Risk stratification in follicular neoplasm: a cytological assessment using the modified Bethesda classification.
The 2007 Bethesda classification for thyroid cytology defines follicular neoplasm as a category of cases with cellular specimens demonstrating abundant follicular cells arranged in a microfollicular pattern with little or no colloid. The current recommendation for the management of these cases is diagnostic lobectomy. There has been great difficulty and variability in triaging and reporting follicular neoplasm. To increase diagnostic accuracy, at the study institution, this category is subclassified further into 3 categories: 1) microfollicular-patterned neoplasm (MN); 2) Hürthle cell neoplasm (HN); and 3) follicular lesion with some features suggestive of but not diagnostic of the follicular variant of papillary thyroid carcinoma (FL). The authors reviewed the cases of follicular neoplasm observed over a period of 5 years to document the follow-up trend using this modified classification. A search of the cytology records was performed for the period between January 2008 and December 2012. All thyroid fine-needle aspiration cases were reviewed and those with a diagnosis of follicular neoplasm (including Hürthle cell neoplasm) were identified. Correlating follow-up surgical pathology reports were reviewed. A total of 399 cases of follicular neoplasm with surgical follow-up were identified. Malignancy was identified in 32% of all cases of follicular neoplasm and was found to be disproportionately higher in the FL category (73%). A cytological diagnosis of FL is more likely to be called malignant (73%) than benign neoplastic (9%) or benign nonneoplastic (18%). A cytological diagnosis of MN or HN is more likely to be benign neoplastic (46% and 46%, respectively) than malignant (29% and 26%, respectively) or benign nonneoplastic (25% and 28%, respectively). Of the cytological features examined, 2 (nuclear enlargement and nuclear grooves) were significantly associated with the follicular variant of papillary thyroid carcinoma. The results of the current study clearly indicate that follicular lesions with even subtle nuclear atypia have a high positive predictive value for malignancy and therefore should be distinguished from other follicular lesions because these cases require more aggressive surgical management. The current study also raises an important issue concerning the current thyroid classification based on the 2007 Bethesda classification for thyroid cytology. Future thyroid fine-needle aspiration classification schemes should consider subclassifying follicular neoplasms for the purpose of risk stratification.


[Equity in health and health technology assessment in Chile].
Equity has been recognized as one of the driving principles of many health systems in the world. In Latin America, Chile has led the explicit inclusion of equity in their health policies, which is reflected in its recent health reform. On the other hand, Chile faces the challenge of defining and implementing a policy for health technology assessment (HTA), which should be consistent with the equity principles that underlie the Chilean national health system. This paper reviews the equity concept emphasizing the relevance of socioeconomic inequalities. Furthermore, it examines how international HTA agencies have explicitly included this element in the evaluation and decision processes. It presents the English case, which highlights the elements of procedural justice rather than adopting a normative position regarding equity. Finally, it examines the methods that have been developed aiming to make explicit consideration of equity in HTA. It concludes that the methodological development to incorporate equity elements with empirical basis is recent and limited. The consideration of equity is, in most of the cases, left to the instances of deliberative participation.


[Toxic hepatitis associated with Polygoni multiflori].
Toxic hepatitis has been reported as a major cause of acute hepatitis, but its potential induction by herbal remedies and/or health foods is usually neglected. We experienced a case of toxic hepatitis associated with Polygoni multiflori, a Chinese herb commonly known as Ho-Shou-Wu. A 54-year-old woman consumed Ho-Shou-Wu for 1 month, after which she experienced fatigue and overall weakness. A diagnosis of toxic hepatitis was made based on her clinical history, the findings for viral markers and other laboratory data, and ultrasonography. Her condition improved considerably after she stopped taking Ho-Shou-Wu. However, she resumed taking Ho-Shou-Wu immediately after discharge from hospital, which aggravated her symptoms and liver function. She was immediately readmitted and stopped taking Ho-Shou-Wu. Her relapse into hepatitis immediate after resuming consumption of the herb is strongly indicative of the validity of Koch's postulate in this case.


Staying out of the heat: how habitat use is determined by local temperature.
Atlantic cod (Gadus morhua) and the Tvedestrand fjord on the Norwegian Skagerrak coast studied by Freitas et al. (). Photographs by Øystein Paulsen (left), and Institute of Marine Research, Norway (right). In Focus: Freitas, C., Olsen, E. M., Knutsen, H., Albretsen, J. & Moland, E. (2016) Temperature-associated habitat selection in a cold-water marine fish. Journal of Animal Ecology, 85, 611-613. In the marine environment, species distributions are closely linked to temperature gradients, but how individual behaviour is affected by local temperatures is less well understood. Freitas et al. () tracked Atlantic cod within a Norwegian fjord using electronic acoustic tags. They showed that when surface waters were warm, cod occupied the cold deep non-vegetated habitats. However, when surface waters cooled, fish moved into shallow seagrass and macroalgae beds that were previously out-of-bounds. The study provides a clear example of how thermal regimes determine habitat use over fine spatial and temporal scales, with potential implications for population dynamics under climate warming.


Interfacial Microstructure Evolution Due to Strain Path Changes in Sliding Contacts.
We performed large-scale molecular dynamics (MD) simulations to study the transient softening stage that has been observed experimentally in sliding interfaces subject to strain path changes. The occurrence of this effect can be of crucial importance for the energy efficiency and wear resistance of systems that experience changes in the sliding direction, such as bearings or gears in wind parks, piston rings in combustion engines, or wheel-rail contacts for portal cranes. We therefore modeled the sliding of a rough counterbody against two polycrystalline substrates of face-centered cubic (fcc) copper and body-centered cubic (bcc) iron with initial near-surface grain sizes of 40 nm. The microstructural development of these substrates was monitored and quantified as a function of time, depth, and applied pressure during unidirectional sliding for 7 ns. The results were then compared to the case of sliding in one direction for 5 ns and reversing the sliding direction for an additional 2 ns. We observed the generation of partial dislocations, grain refinement, and rotation as well as twinning (for fcc) in the near-surface region. All microstructures were increasingly affected by these processes when maintaining the sliding direction but recovered to a great extent upon sliding reversal up to applied pressures of 0.4 GPa in the case of fcc Cu and 1.5 GPa for bcc Fe. We discuss the applicability and limits of our polycrystalline MD model for reproducing well-known bulk phenomena such as the Bauschinger effect in interfacial processes.


PromA Plasmids Are Instrumental in the Dissemination of Linuron Catabolic Genes Between Different Genera.
PromA plasmids are broad host range (BHR) plasmids, which are often cryptic and hence have an uncertain ecological role. We present three novel PromA γ plasmids which carry genes associated with degradation of the phenylurea herbicide linuron, two of which originated from unrelated Hydrogenophaga hosts isolated from different environments (pPBL-H3-2 and pBPS33-2), and one (pEN1) which was exogenously captured from an on-farm biopurification system (BPS). Hydrogenophaga sp. plasmid pBPS33-2 carries all three necessary gene clusters (hylA, dca, ccd) determining the three main steps for conversion of linuron to Krebs cycle intermediates, while pEN1 only determines the initial linuron hydrolysis step. Hydrogenophaga sp. plasmid pPBL-H3-2 exists as two variants, both containing ccd but with the hylA and dca gene modules interchanged between each other at exactly the same location. Linuron catabolic gene clusters that determine the same step were identical on all plasmids, encompassed in differently arranged constellations and characterized by the presence of multiple IS1071 elements. In all plasmids except pEN1, the insertion spot of the catabolic genes in the PromA γ plasmids was the same. Highly similar PromA plasmids carrying the linuron degrading gene cargo at the same insertion spot were previously identified in linuron degrading Variovorax sp. Interestingly, in both Hydrogenophaga populations not every PromA plasmid copy carries catabolic genes. The results indicate that PromA plasmids are important vehicles of linuron catabolic gene dissemination, rather than being cryptic and only important for the mobilization of other plasmids.


[Production of hybridomas synthesizing monoclonal antibodies to streptococcal group A polysaccharide].
Nine stable hybridomas synthetizing monoclonal antibodies to the antigenic determinants of polysaccharide A of group A streptococcus were obtained. Three monoclonal antibodies possessed precipitating properties. The formation of hybridomas was found to be influenced by the presence of immune splenocytes and the standard conditions of cell fusion. The highest yield of hybridomas was observed under the conditions ensuring the growth of cell in 80-100% of the wells. Rapid and specific screening was found to be an important stage in obtaining hybridomas.


Geographical differentiation in floral traits across the distribution range of the Patagonian oil-secreting Calceolaria polyrhiza: do pollinators matter?
The underlying evolutionary processes of pollinator-driven floral diversification are still poorly understood. According to the Grant-Stebbins model speciation begins with adaptive local differentiation in the response to spatial heterogeneity in pollinators. Although this crucial process links the micro- and macroevolution of floral adaptation, it has received little attention. In this study geographical phenotypic variation was investigated in Patagonian Calceolaria polyrhiza and its pollinators, two oil-collecting bee species that differ in body size and geographical distribution. Patterns of phenotypic variation were examined together with their relationships with pollinators and abiotic factors. Six floral and seven vegetative traits were measured in 45 populations distributed across the entire species range. Climatic and edaphic parameters were determined for 25 selected sites, 2-16 bees per site of the most frequent pollinator species were captured, and a critical flower-bee mechanical fitting trait involved in effective pollination was measured. Geographical patterns of phenotypic and environmental variation were examined using uni- and multivariate analyses. Decoupled geographical variation between corolla area and floral traits related to the mechanical fit of pollinators was explored using a Mantel test. The body length of pollinators and the floral traits related to mechanical fit were strongly correlated with each other. Geographical variation of the mechanical-fit-related traits was decoupled from variation in corolla size; the latter had a geographical pattern consistent with that of the vegetative traits and was mainly affected by climatic gradients. The results are consistent with pollinators playing a key role in shaping floral phenotype at a geographical scale and promoting the differentiation of two floral ecotypes. The relationship between the critical floral-fit-related trait and bee length remained significant even in models that included various environmental variables and an allometric predictor (corolla area). The abiotic environment also has an important role, mainly affecting floral size. Decoupled geographical variation between floral mechanical-fit-related traits and floral size would represent a strategy to maintain plant-pollinator phenotypic matching in this environmentally heterogeneous area.


