Downregulation of TRAIL-Receptor 1 Increases TGFβ Type II Receptor Expression and TGFβ Signalling Via MicroRNA-370-3p in Pancreatic Cancer Cells.
The accumulation of perturbations in signalling pathways resulting in an apoptosis-insensitive phenotype is largely responsible for the desperate prognosis of patients with pancreatic ductal adenocarcinoma (PDAC). Accumulating evidence suggests that the death receptors TRAIL-R1 and TRAIL-R2 play important roles in PDAC biology by acting as either tumour suppressors through induction of cell death or tumour promoters through induction of pro-inflammatory signalling, invasion and metastasis. TRAIL-R2 can also associate with nuclear proteins and alter the maturation of micro RNAs (miRs). By genome-wide miR profiling and quantitative PCR analyses we now demonstrate that knockdown of TRAIL-R1 in PDAC cells decreased the level of mature miR-370 and led to an increased abundance of the type II receptor for transforming growth factor β (TGFβ). Transfection of cells with an artificial miR-370-3p decreased the levels of TGFβ-RII. We further show that transient expression of the miR-370 mimic decreased TGFβ1-induced expression of SERPINE1 encoding plasminogen activator-inhibitor 1 and partially relieved TGFβ1-induced growth inhibition. Moreover, stable TRAIL-R1 knockdown in Colo357 cells increased TGFβ1-induced SERPINE1 expression and this effect was partially reversed by transient expression of the miR-370 mimic. Finally, after transient knockdown of TRAIL-R1 in Panc1 cells there was a tendency towards enhanced activation of Smad2 and JNK1/2 signalling by exogenous TGFβ1. Taken together, our study reveals that TRAIL-R1 through regulation of miR-370 can decrease the sensitivity of PDAC cells to TGFβ and therefore represents a potential tumour suppressor in late-stage PDAC.


Drug screening identifies niclosamide as an inhibitor of breast cancer stem-like cells.
The primary cause of death from breast cancer is the progressive growth of tumors and resistance to conventional therapies. It is currently believed that recurrent cancer is repopulated according to a recently proposed cancer stem cell hypothesis. New therapeutic strategies that specifically target cancer stem-like cells may represent a new avenue of cancer therapy. We aimed to discover novel compounds that target breast cancer stem-like cells. We used a dye-exclusion method to isolate side population (SP) cancer cells and, subsequently, subjected these SP cells to a sphere formation assay to generate SP spheres (SPS) from breast cancer cell lines. Surface markers, stemness genes, and tumorigenicity were used to test stem properties. We performed a high-throughput drug screening using these SPS. The effects of candidate compounds were assessed in vitro and in vivo. We successfully generated breast cancer SPS with stem-like properties. These SPS were enriched for CD44(high) (2.8-fold) and CD24(low) (4-fold) cells. OCT4 and ABCG2 were overexpressed in SPS. Moreover, SPS grew tumors at a density of 10(3), whereas an equivalent number of parental cells did not initiate tumor formation. A clinically approved drug, niclosamide, was identified from the LOPAC chemical library of 1,258 compounds. Niclosamide downregulated stem pathways, inhibited the formation of spheroids, and induced apoptosis in breast cancer SPS. Animal studies also confirmed this therapeutic effect. The results of this proof-of-principle study may facilitate the development of new breast cancer therapies in the near future. The extension of niclosamide clinical trials is warranted.


Tight control of STAT5 activity determines human CD34-derived interstitial dendritic cell and langerhans cell development.
Despite the crucial function of dendritic cells (DC) in immunity, the molecular mechanisms regulating human DC development remain poorly defined. STAT5 regulates various hematopoietic lineages and is activated by GM-CSF, a critical cytokine in DC development. In this study, we investigated the role of STAT5 during differentiation of human CD34(+) hematopoietic progenitors into precursor DC (pre-DC) and their subsequent differentiation toward interstitial DC and Langerhans cells. Inhibiting STAT5 activity by dominant-negative STAT5 promoted Langerhans cell commitment of hematopoietic progenitors but resulted in loss of pre-interstitial DC development, showing subset-specific regulation. Increasing the low endogenous STAT5 activity by ectopic STAT5 activation downregulated expression of the critical DC transcription factor PU.1 and abrogated commitment to either DC lineage. In contrast, high STAT5 activity was beneficial in already committed pre-DC: terminal DC differentiation was associated with increased endogenous STAT5 phosphorylation levels, JAK2-STAT5 inhibition reduced terminal DC differentiation, and conditional STAT5 activation in pre-DC improved development of BDCA-1(+), DC-SIGN(+), and Langerin(+) DC with normal maturation and T cell stimulation. These data show that STAT5 critically regulates human DC development, with specific requirements for the level of STAT5 activation at distinct differentiation stages. By regulating STAT5 activity, cytokines present at specific locations and under different pathophysiological conditions can determine the fate of DC precursors.