The major barriers to evidence-informed conservation policy and possible solutions.
Conservation policy decisions can suffer from a lack of evidence, hindering effective decision-making. In nature conservation, studies investigating why policy is often not evidence-informed have tended to focus on Western democracies, with relatively small samples. To understand global variation and challenges better, we established a global survey aimed at identifying top barriers and solutions to the use of conservation science in policy. This obtained the views of 758 people in policy, practice, and research positions from 68 countries across six languages. Here we show that, contrary to popular belief, there is agreement between groups about how to incorporate conservation science into policy, and there is thus room for optimism. Barriers related to the low priority of conservation were considered to be important, while mainstreaming conservation was proposed as a key solution. Therefore, priorities should focus on convincing the public of the importance of conservation as an issue, which will then influence policy-makers to adopt pro-environmental long-term policies.


Eyes absent: a gene family found in several metazoan phyla.
Genes related to the Drosophila eyes absent gene were identified in vertebrates (mouse and human), mollusks (squid), and nematodes (C. elegans). Proteins encoded by these genes consist of conserved C-terminal and variable N-terminal domains. In the conserved 271-amino acid C-terminal region, Drosophila and vertebrate proteins are 65-67% identical. A vertebrate homolog of eyes absent, designated Eya2, was mapped to Chromosome (Chr) 2 in the mouse and to Chr 20q13.1 in human. Eya2 shows a dynamic pattern of expression during development. In the mouse, expression of Eya2 was first detected in 8.5-day embryos in the region of head ectoderm fated to become the forebrain. At later stages of development, Eya2 is expressed in the olfactory placode and in a variety of neural crest derivatives. In the eye, expression of Eya2 was first detected after formation of the lens vesicle. At day 17.5, the highest level of Eya2 mRNA was observed in primary lens fibers. Low levels of Eya2 expression was detected in retina, sclera, and cornea. By postnatal day 10, Eya2 was expressed in secondary lens fibers, cornea, and retina. Although Eya2 is expressed relatively late in eye development, it belongs to the growing list of factors that may be essential for eye development across metazoan phyla. Like members of the Pax-6 gene family, eyes absent gene family members were probably first involved in functions not related to vision, with recruitment for visual system formation and function occurring later.


Prevalence and Determinants of Adherence to Oral Adjuvant Endocrine Therapy among Breast Cancer Patients in Singapore.
The success of oral adjuvant endocrine therapy (OAET) is greatly influenced by patients' level of adherence to treatment. The objective of this study is to measure the prevalence and determinants of adherence to OAET among breast cancer patients in Singapore. A cross-sectional survey of patients supplemented by analysis of their prescription records was used to collect data. Adherence to OAET was assessed using the Morisky Medication Adherence Scale-4 items and evaluation of refill gaps. Univariate and multivariate analyses were done to evaluate the association between patients' characteristics and adherence to OAET. A total of 157 women who have started OAET at least 6 months before the time of interview participated in the study, of which less than half (64 patients, 40.8%) of the patients had high adherence. Univariate analysis identified patients who were 57 years or older (P = 0.027), unemployed (P = 0.027), on aromatase inhibitors (P = 0.023), on three or more concurrent medications (P = 0.001), and had one or more comorbidities (P = 0.000) to be significantly more adherent. However, only the number of comorbidities was found to be an independent predictor of adherence in a multiple logistic regression analysis (adjusted odds ratio = 2.60; 95% confidence interval = 1.208-5.593; P = 0.015). Forgetfulness was the main reason for nonadherence mentioned by 63 (67.7%) of the 93 nonadherent patients. Low level of OAET adherence was found in this study, and forgetfulness was cited as the main reason for nonadherence. Patients were generally receptive to the implementation of various strategies to assist them with their medication-taking behavior.


Manual versus automated coding of free-text self-reported medication data in the 45 and Up Study: a validation study.
Increasingly, automated methods are being used to code free-text medication data, but evidence on the validity of these methods is limited. To examine the accuracy of automated coding of previously keyed in free-text medication data compared with manual coding of original handwritten free-text responses (the 'gold standard'). A random sample of 500 participants (475 with and 25 without medication data in the free-text box) enrolled in the 45 and Up Study was selected. Manual coding involved medication experts keying in free-text responses and coding using Anatomical Therapeutic Chemical (ATC) codes (i.e. chemical substance 7-digit level; chemical subgroup 5-digit; pharmacological subgroup 4-digit; therapeutic subgroup 3-digit). Using keyed-in free-text responses entered by non-experts, the automated approach coded entries using the Australian Medicines Terminology database and assigned corresponding ATC codes. Based on manual coding, 1377 free-text entries were recorded and, of these, 1282 medications were coded to ATCs manually. The sensitivity of automated coding compared with manual coding was 79% (n = 1014) for entries coded at the exact ATC level, and 81.6% (n = 1046), 83.0% (n = 1064) and 83.8% (n = 1074) at the 5, 4 and 3-digit ATC levels, respectively. The sensitivity of automated coding for blank responses was 100% compared with manual coding. Sensitivity of automated coding was highest for prescription medications and lowest for vitamins and supplements, compared with the manual approach. Positive predictive values for automated coding were above 95% for 34 of the 38 individual prescription medications examined. Automated coding for free-text prescription medication data shows very high to excellent sensitivity and positive predictive values, indicating that automated methods can potentially be useful for large-scale, medication-related research.


An International Comparison of Nutrition Education Standards, Occupational Standards and Scopes of Practice for Personal Trainers.
Personal trainers are well placed to provide nutrition care in line with their recommended scope of practice. However, providing nutrition care beyond their recommended scope of practice has been identified as an industry risk. The International Confederation of Registers for Exercise Professionals (ICREPs) have international standards for nutrition knowledge and skills that are recommended for all fitness professionals, including personal trainers. This study investigates whether the ICREPs standards align with i) national nutrition education standards and ii) national nutrition occupational standards and scopes of practice for personal trainers within ICREPs affiliated countries. Content analysis of each standard and/or scope of practice was undertaken to extract nutrition statements. Extracted statements were matched with nutrition components of the ICREPs standards to result in a score based on the number of aligned ICREPs knowledge and skills criteria. Ten countries, with 16 organizations, were identified as being involved in the development of national education standards, occupational standards, or scopes of practice for personal trainers. The educational and occupational standards varied widely among countries and had minimal alignment with the ICREPs standards. As such, the expected role of personal trainers in providing nutrition care appeared to differ between countries. Further work is required to support personal trainers to develop a level of knowledge and skills that enables the provision of safe, consistent, and effective nutrition care.


A modified autonomous En transposon in maize (Zea mays L.) elicits a differential response of reporter alleles.
Transposable elements in maize are composed of a defined molecular structure that includes coding sequences, determiners of functionality and ordered terminal motifs that provide binding sites for transposase proteins. Alterations in these components change the phenotypic expression of unstable genes with transposon inserts. The molecular basis for the altered timing and frequency of transposition as determined by the size and number of spots on kernels or stripes on leaves has generally been described for defective inserts in genes. Most differential patterns can be ascribed to alterations in the terminal motifs of the reporter allele structure that supplies a substrate (terminal inverted repeat motifs) for transposase activity. For autonomously functioning alleles, the explanations for changes in phenotype are not so clear. In this report, an En-related element identified as F-En is described that shares with En the recognition of a specific defective element cl(mr)888104 but differs from En in that this F-En element does not recognize the canonical cl(mr) elements that are recognized by En. Evidence is provided suggesting that F-En does not recognize other En/Spm-related defective elements, some of whose sequences are known. This modified En arose from a cl-m autonomously mutating En allele.


Cytoplasmic dynein heavy chain 1b is required for flagellar assembly in Chlamydomonas.
A second cytoplasmic dynein heavy chain (cDhc) has recently been identified in several organisms, and its expression pattern is consistent with a possible role in axoneme assembly. We have used a genetic approach to ask whether cDhc1b is involved in flagellar assembly in Chlamydomonas. Using a modified PCR protocol, we recovered two cDhc sequences distinct from the axonemal Dhc sequences identified previously. cDhc1a is closely related to the major cytoplasmic Dhc, whereas cDhc1b is closely related to the minor cDhc isoform identified in sea urchins, Caenorhabditis elegans, and Tetrahymena. The Chlamydomonas cDhc1b transcript is a low-abundance mRNA whose expression is enhanced by deflagellation. To determine its role in flagellar assembly, we screened a collection of stumpy flagellar (stf) mutants generated by insertional mutagenesis and identified two strains in which portions of the cDhc1b gene have been deleted. The two mutants assemble short flagellar stumps (<1-2 micrometer) filled with aberrant microtubules, raft-like particles, and other amorphous material. The results indicate that cDhc1b is involved in the transport of components required for flagellar assembly in Chlamydomonas.


Maternal C677T MTHFR polymorphism and environmental factors are associated with cleft lip and palate in a Mexican population.
Nonsyndromic cleft lip and cleft palate (CL/P) is associated with environmental, nutritional, and genetic factors. Maternal polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene have been associated with CL/P. To determine the relationship between the risk of having a child with CL/P and maternal C677T and A1298C MTHFR polymorphisms, the intake of folate supplements, and exposure to environmental factors during the first trimester of pregnancy, a case-control study of Mexican mothers (88 case mothers and 116 control mothers) was conducted. A questionnaire was used to assess exposure to environmental factors. The C677T and A1298C polymorphisms were identified by polymerase chain reaction with restriction fragment length polymorphism. Mothers with the 677CT or 677TT genotype had a higher risk of having a child with CL/P than mothers with the 677CC genotype (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.1-5.7). An increased risk of having a child with CL/P was associated with the lack of folate supplementation during the first trimester of pregnancy (OR, 3.8; 95% CI, 1.9-7.6), and this risk was greater in the mothers with the 677TT or 677CT genotype than mothers who reported taking folate supplements and had the 677CC genotype (OR, 11.2; 95% CI, 3.3-37.5). Pesticide exposure was associated with CL/P. There was no significant association between either the A1298C variant or tobacco exposure and the risk of CL/P. These results suggest that gene-environment interactions play an important role in the development of CL/P.


Immune checkpoint inhibitor-induced inflammatory arthritis: a novel clinical entity with striking similarities to seronegative rheumatoid arthritis.
To determine the clinical and serologic similarities and differences between inflammatory arthritis induced by immune checkpoint inhibitors (IA-irAE) and rheumatoid arthritis (RA). In this retrospective cross-sectional comparative study, 20 patients with IA-irAE were age and sex matched to 40 seropositive and 40 seronegative RA patients. Electronic medical records were reviewed from diagnosis of inflammatory arthritis through May 2019. Arthritis characteristics, treatment, and relevant laboratory and serologic studies were captured. Clinically, IA-irAE differed from seropositive and seronegative RA with respect to disease duration (4.18 versus 11.59 and 13.3 months, respectively, p = 0.005 (IA-irAE vs seropositive RA), p = 0.002 (IA-irAE vs seronegative RA)), polyarticular joint involvement at presentation (75% versus 97.5% and 100%, p = 0.013, p = 0.003), absence of erosive changes (5.9% vs 43.6% and 53.8%, p = 0.005, p = 0.001), mean prednisone dose (24.7 mg versus 16.53 mg and 15.68 mg, p = 0.008, p = 0.005), and use of methotrexate (5.0% versus 85.0% and 70.0%, p < 0.0001, p < 0.0001). Serologically, IA-irAE closely resembled seronegative RA. ANA positivity was seen in a minority of patients and did not differ significantly between all groups; however, the ANA staining pattern (speckled) was similar between IA-irAE and seronegative RA (100% versus 75%, respectively) and was not commonly observed in seropositive RA (18.2%). IA-irAE is a new subset of IA that resembles seronegative RA immunologically. Our findings suggest that further study of IA-irAE might provide a window into underlying pathogenic mechanisms of early-stage seronegative RA. Key Points • Comprehensive comparison of clinical features between inflammatory arthritis irAE (IA-irAE) and regular rheumatoid arthritis indicates IA-irAE as a new subset of inflammatory arthritis. • IA-irAE resembles seronegative RA immunologically, suggesting that study of IA-irAE may provide a window into underlying pathogenic mechanisms of early-stage seronegative RA.


Association of New-Onset Diabetes Mellitus in Older People and Mortality in Taiwan: A 10-Year Nationwide Population-Based Study.
Older patients with diabetes mellitus are at a higher risk of developing diabetic macro- and micro-vascular complications and cardiovascular diseases than younger diabetes mellitus patients. However, older diabetes mellitus patients are very heterogeneous in their clinical characteristics, diabetes mellitus-related complications and age at disease onset. This study aimed to evaluate the all-cause mortality rates and adverse health outcomes among older adults with new-onset diabetes mellitus through a nationwide population-based study. A retrospective cohort study. 2001-2011 data of the National Health Insurance database. Nationally representative sample of Taiwanese adults aged 65 years and older with propensity score-matched controls. All-cause mortality and adverse health outcomes. During the study period, 45.3% of patients in the diabetes mellitus cohort and 38.8% in the non-diabetes mellitus cohort died. The adjusted relative risk for mortality in the diabetes mellitus cohort compared to the non-diabetes mellitus cohort was 1.23 (95% Confidence Interval [CI]=1.16-1.30) for males and 1.27 (95%CI=1.19-1.35) for females. During the follow-up period, 8.9% of the diabetes mellitus cohort and 5.8% of the non-diabetes mellitus cohort developed cardiovascular diseases; the diabetes mellitus cohort had an adjusted relative risk of cardiovascular complications compared to the non-diabetes mellitus cohort of 1.54 (95%CI=1.36-1.75) for men and 1.70 (95%CI=1.43-2.02) for women. The adjusted relative risk of mortality in the patients with hypoglycemia compared to non-hypoglycemia patients in the diabetes mellitus cohort was 2.33 (95%CI=1.81-3.01) for men and 2.73 (95%CI=2.10-3.52) for women after adjustment for age, Charlson comorbidity index, acute coronary syndrome, respiratory disease, cancer, infectious disease and nervous system disease at baseline. New-onset diabetes in older adults is associated with an increased risk of mortality, and hypoglycemia is an important marker of this association. Individualized care plans stratified by age at onset, duration of disease, comorbidity and functional status, as well as hypoglycemia avoidance, would benefit the management of diabetes in older adults.


Dextran-conjugated anti-Ig antibodies as a model for T cell-independent type 2 antigen-mediated stimulation of Ig secretion in vitro. I. Lymphokine dependence.
We have previously demonstrated that dextran-conjugated anti-IgD antibodies (anti-delta-dex) stimulate high levels of B cell proliferation at concentrations that are 1000-fold lower than that required by unconjugated anti-Ig. We now show that anti-delta-dex may provide a suitable model to study Ig secretion stimulated by soluble T cell-independent type 2 Ag exemplified by TNP-Ficoll. Thus, both TNP-Ficoll and anti-delta-dex stimulate low to undetectable levels of Ig secretion when cultured with resting B cells. Addition of IL-5 or IL-2 stimulated enhanced anti-TNP responses in the presence of TNP-Ficoll, or induced polyclonal Ig secretion in the presence of anti-delta-dex. Both TNP-Ficoll and anti-delta-dex conjugates stimulated Ig production by Percoll-separated low density (partially activated) B cells in the absence of added lymphokines. These findings point to the similarities in the activation requirements of TNP-Ficoll and anti-delta-dex and suggest that dextran-anti-Ig conjugates, which can induce B cell activation irrespective of Ag specificity, may provide a useful model for studying various parameters that characterize the responses to soluble TI type 2 Ag.


Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database.
To investigate the risk of incident myocardial infarction, congestive heart failure, and all cause mortality associated with prescription of oral antidiabetes drugs. Retrospective cohort study. UK general practice research database, 1990-2005. 91,521 people with diabetes. Incident myocardial infarction, congestive heart failure, and all cause mortality. Person time intervals for drug treatment were categorised by drug class, excluding non-drug intervals and intervals for insulin. 3588 incident cases of myocardial infarction, 6900 of congestive heart failure, and 18,548 deaths occurred. Compared with metformin, monotherapy with first or second generation sulphonylureas was associated with a significant 24% to 61% excess risk for all cause mortality (P<0.001) and second generation sulphonylureas with an 18% to 30% excess risk for congestive heart failure (P=0.01 and P<0.001). The thiazolidinediones were not associated with risk of myocardial infarction; pioglitazone was associated with a significant 31% to 39% lower risk of all cause mortality (P=0.02 to P<0.001) compared with metformin. Among the thiazolidinediones, rosiglitazone was associated with a 34% to 41% higher risk of all cause mortality (P=0.14 to P=0.01) compared with pioglitazone. A large number of potential confounders were accounted for in the study; however, the possibility of residual confounding or confounding by indication (differences in prognostic factors between drug groups) cannot be excluded. Our findings suggest a relatively unfavourable risk profile of sulphonylureas compared with metformin for all outcomes examined. Pioglitazone was associated with reduced all cause mortality compared with metformin. Pioglitazone also had a favourable risk profile compared with rosiglitazone; although this requires replication in other studies, it may have implications for prescribing within this class of drugs.


Medical treatment of the subfertile male.
Specific and effective medical treatment is available for some subfertile males. Reproductive physiology should be reviewed with all patients and exposure to drugs and toxins known to impair testicular or accessory sex gland function should be terminated. Appropriate treatment of retrograde ejaculation, chronic infections of the genital tract, or gonadotropin deficiency is indicated. Accurate diagnosis and treatment of the impotent patient may restore potency and fertility. Pregnancies have been achieved in association with each of the empirical regimens; however, we believe that each must be viewed as experimental at this time, since results may be no better than those observed in the absence of treatment. It is our experience that patients with elevated serum levels of FSH, peritubular fibrosis, and hyalinization are unlikely to achieve fertility regardless of treatment; however, there are exceptions. As our knowledge of basic reproductive biology and clinical pathology increases, it is hoped that better guidelines and more rational and effective medical treatment for the subfertile male will evolve.


A clinical and experimental study of platelet function in chronic renal failure.
Coagulation and platelet function studies were performed on 24 normal subjects and 29 patients with chronic renal failure due to various causes. Thrombocytopenia was uncommon in the uraemic patients but there was reduced platelet retention in glass bead columns and platelet aggregation with adenosine diphosphate (ADP) and thrombin was slower and less complete than normal. The rate of platelet disaggregation in uraemic patients was significantly reduced. The abnormalities tended to be more severe in more uraemic subjects. In normal subjects no inter-relationships were observed between the various measurements of platelet activity. In patients there were significant interrelationships between the measurements of platelet aggregation with ADP and thrombin and between the measurements of aggregation and retention in glass bead columns. It is suggested that if a common pathway is involved in these reactions it is adversely affected in uraemia. Plasma coagulation defects were uncommon and present in only five of the uraemic subjects. Impaired prothrombin consumption apparently due to defective platelet function was present in half the patients but was not detected by a kaolin activation method. Although platelet coagulation function was activated during ADP aggregation and disaggregation in normal and uraemic subjects, it did not correlate in the latter with impairment of aggregation. It is suggested that aggregation and activation of platelet coagulant activity are not necessarily related aspects of platelet function. An effect of uraemic plasma on normal platelets was demonstrated by mixing experiments consistent with a humoral cause for the uraemic platelet defects.


Attitudes towards disability expressed by spouses of stroke patients.
A report is given on attitudes to disability expressed by spouses of patients disabled by cerebrovascular accident. In a sample of 79 spouses overprotection and unrealistic attitudes were a more common response than rejection or retributive guilt feelings. Attitudes of retributive guilt, rejection, unrealistic aims and overprotection in the spouse were not significantly related to the presence or absence of aphasia.


Sex-related Differences in Inflammatory Bowel Diseases: The Potential Role of Sex Hormones.
Inflammatory bowel disease (IBD), characterized by chronic inflammation of the gastrointestinal tract, is a global health care problem. Compelling evidence shows sex differences regarding the prevalence, pathophysiology, clinical presentation, and treatment outcome of IBD. Sex hormones, including estrogen, progesterone, and androgen, have been proposed to have a role in the pathogenesis of sexual dimorphism in IBD. Clinical and experimental data support the modulatory effects of sex hormones on various clinical characteristics of the disease, including intestinal barrier dysfunction and mucosal immune activation. Additionally, the potential role of sex hormones in the modulation of gut microbiota is attracting increasing attention. Here, we discuss the sex dimorphic disease profile and address the potential mechanisms involved in the sex-specific pathogenesis of IBD. Improved understanding of these sex differences in the clinic could improve the knowledge of patients with IBD with heterogeneous disease profiles.