Intracellular Cytokine Staining and Flow Cytometry: Considerations for Application in Clinical Trials of Novel Tuberculosis Vaccines.
Intracellular cytokine staining combined with flow cytometry is one of a number of assays designed to assess T-cell immune responses. It has the specific advantage of enabling the simultaneous assessment of multiple phenotypic, differentiation and functional parameters pertaining to responding T-cells, most notably, the expression of multiple effector cytokines. These attributes make the technique particularly suitable for the assessment of T-cell immune responses induced by novel tuberculosis vaccines in clinical trials. However, depending upon the particular nature of a given vaccine and trial setting, there are approaches that may be taken at different stages of the assay that are more suitable than other alternatives. In this paper, the Tuberculosis Vaccine Initiative (TBVI) TB Biomarker Working group reports on efforts to assess the conditions that will determine when particular assay approaches should be employed. We have found that choices relating to the use of fresh whole blood or peripheral blood mononuclear cells (PBMC) and frozen PBMC; use of serum-containing or serum-free medium; length of stimulation period and use of co-stimulatory antibodies can all affect the sensitivity of intracellular cytokine assays. In the case of sample material, frozen PBMC, despite some loss of sensitivity, may be more advantageous for batch analysis. We also recommend that for multi-site studies, common antibody panels, gating strategies and analysis approaches should be employed for better comparability.


Theory! The missing link in understanding the performance of neonate/infant home-visiting programs to prevent child maltreatment: a systematic review.
Home-visiting programs have been offered for more than sixty years to at-risk families of newborns and infants. But despite decades of experience with program delivery, more than sixty published controlled trials, and more than thirty published literature reviews, there is still uncertainty surrounding the performance of these programs. Our particular interest was the performance of home visiting in reducing child maltreatment. We developed a program logic framework to assist in understanding the neonate/infant home-visiting literature, identified through a systematic literature review. We tested whether success could be explained by the logic model using descriptive synthesis and statistical analysis. Having a stated objective of reducing child maltreatment-a theory or mechanism of change underpinning the home-visiting program consistent with the target population and their needs and program components that can deliver against the nominated theory of change-considerably increased the chance of success. We found that only seven of fifty-three programs demonstrated such consistency, all of which had a statistically significant positive outcome, whereas of the fifteen that had no match, none was successful. Programs with a partial match had an intermediate success rate. The relationship between program success and full, partial or no match was statistically significant. Employing a theory-driven approach provides a new way of understanding the disparate performance of neonate/infant home-visiting programs. Employing a similar theory-driven approach could also prove useful in the review of other programs that embody a diverse set of characteristics and may apply to diverse populations and settings. A program logic framework provides a rigorous approach to deriving policy-relevant meaning from effectiveness evidence of complex programs. For neonate/infant home-visiting programs, it means that in developing these programs, attention to consistency of objectives, theory of change, target population, and program components is critical.


Sucrose supplementation suppressed the growth inhibition in polyhydroxyalkanoate-producing plants.
Polyhydroxyalkanoate (PHA) is a thermoplastic polymer with several advantageous properties, including biomass origin, biocompatibility, and biodegradability. PHA is synthesized in transgenic plants harboring 3 enzymatic genes: phaA, phaB, and phaC (collectively referred to as phaABC). PHA-producing plants exhibit severe growth inhibition that leads to extremely low PHA accumulation when these enzymes are localized in the cytosol. This growth inhibition could be attributed to the deleterious effects of the PHA biosynthetic pathway on endogenous essential metabolites or to PHA cytotoxicity itself. We performed precise morphological observations of phaABC-overexpressing Arabidopsis (ABC-ox), which displayed typical growth inhibition. On growth medium without sucrose, ABC-ox exhibited a pale green phenotype, dwarfism, including small cotyledons and true leaves, and short roots. ABC-ox partially recovered from this growth inhibition when the growth medium was supplemented with 1% sucrose. This recovery was reversed after ABC-ox grown on 1% sucrose medium was transferred to soil. ABC-ox grown on 1% sucrose medium not only demonstrated recovery from growth inhibition but were also the only examined plants with PHA accumulation, suggesting that growth inhibition was not caused by PHA cytotoxicity but rather by a lack of essential metabolites.


Characteristic imaging findings in lymphoceles of the head and neck.
Lymphoceles are benign neck cysts that are important to differentiate from congenital, infectious, and malignant cystic neck masses because they require unique surgical treatment and follow-up. We reviewed a series of surgically proven lymphoceles to delineate the radiologic characteristics of lymphoceles that differentiate them from other cystic neck masses. A search of radiology report impressions for the terms "lymphocele" and "lymphatic cyst" was performed on all neck CT, MRI, and sclerotherapy studies from January 2003 to December 2009 at our institution. Clinical and pathology records were searched for the same terms to identify additional cases. Medical records confirmed diagnosis. Study images were reviewed on PACS to assess cyst location and imaging characteristics. There were nine patients (six women and three men; age range, 22-85 years; mean age, 50.1 years) with 12 pathologically proven lymphoceles on six contrast-enhanced CT and three contrast-enhanced MRI examinations. Lymphoceles were located in the posterior cervical space in 12 of 12 and supraclavicular in 10 of 12 cases. Lymphoceles were unilocular nonseptated cysts in 12 of 12, fluid density or signal in 11 of 12, nonenhancing in 12 of 12, and lacked a cyst wall in eight of 12. Lymphoceles are rare unilocular cystic neck masses that may mimic other congenital, infectious, and malignant neck cysts. When enhanced CT or MRI shows a unilocular, nonseptated, fluid density or intensity, and nonenhancing supraclavicular cyst in the posterior cervical space, lymphocele is an important part of the differential diagnosis. Atypical features warrant fine-needle aspiration or follow-up for confirmation.