Cloning and comparative analyses of the zebrafish Ugt repertoire reveal its evolutionary diversity.
UDP-glucuronosyltransferases (Ugts) are a supergene family of phase II drug-metabolizing enzymes that catalyze the conjugation of numerous hydrophobic small molecules with the UDP-glucuronic acid, converting them into hydrophilic molecules. Here, we report the identification and cloning of the complete zebrafish Ugt gene repertoire. We found that the zebrafish genome contains 45 Ugt genes that can be divided into three families: Ugt1, Ugt2, and Ugt5. Both Ugt1 and Ugt2 have two unlinked clusters: a and b. The Ugt1a, Ugt1b, Ugt2a, and Ugt2b clusters each contain variable and constant regions, similar to that of the protocadherin (Pcdh), immunoglobulin (Ig), and T-cell receptor (Tcr) clusters. Cloning the full-length coding sequences confirmed that each of the variable exons is separately spliced to the set of constant exons within each zebrafish Ugt cluster. Comparative analyses showed that both a and b clusters of the zebrafish Ugt1 and Ugt2 genes have orthologs in other teleosts, suggesting that they may be resulted from the "fish-specific" whole-genome duplication event. The Ugt5 genes are a novel family of Ugt genes that exist in teleosts and amphibians. Their entire open reading frames are encoded by single large exons. The zebrafish Ugt1, Ugt2, and Ugt5 genes can generate additional transcript diversity through alternative splicing. Based on phylogenetic analyses, we propose that the ancestral tetrapod and teleost Ugt1 clusters contained multiple Ugt1 paralogs. After speciation, these ancestral Ugt1 clusters underwent lineage-specific gene loss and duplication. The ancestral vertebrate Ugt2 cluster also underwent lineage-specific duplication. The intronless Ugt5 open reading frames may be derived from retrotransposition followed by gene duplication. They have been expanded dramatically in teleosts and have become the most abundant Ugt family in these lineages. These findings have interesting implications regarding the molecular evolution of genes with diversified variable exons in vertebrates.


Effects of simulated high altitude on patients who have had radial keratotomy.
Previous studies documented diurnal myopic shifts in patients who have had radial keratotomy (RK). Recently, hyperopic shifts in these patients exposed to high altitude have been reported. A direct mechanical effect of reduced barometric pressure on surgically altered corneas has been theorized to cause this hyperopic shift. Another hypothesis implicates the effect of hypobaric hypoxia on the RK incisions. The authors examined the effect of a 6-hour exposure to decreased barometric pressure on 14 normal and 18 RK corneas. Cycloplegic refraction, keratometry, corneal pachymetry, and tonometry were performed on seven control subjects and nine patients who have had RK. Measurements were obtained over 8 hours at sea level on day 1 of the study. Measurements were repeated on day 2 which included a 6-hour exposure to 12,000 feet simulated altitude in a hypobaric chamber. Results were compared between subjects and control subjects to determine the effect of a 6-hour exposure to decreased barometric pressure. There was no statistically significant difference in refraction or keratometry readings between control subjects and subjects who have had RK. Central corneal thickness decreased in the afternoon in RK eyes compared with control eyes. There was no clinically significant difference in intraocular pressure between subjects who have had RK and control subjects. A measurable hyperopic shift in RK corneas exposed to high altitude requires more than 6 hours to develop. A direct effect on corneal shape due to barometric pressure alone should produce a sudden change in refractive error. This study supports the hypothesis that a slow metabolic process is responsible for the previously documented hyperopic shifts induced by altitude. However, a barometric pressure effect requiring more than 6 hours to occur cannot be ruled out with the methodology used in this study.


Genetic control of the immune response. The effect of thymectomy on the primary and secondary antibody response of mice to poly-L(tyr, glu)-poly-D, L-ala--poly-L-lys.
The effect of thymectomy on the genetically controlled murine immune response-1 (Ir-1) to the synthetic polypeptide poly-L(Tyr, Glu)-poly-D, L-Ala--poly-L-Lys [(T, G)-A--L] was studied with both aqueous and adjuvant immunization regimens. Adult thymectomy (combined with irradiation and bone marrow transfusion) did not affect the aqueous antigen-induced (IgM) primary response of either high or low responder mice, but did ablate the (IgG) secondary or tertiary response, a response which is restricted to the high responder strains. Adult thymectomy also blocked the normal high response to (T,G)-A--L in Freund's adjuvant in high responder mice and the high response to methylated bovine serum albumin (MBSA)-(T,G)-A--L in low responder mice. Neonatal thymectomy was also effective in blocking the response to (T, G)-A--L in Freund's adjuvant in high responder mice. These data are consistent with the concept that the Ir-1 gene effect is mediated via thymus cell interaction with antigen and with "B"-cells during the time of induction of IgG antibody formation.


Pancreatic stent placement for duct disruption.
The aim of this study was to identify predictors of outcome after pancreatic duct stent placement for duct disruption. Patients were identified from endoscopy databases. Disruption was defined by extravasation of contrast from the pancreatic duct during endoscopic retrograde pancreatography. Data collected included demographic information, imaging studies, management before and outcome after stent placement. Success was defined as resolution of the disruption clinically, on radiologic imaging, and/or at endoscopic retrograde pancreatography. Forty-three patients (23 women, 20 men; mean age 57 years, [SD] 15.2 years) were studied. The etiology of pancreatic duct disruption was acute pancreatitis in 24, chronic pancreatitis in 9, operative injury in 7, and trauma in 3 patients. In 25 patients there was resolution of the disruption, whereas stent therapy was unsuccessful in 16 and the outcome was indeterminate in 2 patients. On univariate analysis, stent positioned to bridge the disruption (p = 0.04) and longer duration of stent therapy (p = 0.002) were associated with a successful outcome. Female gender (p = 0.05) and acute pancreatitis (p = 0.05) were associated with a lack of success. On multivariate analysis, only the bridging stent position remained correlated to outcome. Complications occurred in 4 patients. A bridging stent is associated with a successful outcome after pancreatic duct stent placement for duct disruption.


Edward H. Angle and the motives behind his school of orthodontia.
Despite the century that has passed since Dr. Edward Hartley Angle (1855-1930) launched a new dental specialty, his personal vision of why he believed orthodontics needed to separate from dentistry has remained somewhat obscure. This study seeks to provide more clarity to this question. Angle followed a very distinct pattern of secession or separation throughout his life, a pattern which ended up benefitting the orthodontic specialty's elevation as an independent and advanced science within dentistry. Even so, it was ultimately those things he disliked about the academic community, the very community within which dentistry flourished, that finally moved him to force the issue by separating himself from that community. The separation of orthodontics from dentistry provided a singular environment in which orthodontics could bear fruit that the average patient could benefit from, thus providing the groundwork for accelerated orthodontic developments.


Prognostic value of non-sustained ventricular tachycardia and the potential role of amiodarone treatment in hypertrophic cardiomyopathy: assessment in an unselected non-referral based patient population.
Amiodarone has been reported to reduce the likelihood of sudden death in patients with hypertrophic cardiomyopathy (HCM). However, data regarding the clinical course in HCM have traditionally come from selected referral populations biased toward assessment of high risk patients. To evaluate antiarrhythmic treatment for sudden death in an HCM population not subject to tertiary referral bias, closely resembling the true disease state present in the community. Cardiovascular mortality was assessed in relation to the occurrence of non-sustained ventricular tachycardia (NSVT) on 24 or 48 hour ambulatory Holter recording, a finding previously regarded as a marker for sudden death, particularly when the arrhythmia was frequent, repetitive or prolonged. 167 consecutive patients were analysed by multiple Holter ECG recordings (mean (SD) 157 (129) hours) and followed for a mean of 10 (5) years. Only patients with multiple repetitive NSVT were treated with amiodarone, and in relatively low. doses (220 (44) mg/day). Nine HCM related deaths occurred: 8 were the consequence of congestive heart failure, but only 1 was sudden and unexpected. Three groups of patients were segregated based on their NSVT profile: group 1 (n = 39), multiple (> or = 2 runs) and repetitive bursts (on > or = 2 Holters) of NSVT, or prolonged runs of ventricular tachycardia, included 4 deaths due to heart failure; group 2 (n = 38), isolated infrequent bursts of NSVT, included 1 sudden death; group 3 (n = 90), without NSVT, included 4 heart failure deaths. Kaplan-Meier survival analysis showed no significant differences in survival between the three groups throughout follow up. In an unselected patient population with HCM, isolated, non-repetitive bursts of NSVT were not associated with adverse prognosis and so this arrhythmia does not appear to justify chronic antiarrhythmic treatment. Amiodarone, administered in relatively low doses, did not carry an independent and additive risk for cardiac mortality. Amiodarone may have contributed to the absence of sudden cardiac death in patients believed to be at higher risk because of multiple repetitive NSVT.


Antifungal activity, toxicity and chemical composition of the essential oil of Coriandrum sativum L. fruits.
The aims of this study were to test the antifungal activity, toxicity and chemical composition of essential oil from C. sativum L. fruits. The essential oil, obtained by hydro-distillation, was analyzed by gas chromatography/mass spectroscopy. Linalool was the main constituent (58.22%). The oil was considered bioactive, showing an LC₅₀ value of 23 μg/mL in the Artemia salina lethality test. The antifungal activity was evaluated against Microsporum canis and Candida spp. by the agar-well diffusion method and the minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC) were established by the broth microdilution method. The essential oil induced growth inhibition zones of 28 ± 5.42 and 9.25 ± 0.5 for M. canis and Candida spp. respectively. The MICs and MFCs for M. canis strains ranged from 78 to 620 and 150 to 1,250 μg/mL, and the MICs and MFCs for Candida spp strains ranged from 310 to 620 and 620 to 1,250 μg/mL, respectively. C. sativum essential oil is active in vitro against M. canis and Candida spp. demonstrating good antifungal activity.


Task difficulty in mental arithmetic affects microsaccadic rates and magnitudes.
Microsaccades are involuntary, small-magnitude saccadic eye movements that occur during attempted visual fixation. Recent research has found that attention can modulate microsaccade dynamics, but few studies have addressed the effects of task difficulty on microsaccade parameters, and those have obtained contradictory results. Further, no study to date has investigated the influence of task difficulty on microsaccade production during the performance of non-visual tasks. Thus, the effects of task difficulty on microsaccades, isolated from sensory modality, remain unclear. Here we investigated the effects of task difficulty on microsaccades during the performance of a non-visual, mental arithmetic task with two levels of complexity. We found that microsaccade rates decreased and microsaccade magnitudes increased with increased task difficulty. We propose that changes in microsaccade rates and magnitudes with task difficulty are mediated by the effects of varying attentional inputs on the rostral superior colliculus activity map.


Gingiva thickening with a porcine collagen matrix in a preclinical dog model: Histological outcomes.
To compare 10-month histological and immunohistological outcomes after soft tissue thickening around teeth with a porcine collagen matrix (CM) versus a subepithelial connective tissue graft (SCTG). In eight beagle dogs, soft tissue thickening of the buccal gingiva of upper canines was performed with the SCTG or the CM. Connective tissue thickness (CTT) was histomorphometrically measured in the augmented regions. The augmented connective tissues were also histologically characterized and the collagen I and vascular endothelial growth factor (VEGF) expressions immunohistologically quantified. CTT significantly differed between groups (SCTG: 1.32 mm ± 0.44 mm; CM: 1.06 mm ± 0.27 mm; p = .008). Descriptive histological analyses revealed mature connective tissue that did not differ between groups. Immunohistological quantification of collagen I and VEGF expressions in the connective tissue also revealed no significant inter-group differences (collagen I: SCTG, 32.64% ± 7.09% vs. CM, 30.57% ± 7.83%; VEGF: SCTG, 39.06% ± 7.27% vs. CM, 37.15% ± 9.80%). SCTG is superior to CM with regard to CTT in this experimental model. The CM and the SCTG lead to comparable connective tissue quality ten months after connective tissue thickening.


The Impact of a Bayesian Penalized Likelihood Reconstruction Algorithm on the Evaluation of Indeterminate Pulmonary Nodules by Dual-Time Point 18F-FDG PET/CT.
We present the case of a patient with history of colon cancer, referred for the evaluation of indeterminate pulmonary nodules by F-FDG PET/CT. A dual-time point protocol was performed, and images were reconstructed using VUE Point HD and a Bayesian-penalized likelihood reconstruction algorithm (Q.Clear). Visually, the quality of the images was considered better when Q.Clear was used with β value of 200, uptake in the smallest nodule (7 mm) was clearly visible only with Q.Clear reconstruction, and uptake in the smaller nodules was best defined in the delayed time point acquisition. Quantitative parameters were also higher for Q.Clear.


A comparative MudPIT analysis identifies different expression profiles in heart compartments.
Cardiomyopathies indistinctly affect atrial and ventricular cardiac compartments with alterations of their mechanical and/or electrical activity. To understand the main mechanisms involved in these pathological alterations, a detailed knowledge of the physiology of the healthy heart is critical. In the present work, we utilize multidimensional protein identification technology to characterize the murine left ventricle (LV), right ventricle (RV), and atria (A) proteomes, identifying thousands of distinct proteins. Moreover, using multidimensional algorithm protein map tool, relative abundances of proteins among the heart chambers were investigated. In sum, we found 16 and 55 proteins were more abundant in LV compared to RV and A, respectively; 47 and 60 proteins were more abundant in RV than LV and A, respectively; and, 81 and 74 proteins were more abundant in A than LV and RV, respectively. This detailed characterization of myocardial compartment proteome represents an important advancement in the knowledge of heart physiology, and may contribute to the identification of key features underlying the onset of cardiomyopathy.


An ultrafiltration technique for directly reinfusing residual cardiopulmonary bypass blood.
Given the shortages of banked blood, the risks of transfusion reactions, disease transmissions, and transfusion errors, we perfusionists must find ways to avoid blood transfusions. At the end of any given bypass run, there is residual blood left in the bypass circuit, the perfusionist must get this blood back to the patient. Most commonly either a cell saver or a hemoconcentrator (HC) has been used, in some fashion, to reinfuse residual circuit blood. The ideal method should: 1) be simple; 2) raise the hematocrit (HCT); 3) allow for changes in the patient's volume status; and 4) not compromise the integrity of the cardiopulmonary bypass (CPB) circuit allowing for rapid re-institution of CPB. We describe a technique in which residual CPB circuit blood is pumped through an HC directly to the patient via a 3/16-inch diameter line into a 16-gauge intravenous needle positioned in a peripheral or central vein. This allows the perfusionist to give back concentrated blood that is protein-rich while maintaining the above criteria.


Glycine N-methyltransferase is an example of functional diversity. Role as a polycyclic aromatic hydrocarbon-binding receptor.
The cytochrome P-4501A1 (CYP1A1) gene is regulated by several trans-acting factors including the 4 S polycyclic aromatic hydrocarbon (PAH)-binding protein, which has recently been identified as glycine N-methyltransferase (GNMT) (Raha, A., Wagner, C., Macdonald, R. G., and Bresnick, E. (1994) J. Biol. Chem. 269, 5750-5756). The role of GNMT as a 4 S PAH-binding protein in mediating the induction of cytochrome P-4501A1 has been investigated further. GNMT cDNA, which was cloned into a pMAMneo vector containing the Rous sarcoma virus promoter and the neomycin resistance gene, was stably transfected into D422 Chinese hamster ovary (CHO) cells. Several positive clones were selected by reverse transcription-polymerase chain reaction and assayed for the expression of recombinant protein. Western blot analysis indicated the expression of significant levels of the 4 S protein in the stably transfected CHO cells (CHO-GNMT). Cytosolic preparations from the CHO-GNMT showed high benzo[a]pyrene (B[a]P) binding but no 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) binding activity when compared with clones transfected with the pMAMneo vector alone (CHO-neo) or the parental CHO cells. Challanging the CHO-GNMT cells with 4 microM B[a]P resulted in elevated levels of CYP1A1 mRNA. Equally effective in inducing CYP1A1 mRNA were benzo[e]pyrene and 3-methylcholanthrene. On the other hand, TCDD did not induce CYP1A1 gene expression in these cells. B[a]P-treated CHO-GNMT, expressing the 4 S protein, also showed CYP1A1 protein by Western blotting and exhibited ethoxyresorufin-O-deethylase activity; neither the CHO-neo or parental CHO cells were positive for any of these measures. No Ah receptor message or protein was detectable in the parental CHO, CHO-neo, or CHO-GNMT cells. Furthermore, no XRE binding activity was observed in TCDD-treated cytosolic preparations or nuclear extracts from CHO-GNMT cells that were treated with TCDD. These studies unequivocally establish that GNMT is a PAH-binding protein that can mediate the induction of CYP1A1 by PAHs such as B[a]P through an Ah receptor-independent pathway.


Ultrahigh-yield synthesis of N-doped carbon nanodots that down-regulate ROS in zebrafish.
Oxidative damage induced by accumulation of excessive reactive oxygen species (ROS) could result in increased chronic inflammation and thus ageing and age-related diseases. Carbonaceous nanodrugs hold great promise for ameliorating age-related diseases, and it is necessary to develop ultrahigh-yield synthesis of such nanodrugs. To improve the synthetic yield (less than 50%) of carbon nanodots (CNDs), the general choice is to screen precursors. However, no reliable concept for improving the yield has been explored over the past few decades. We are the first to propose the concept of using carbon-carbon double bonds to boost the synthetic yield and demonstrate record breaking ultrahigh-yield (85.9%) synthesis of N-doped CNDs. When the C[double bond, length as m-dash]C content increased from 14 to 56 mmol, the synthetic yield exhibited a 3.3-fold increase. Nitrogen elements are doped as pyridinic-like N and NH2, where conjugated π-systems as electron donors and pyridinic-like structures would benefit the potential down-regulated effect for ROS. N-doped CNDs exhibit an outstanding protective effect against oxidative stress via inhibiting exogenous and endogenous ROS generation, where the ROS in zebrafish are significantly reduced by 68%. Hence the concept of carbon-carbon double bond-boosted ultrahigh-yield synthesis of N-doped CNDs provides a promising strategy to be employed for carbonaceous nanodrugs aiming at preventing and curing ageing and age-related diseases.


Evaluating spatial patterns of seasonal ozone exposure and incidence of respiratory emergency room visits in Dallas-Fort Worth.
In urban environments, environmental air pollution poses significant risks to respiratory health. Moreover, the seasonal spatial variability of the air pollutant ozone, and respiratory illness within Dallas-Fort Worth (DFW) is not well understood. We examine the relationships between spatial patterns of long-term ozone exposure and respiratory illness to better understand impacts on health outcomes. We propose that this study will establish an enhanced understanding of the spatio-temporal characteristics of ozone concentrations and respiratory emergency room visits (ERV) incidence. Air pollution data (ozone) and ERV incidence data from DFW was used to evaluate the relationships between exposures and outcomes using three steps: (1) develop a geostatistical model to produce quarterly maps of ozone exposure for the DFW area; (2) use spatial analysis techniques to identify clusters of zip codes with high or low values of ozone exposure and respiratory ERV incidence; and (3) use concentration-response curves to evaluate the relationships between respiratory ERV incidence and ozone exposure. Respiratory ERV incidence was highest in quarters 1 and 4, while ozone exposure was highest in quarters 2 and 3. Extensive statistically significant spatial clusters of ozone regions were identified. Although the maps revealed that there was no regional association between the spatial patterns of high respiratory ERV incidence and ozone exposure, the concentration-response analysis suggests that lower levels of ozone exposure may still contribute to adverse respiratory outcomes.


A Novel Mutation in the Stalk Domain of KIF5A Causes a Slowly Progressive Atypical Motor Syndrome.
KIF5A encodes the heavy chain A of kinesin; A motor protein involved in motility functions within neuron. Mutations in the KIF5A N-terminal motor domain are known to cause SPG10; An autosomal dominant hereditary spastic paraplegia (HSP), as well as rare Charcot-Marie-Tooth disease 2 (CMT2) cases. Recently C-terminal cargo-binding tail domain mutations have been associated with an amyotrophic lateral sclerosis (ALS) phenotype. Here we describe a subject presenting with an atypical slowly progressive motor syndrome evolving over a period of 4 years; Characterized by walking difficulties; Muscle hypotrophy mainly involving upper limbs and pyramidal signs confined to the lower limbs. Electromyography demonstrated chronic neurogenic damage and active denervation while electroneurography showed slowly worsening axonal damage. We identified the novel heterozygote variant c.2341A>G in the exon 21 of the KIF5A gene resulting in the amino acid change p.Lys781Glu. The residue Lys781 is located within the terminal region of the stalk domain and is highly evolutionary conserved. Our findings confirm that mutations in KIF5A cause ALS-like phenotypes. However, the stalk domain mutation described here appears to result in an "intermediate" slowly progressive phenotype having aspects resembling ALS as well as HSP and axonal neuropathy. We suggest that KIF5A gene should be considered as a candidate gene in all atypical progressive motor syndromes.


Abdominocervical oesophagectomy in the elderly.
Abdominocervical (transhiatal) oesophagectomy was carried out in 8 patients. Five of 6 with oesophageal cancer were elderly (aged 75-88 years), and one was 59 years old. Two patients (aged 54 and 74 years) had recurrent achalasia and megaoesophagus 30 years after cardiomyotomy. Chest complications were common, but there were no anastomotic leaks and no deaths. In 2 patients with large paraoesophageal hiatal hernias oesophagectomy had not been planned; the procedure was undertaken for an unexpected carcinoma of the cardia and an oesophageal tear. Three patients have died of recurrent cancer at 12, 17 and 21 months. The 5 survivors are swallowing satisfactorily, although one has required two dilatations of an anastomotic stricture.


Tourette syndrome research highlights from 2019.
This is the sixth yearly article in the Tourette Syndrome Research Highlights series, summarizing research from 2019 relevant to Tourette syndrome and other tic disorders. The highlights from 2020 is being drafted on the Authorea online authoring platform; readers are encouraged to add references or give feedback on our selections comments feature on this page. After the calendar year ends, this article is submitted as the annual update for the Tics collection F1000Research.


BMP-2 expression correlates with local failure in head and neck squamous cell carcinoma.
Preclinical data show that exogenous administration of recombinant human bone morphogenetic protein-2 (rhBMP-2) to human oral carcinoma cell lines increases pathogenicity using a nude mouse model. The objectives of this study are to (1) describe the characteristics of baseline protein expression of BMP-2 in head and neck squamous cell carcinomas (HNSCC) and (2) determine if BMP-2 expression level correlates with worse oncologic outcomes. Retrospective analysis of previously harvested patient samples. Academic medical center. In total, 149 patients with oral cavity, oropharynx, larynx, and hypopharynx HNSCC treated between January 1, 1997, and December 31, 2004. A tissue microarray of HNSCC was assembled and immunohistochemistry for BMP-2 performed. Staining was quantified using a standardized scoring system. Specimens were dichotomized into high or low expression level. Statistical analyses using log-rank, Wilcoxon, and Fisher exact test were performed for associations between BMP-2 protein level and clinicopathologic features and patient survival. BMP-2 expression at any level was noted in 146 of 149 (98%) of samples. Tumors with high BMP-2 expression had higher rates of local failure compared with low-expressing tumors (17.3% vs 6.3%; P = .04). There was no significant association for BMP-2 expression level with tumor location, T stage, N stage, overall survival, regional failure, or distant failure. Head and neck squamous cell carcinomas with high baseline BMP-2 protein level are associated with higher rates of local recurrence. These data have important implications for using rhBMP-2 in tissue engineering reconstructive approaches in the setting of cancer-related defects.


Vitamin D inadequacy is widespread in Tunisian active boys and is related to diet but not to adiposity or insulin resistance.
Vitamin D inadequacy is widespread in children and adolescents worldwide. The present study was undertaken to assess the vitamin D status in active children living in a sunny climate and to identify the main determinants of the serum concentration of 25-hydroxyvitamin D (25-OHD). This cross-sectional study included 225 children aged 7-15 years practicing sports in a football academy. Anthropometric measures were performed to calculate body mass index (BMI), fat mass, and maturity status. A nutritional enquiry was performed including 3-day food records and food frequency questionnaire. Plasma 25-OHD and insulin were assessed by immunoenzymatic methods ensuring categorization of vitamin D status and calculation of insulin sensitivity/resistance indexes. A logistic regression model was applied to identify predictors for vitamin D inadequacy. Vitamin D deficiency (25-OHD<12 µg/L) was observed in 40.9% of children and insufficiency (12<25-OHD<20 µg/L) was observed in 44% of children. In a multivariate analysis, vitamin D deficiency and insufficiency were associated with a lower dietary intake of vitamin D, proteins, milk, red meat, fish, and eggs. However, no significant relationship was observed with maturation status, adiposity, or insulin resistance. Tunisian children and adolescents are exposed to a high risk of vitamin D inadequacy despite living in a sunny climate. Circulating 25-OHD concentrations are related to the intake of vitamin D food sources but not to maturation status or body composition. Ensuring sufficient and safe sun exposure and adequate vitamin D intake may prevent vitamin D inadequacy in children from sunny environments.


Survival of methicillin-resistant Staphylococcus aureus during commercial heat treatment of slab bacon and consumer preparation of sliced bacon.
With the knowledge that retail pork products may be contaminated with methicillin-resistant Staphylococcus aureus (MRSA), the risk of consumers contracting a MRSA infection or foodborne illness from processed meats, especially bacon, is uncertain. Therefore, a study was designed to investigate the survival of MRSA during heat treatment of slab bacon at a commercial process and during cooking of sliced bacon at the consumer level. Fresh pork bellies were injected with a curing solution, inoculated, and heat treated to an internal temperature of 52°C. Three commercial brands of sliced bacon with similar "sell by" dates and fat-to-lean ratios were also inoculated and cooked at a temperature of 177°C for 0, 2, and 5 min on each side. Heat-treated slab bacon showed a log reduction of 1.89, which was significant (P < 0.05) compared with an uncooked inoculated control. Cooked sliced bacon had a reduction of viable MRSA cells of >6.5 log CFU/cm(2), and there was not a significant brand interaction (P > 0.05).


Quality of life among Iranian patients with beta-thalassemia major using the SF-36 questionnaire.
CONTEXT AND OBJECTIVE Patients with beta-thalassemia major (β-TM) experience physical, psychological and social problems that lead to decreased quality of life (QoL). The aim here was to measure health-related QoL and its determinants among patients with β-TM, using the Short Form-36 (SF-36) questionnaire. DESIGN AND SETTING Cross-sectional study at the Hematology Research Center of Shiraz University of Medical Sciences, in southern Iran. METHODS One hundred and one patients with β-TM were randomly selected. After the participants' demographics and disease characteristics had been recorded, they were asked to fill out the SF-36 questionnaire. The correlations of clinical and demographic factors with the QoL score were evaluated. RESULTS There were 44 men and 57 women of mean age 19.52 ± 4.3 years (range 12-38). On two scales, pain (P = 0.041) and emotional role (P = 0.009), the women showed significantly lower scores than the men. Lower income, poor compliance with iron-chelating therapy and presence of comorbidities were significantly correlated with lower SF-36 scores. These factors were also found to be determinants of worse SF-36 scores in multivariate analysis. CONCLUSIONS We showed that the presence of disease complications, poor compliance with iron-chelating therapy and poor economic status were predictors of worse QoL among patients with β-TM. Prevention and proper management of disease-related complications, increased knowledge among patients regarding the importance of managing comorbidities and greater compliance with iron-chelating therapy, along with psychosocial and financial support, could help these patients to cope better with this chronic disease state.


Childhood psychopathology in children of women with eating disorders: understanding risk mechanisms.
Very few studies have investigated psychopathology in children of mothers with eating disorders (ED). We aimed to determine the effect of maternal ED on childhood psychopathology in a large population-based cohort and investigate relevant risk pathways using structural equation modeling (SEM). Data on emotional and behavioral problems at 3½ years were obtained prospectively on 8,622 children from the Avon Longitudinal Study of Parents and Children (ALSPAC). Children of exposed women who self-reported lifetime anorexia nervosa (AN, N = 193) or bulimia nervosa (BN, N = 158) in pregnancy were compared with children of unexposed women (N = 8,271) using linear and logistic regression models. SEM was used to determine best-fitting risk models by child gender. There was evidence that girls of AN women were more likely to have emotional, conduct, and hyperactivity disorders [Odds Ratio (OR): 1.7 (95% Confidence Intervals 1.0-3.0); OR: 2.2 (1.2-4.0); OR: 1.8 (1.1-3.1), respectively] and boys of AN women to have emotional disorders compared with unexposed [OR: 2.0(1.2-3.4)]. Girls of women with BN were more likely to show hyperactivity [OR: 1.7 (1.0-3.1)]; and boys to show emotional and conduct disorders compared with unexposed [OR: 2.2 (1.2-3.9); OR: 2.4 (1.4-4.2), respectively]. SEM models showed that pregnancy anxiety and depression mediated the effect of maternal ED on child psychopathology. Maternal ED are associated with different childhood psychopathology outcomes in boys and girls. Pregnancy anxiety and depression and active ED symptoms are important mediators of risk and are preventable; the direct effect of maternal lifetime ED was small.


Mammalian alkaline phosphatase catalysis requires active site structure stabilization via the N-terminal amino acid microenvironment.
In mammalian alkaline phosphatase (AP) dimers, the N-terminus of one monomer embraces the other, stretching toward its active site. We have analyzed the role of the N-terminus and its microenvironment in determining the enzyme stability and catalysis using human placental (PLAP) and tissue-nonspecific AP (TNAP) as paradigms. Deletion of nine amino acid (aa) residues in PLAP reduced its AP activity and heat stability, while deletion of 25 aa resulted in an inactive enzyme. In turn, deletion of five and nine N-terminal aa in TNAP reduced and abolished AP activity, respectively. The N-terminal aa deletions in both isozymes affected the rate of substrate catalysis (k(cat)), with an only minor effect on the Michaelis constant (K(m)) explained by decelerated intramolecular transition rates in the active site. Arg370 in PLAP, and the corresponding Arg374 in TNAP, critically control the structure and function of the enzymes, but the Glu6-Arg370 bond predicted by the PLAP crystal structure appeared to be irrelevant with respect to PLAP stability or catalysis. Structural disruption was also noted in [R374A]TNAP, [Delta5]TNAP, [Delta9]TNAP, and [Delta25]TNAP using a panel of 19 anti-TNAP antibodies illustrating the structural role of the N-terminus. Our data reveal that the N-terminal alpha-helical folding is more crucial for the structural stability of the second monomer in TNAP than in PLAP. The correct folding of the N-terminus and of interacting loops in its immediate environment is essential for overall structural integrity and for execution of intramolecular transitions during enzyme catalysis. These findings provide a mechanistic interpretation for loss-of-function mutations of N-terminal TNAP residues in cases of hypophosphatasia.


Colorimetric discrimination between important alkaloid nuclei mediated by a bis-salphen chromophore.
A new colorimetric method is presented that allows for simple and effective discrimination between (iso)quinoline nuclei pertinent to many alkaloid species. The method is based on the reversible incorporation of Zn2+ ions into a bis-salphen chromophore under aqueous conditions. The metalation process is a function of the stability of the Zn-N (acceptor-donor) interaction and is accompanied by a clear colorimetric response.


Sparsity-Based Color Image Super Resolution via Exploiting Cross Channel Constraints.
Sparsity constrained single image super-resolution (SR) has been of much recent interest. A typical approach involves sparsely representing patches in a low-resolution (LR) input image via a dictionary of example LR patches, and then using the coefficients of this representation to generate the high-resolution (HR) output via an analogous HR dictionary. However, most existing sparse representation methods for SR focus on the luminance channel information and do not capture interactions between color channels. In this paper, we extend sparsity-based SR to multiple color channels by taking the color information into account. Edge similarities amongst RGB color bands are exploited as cross channel correlation constraints. These additional constraints lead to a new optimization problem, which is not easily solvable; however, a tractable solution is proposed to solve it efficiently. Moreover, to fully exploit the complementary information among color channels, a dictionary learning method is also proposed specifically to learn color dictionaries that encourage edge similarities. Merits of the proposed method over state of the art are demonstrated both visually and quantitatively using image quality metrics.


[Morphology and clinical aspects of malignant mixed müllerian tumors of the corpus uteri].
Mixed muellerian tumours of the uterus are more common today than uterine leiomyosarcomata. There is a world wide increase in the incidence in the last few years. In the past 15 years we observed 20 mixed muellerian tumours of the uterine body. The patients are usually 10 years older than women with endometrial carcinoma or leiomyosarcoma of the uterus. Morphologically homologous and heterologous tumours must be differentiated. Characteristic is the marked polypoid growth. There is a close correlation between tumour stage and microscopic tumour grading. Tumours with high malignancy are usually in stage I or II. The prognosis correlates well with the grade and stage of the tumour, therefore the elaboration of a prognostic index is necessary. The survival rates are low. Mixed muellerian tumours are not at all or very little influenced by radiotherapy. The single or combined chemotherapies in use o date have not shown satisfactory success. As complete as possible surgical removal is therefore important. It cannot as yet be predicted whether our present combined treatment in stage III and stage IV by operation and post-operative combined chemotherapy with CYVADIC is liable to increase the survival rates.


Implanting the glucose enzyme electrode: problems, progress, and alternative solutions.
An implantable glucose sensor is needed before a reliable artificial pancreas can be realized. The principles and current status of one such device, the glucose enzyme electrode, is presented and discussed. While monitoring glucose this enzyme sensor consumes enough oxygen to become oxygen-limited. This problem has been solved by developing hydrophobic membranes that are more permeable to oxygen than to glucose. Two types of membranes with this property made from (1) cross-linked albumin and (2) sebacyl chloride (nylon) are described. Placing these membranes over the glucose enzyme electrode solves the problem of oxygen limitation. Furthermore, the addition of this type of membrane increases the linear response range of the electrode to glucose to include the entire clinical range of interest (0-400 mg/dl). Other problems in developing an implantable glucose sensor are discussed. Competing strategies to achieve an implantable artificial pancreas without using electronic or mechanical components are presented and evaluated.


Short-segment compression instrumentation for selected thoracic and lumbar spine fractures: the short-rod/two-claw technique.
The short-rod/two-claw (SRTC) technique of spine instrumentation was recently introduced for the treatment of thoracic and lumbar spine fractures. The use of this technique in 10 patients harboring wedge compression or burst fractures of the thoracic or lumbar spine is described. Of three patients treated with the construct placed in a distraction mode, the average follow-up loss of angle (the difference between the immediate postoperative and follow-up midsagittal angle as measured on x-ray films) was 18.3 degrees. Of the seven patients in whom the instrumentation was placed in a compression mode, the average observed loss of angle at follow-up examination was 1.6 degrees. Two patients had a preoperative scoliotic deformity at the fracture site, and both deformities were exaggerated by the placement of the SRTC technique in compression. Although no patient experienced an adverse outcome and all achieved a solid fusion, the application of the SRTC technique of universal spine instrumentation in distraction was associated with an exaggerated loss of angle. Loss of angle and deformity exaggeration are not desirable and are preventable by strict patient selection and by applying the construct in a compression mode. It is emphasized that few patients are candidates for this form of instrumentation. When applicable, however, the advantages of decreased pain and stiffness and the elimination of the need for instrumentation removal make the SRTC and related short-segment techniques desirable alternatives to traditional methods of spinal fixation.


Patterns of dendritic cell and monocyte subsets are associated with disease severity and mortality in liver cirrhosis patients.
Liver cirrhosis is often complicated by an immunological imbalance known as cirrhosis-associated immune dysfunction. This study aimed to investigate disturbances in circulating monocytes and dendritic cells in patients with acute decompensation (AD) of cirrhosis. The sample included 39 adult cirrhotic patients hospitalized for AD, 29 patients with stable cirrhosis (SC), and 30 healthy controls (CTR). Flow cytometry was used to analyze monocyte and dendritic cell subsets in whole blood and quantify cytokines in plasma samples. Cirrhotic groups showed higher frequencies of intermediate monocytes (iMo) than CTR. AD patients had lower percentages of nonclassical monocytes than CTR and SC. Cirrhotic patients had a profound reduction in absolute and relative dendritic cell numbers compared with CTR and showed higher plasmacytoid/classical dendritic cell ratios. Increased plasma levels of IL-6, IL-10, and IL-17A, elevated percentages of CD62L+ monocytes, and reduced HLA-DR expression on classical monocytes (cMo) were also observed in cirrhotic patients. Patients with more advanced liver disease showed increased cMo and reduced tissue macrophages (TiMas) frequencies. It was found that cMo percentages greater than 90.0% within the monocyte compartment and iMo and TiMas percentages lower than 5.7% and 8.6%, respectively, were associated with increased 90-day mortality. Monocytes and dendritic cells are deeply altered in cirrhotic patients, and subset profiles differ between stable and advanced liver disease. High cMo and low TiMas frequencies may be useful biomarkers of disease severity and mortality in liver cirrhosis.


Maternal Western-style diet affects offspring islet composition and function in a non-human primate model of maternal over-nutrition.
In humans, offspring of women who are overweight or obese are more likely to develop metabolic disease later in life. Studies in lower animal species reveal that a calorically-dense maternal diet is associated with alterations in islet cell mass and function. The long-term effects of maternal diet on the structure and function of offspring islets with characteristics similar to humans are unknown. We used a well-established non-human primate (NHP) model to determine the consequences of exposure to Western-Style Diet (WSD) in utero and during lactation on islet cell mass and function in the offspring. Female Japanese Macaques (Macaca fuscata) were fed either control (CTR) or WSD before and throughout pregnancy and lactation. Offspring were weaned onto CTR or WSD to generate four different groups based on maternal/offspring diets: CTR/CTR, WSD/CTR, CTR/WSD, and WSD/WSD. Offspring were analyzed at three years of age. Pancreatic tissue sections were immunolabelled to measure α- and β-cell mass and proliferation as well as islet vascularization. Live islets were also isolated to test the effects of WSD-exposure on islet function ex vivo. Offspring glucose tolerance was correlated with various maternal characteristics. α-cell mass was reduced as a result of maternal WSD exposure. α-cell proliferation was reduced in response to offspring WSD. Islet vasculature did not differ among the diet groups. Islets from WSD/CTR offspring secreted a greater amount of insulin in response to glucose ex vivo. We also found that maternal glucose tolerance and parity correlated with offspring glucose tolerance. Maternal WSD exposure results in persistently decreased α-cell mass in the three-year old offspring. WSD/CTR islets secreted greater amounts of insulin ex vivo, suggesting that these islets are primed to hyper-secrete insulin under certain metabolic stressors. Although WSD did not induce overt impaired glucose tolerance in dams or offspring, offspring born to mothers with higher glucose excursions during a glucose tolerance test were more likely to also show higher glucose excursions.


Parental rights and obligations of the unwed adolescent father.
Health care professionals dealing with teenage parents should be aware of the rights and responsibilities of teenage parents to their children. This article discusses the constitutional rights of unwed fathers, including adolescent fathers, the process of paternity determination including the right to counsel, the role of the guardian ad litem, the use of laboratory testing to establish paternity, and the statute of limitations for paternity actions. The federal program for child support enforcement and the financial obligations of the adolescent father are described. The legal rights of the father in custody disputes are outlined. The importance of health professionals being involved with the paternity adjudication process and being well informed of the legal rights and responsibilities of teenage parents have not received sufficient emphasis in the past.


Mast cell-mediated toxicity to schistosomula of Schistosoma mansoni: potentiation by exogenous peroxidase.
Mast cells, when incubated in vitro with hydrogen peroxide (H2O2) and iodide, are cytotoxic to schistosomula of Schistosoma mansoni, as determined morphologically by dye exclusion, motility, and refractility and by transmission and scanning electron microscopy. When intact mast cells were incubated with schistosomula, mast cell degranulation with extracellular release of mast cell granules (MCG) was only observed in the presence of added H2O2 (10(-4) M). The secreted MCG, which contain small amounts of endogenous peroxidase activity, adhered to the surface of schistosomula. By 15 to 30 min, the mast cell-H2O2 system in the presence of iodide (10(-4) M) produced marked disruption of the tegumental and internal structures of the schistosomula. No helminthic damage was noted if any component of the incubation mixture (mast cells, H2O2 or iodide) was omitted. MCG could substitute for intact mast cells in the H2O2 and iodide-dependent cytotoxic system; MCG-mediated killing of schistosomula was inhibited by the hemeprotein inhibitor azide, suggesting that the cytotoxic reaction required endogenous peroxidase. The cytotoxicity was increased by eosinophil peroxidase bound to the MCG surface. These findings suggest a mechanism by which mast cells may contribute to the host cytotoxic response to helminths. H2O2 formed by nearby inflammatory cells may induce mast cell secretion, and the released MCG, through their endogenous peroxidase content (or bound eosinophil or neutrophil peroxidase), may react with H2O2 and a halide to form a system toxic to the adjacent helminth.


Objective response to chemotherapy as a potential surrogate end point of survival in metastatic breast cancer patients.
To assess the validity of objective response to chemotherapy as a surrogate end point for survival in metastatic breast cancer. We carried out a meta-analysis on individual data from 2,126 metastatic breast cancer patients who were enrolled onto 10 randomized trials comparing standard versus intensified epirubicin-containing chemotherapy. The intensified chemotherapy was associated with a significantly higher tumor response rate compared with standard chemotherapy (pooled odds ratio for nonresponse, 0.60; 95% CI, 0.51 to 0.72). The intensified regimens also led to better (although not significant) survival (pooled odds ratio, 0.94; 95% CI, 0.86 to 1.04; P = .22). Tumor response was a highly significant predictor of survival (P < .0001). When tumor response was introduced in the Cox model, the hazard ratio in favor of experimental treatment changed from 0.94 to 1.005 (95% CI, 0.91 to 1.11; P = .92), indicating that no residual effect of the experimental treatment on survival was present once tumor response was adjusted for. This suggests that the overall survival benefit of intensified epirubicin was a result of the increase in response rate. The median survival time of patients with complete response and partial response was 28.8 months (95% CI, 25.4 to 45.3 months) and 21.3 months (95% CI, 19.2 to 22.4 months), respectively; whereas, the median survival time of patients with no response was 14.6 months (95% CI, 13.9 to 15.4 months). These results support the hypothesis that the achievement of an objective response to chemotherapy in metastatic breast cancer is associated with a true survival benefit. The potential role of objective response as a surrogate end point for survival in chemotherapy trials of metastatic breast cancer warrants further investigation.


SERPINB3 expression on B-cell surface in autoimmune diseases and hepatitis C virus-related chronic liver infection.
SERPINB3 is a serine protease inhibitor with pleiotropic functions. It is involved in several physiological and pathological processes, where it appears to exert antiapoptotic effects. Little is known about its expression on immune system cells, the major players in mechanisms of viral defense and autoimmune disorders. The aim of this study was to characterize the expression of SERPINB3 on the surface of peripheral blood mononuclear cell subsets in both normal subjects and in patients with chronic viral infections and autoimmune diseases. Sixty-two patients were analyzed by flow cytometric analysis, including 45 with hepatitis C virus (HCV)-related chronic liver disease and 17 with systemic lupus erythematosus (SLE). SERPINB3 was expressed on B lymphocytes in 79% of the controls, in 32% of the HCV-infected patients and in none of the SLE patients. Surface localization of SERPINB3 was confirmed by confocal microscopy. SERPINB3 positivity was associated with CD27 reactivity (r = 0.98), but not to other activation molecules (CD69, CD71, CD86 and CXCR3). SERPINB3 is physiologically expressed on the surface of CD27(+) B lymphocytes, but its expression is reduced in HCV viral infection and not detectable in SLE patients. These results may suggest a role for SERPINB3 in B-cell defects typically found in viral infections and autoimmune disorders.


Metapragmatic explicitation ability in children with typical language development: development and validation of a novel clinical assessment.
Speech-language practitioners recognise the importance of metapragmatic (MP) ability (the ability to explicitly reflect on pragmatic rules) in therapy for children with pragmatic and social communication difficulties. There is inconclusive evidence in the literature regarding both the development of metapragmatic ability in children with typical language and the expected levels of explicitation (reflection on pragmatic behaviours) in children's metapragmatic descriptions. The main purposes of this study were to investigate the reliability of a novel task of metapragmatic awareness (the Assessment of Metapragmatics or AMP) and to investigate typical developmental trends of metapragmatic ability and metapragmatic explicitation using the AMP task. Analysis of pooled data from 40 children with typical language development aged between six and eleven years and 48 children with communication impairments indicated that the AMP task had satisfactory internal consistency and inter-rater reliability. For children with typical language development, there was no relationship between gender and metapragmatic ability as measured by AMP. There was a linear relationship between age and AMP task scores and between age and explicitation. The scoring system used in the AMP task was sensitive to age-related changes in metapragmatic ability in a normative sample. The sophistication of metapragmatic awareness (explicitation) also increased with age. At age six years, children demonstrated metapragmatic awareness in their responses to 74% of AMP stimuli items; this increased to 95% of AMP items at ages 10-11 years. The AMP is a reliable measure of development in MP explicitation for children with satisfactory face validity in terms of acceptability to communication professionals and to child participants. From age six, children have some awareness of pragmatic acts and can identify and relate linguistic cues or pragmatic rules in atypical interactions of the type depicted in the AMP. The AMP task solicited significantly increased frequency of use of higher levels of MP explication beyond seven years of age in children with typical language development. Readers will explain the development, reliability and structure of a novel task that measures the ability of a child to understand and explain pragmatic rules. Readers will also identify age related changes in this ability in a sample of typically developing child participants.


Inactivation kinetics of mushroom tyrosinase in the dimethyl sulfoxide solution.
Mushroom tyrosinase (EC 126.96.36.199) is a kind of copper-containing oxidase that catalyzes both the hydroxylation of tyrosine into o-diphenols and the oxidation of o-diphenols into o-quinones and then forms brown or black pigments. In the present paper, the effects of dimethyl sulfoxide on the enzyme activity for the oxidation of L-3,4-dihydroxyphenylalanine (L-DOPA) have been studied. The results show that low concentrations of dimethyl sulfoxide (DMSO) can lead to reversible inactivation of the enzyme, and the IC(50) is estimated to be 2.45 M. Inactivation of the enzyme by DMSO is classified as mixed type. The kinetics of inactivation of mushroom tyrosinase at low concentrations of DMSO solution has been studied using the kinetic method of the substrate reaction. The rate constants of inactivation have been determined. The results show the free enzyme molecule is more fragile than the enzyme-substrate complex in the DMSO solution. It is suggested that the presence of the substrate offers marked protection of this enzyme against inactivation by DMSO.


An electrochemical immunosensor based on chemical assembly of vertically aligned carbon nanotubes on carbon substrates for direct detection of the pesticide endosulfan in environmental water.
A glassy carbon substrate was covalently modified with a mixed layer of 4-aminophenyl and phenyl via in situ electrografting of their aryldiazonium salts in acidic solutions. Single-walled carbon nanotubes (SWNTs) were covalently and vertically anchored on the electrode surface via the formation of amide bonds from the reaction between the amines located on the modified substrate and the carboxylic groups at the ends of the nanotubes. Ferrocenedimethylamine (FDMA) was subsequently attached to the ends of SWNTs through amide bonding followed by the attachment of an epitope, i.e., endosulfan hapten to which an antibody would bind. Association or dissociation of the antibody with the sensing interface causes a modulation of the ferrocene electrochemistry. Antibody-complexed electrodes were exposed to samples containing spiked endosulfan (unbound target analyte) in environment water and interrogated using the square wave voltammetry (SWV) technique. The modified sensing surfaces were characterized by atomic force microscopy, XPS, and electrochemistry. The fabricated electrochemical immunosensor can be successfully used for the detection of endosulfan over the range of 0.01-20 ppb by a displacement assay. The lowest detection limit of this immunosensor is 0.01 ppb endosulfan in 50 mM phosphate buffer at pH 7.0.


[Cystadenomas of the pancreas].
A case of pancreatic mucinous cystadenoma with borderline malignancy in a 70 year-old woman is presented. Cystadenomas are rare neoplasms, but should be suspected in patients with cystic lesions of the pancreas and no previous history of pancreatitis or abuse of alcohol.


Reasons for low adherence to diet-diaries issued to pediatric dental patients: a collective case study.
Dietary habits are an important etiological factor in the development of dental caries. Several tools, such as 24-h dietary recall (retrospective) and diet-diaries (prospective), have been recommended for dietary assessment in dental practice. Diet-diaries are commonly advocated as a tool for oral health education; however, low adherence is found to be a recognized downside of their use in dental settings, as well as nutritional research more widely. However, the reasons for poor adherence to diet-diaries remain unclear. This study aimed to explore the reasons for poor adherence to diet-diaries issued to children in a dental hospital setting. A qualitative collective case study design was employed to explore the use of diet-diaries as a health education tool. Twenty-eight data sources across 11 appointments included: observation of dentist-patient interactions, semi-structured interviews with child-parent dyads and dentists, in addition to documentary analysis of returned diet-diaries (this included 11 observations of dentist-patient interactions, 14 interviews with the child/parent dyads and dentists, and documentary analysis of three completed diet-diaries). Data from these multiple sources were integrated in a thematic analysis to identify themes and sub-themes. Two overarching themes were identified: 1) the diet-diary is perceived as a test which carries a potential for embarrassment and blame, which in turn generates defensive behavior from parents; and 2) parents' values, priorities, and circumstances affect the level of commitment to completing a diet-diary. Low adherence to diet-diary completion in clinical dentistry results from interacting factors related to the diet-diary itself, the patient, and the clinician. This study identifies a need for a more appropriate tool for dietary assessment that is patient-centered and compatible with modern lifestyles.


Processing of tumor antigen differentially impacts the development of helper and effector CD4+ T-cell responses.
CD4(+) T cells contribute to the antitumor T-cell response as both effectors that promote tumor rejection and helpers that facilitate the activation of other antitumor effector cells, such as CD8(+) T cells. Maximal engagement of both effector and helper CD4(+) T-cell responses is a desirable attribute of cancer vaccines. We have employed the B16F10 murine melanoma model and a series of recombinant adenovirus (Ad) vaccines expressing mutant forms of the tumor antigen, dopachrome tautomerase, to investigate the relationship between antigen processing and the antitumor CD4(+) T-cell response. Our results have revealed an unexpected dichotomy in the generation of helper and effector CD4(+) T-cell responses where CD4(+) T effector responses are dependent upon protein processing and trafficking, whereas CD4(+) T helper responses are not. The results have important implications for strategies aimed at augmenting antigen immunogenicity by altering intracellular processing and localization.


Medical and surgical management of idiopathic intracranial hypertension in pregnancy.
Idiopathic intracranial hypertension (IIH) is a syndrome of increased intracranial pressure without hydrocephalus or mass lesion with elevated cerebrospinal fluid (CSF) pressure but otherwise normal CSF composition. It has been found that pregnancy occurs in IIH patients at about the same rate as in the general population, that IIH can occur in any trimester of pregnancy, that patients have the same spontaneous abortion rate as the general population, and that the visual outcome is the same as for nonpregnant patients with IIH. Although it is also stated that pregnant patients with IIH should be managed and treated the same way as any other patient with IIH, the use of imaging and drug contraindications do make a difference between the two groups. The treatment has two major goals, which are to preserve vision and to improve symptoms. The medical therapy includes weight control, nonketotic diet, serial lumbar punctures, diuretics, steroids, and certain analgesics. When medical therapy fails, surgical procedures should be considered. The two main procedures are optic nerve sheath fenestration and lumboperitoneal shunt. Anesthetic considerations in the pregnant patient are an additional factor when surgeries are contemplated. It is also noted that therapeutic abortion to limit progression of disease is not indicated and that subsequent pregnancies do not increase the risk of recurrence.