Domestic violence is associated with environmental suppression of IQ in young children.
Research suggests that exposure to extreme stress in childhood, such as domestic violence, affects children's neurocognitive development, leading to lower intelligence. But studies have been unable to account for genetic influences that might confound the association between domestic violence and lower intelligence. This twin study tested whether domestic violence had environmentally mediated effects on young children's intelligence. Children's IQs were assessed for a population sample of 1116 monozygotic and dizygotic 5-year-old twin pairs in England. Mothers reported their experience of domestic violence in the previous 5 years. Ordinary least squares regression showed that domestic violence was uniquely associated with IQ suppression in a dose-response relationship. Children exposed to high levels of domestic violence had IQs that were, on average, 8 points lower than unexposed children. Structural equation models showed that adult domestic violence accounted for 4% of the variation, on average, in child IQ, independent of latent genetic influences. The findings are consistent with animal experiments and human correlational studies documenting the harmful effects of extreme stress on brain development Programs that successfully reduce domestic violence should also have beneficial effects on children's cognitive development.


Investigational growth factors utilized in animal models of spinal fusion: Systematic review.
Over 400000 Americans annually undergo spinal fusion surgeries, yet up to 40% of these procedures result in pseudoarthrosis even with iliac crest autograft, the current "gold standard" treatment. Tissue engineering has the potential to solve this problem via the creation of bone grafts involving bone-promoting growth factors (e.g., bone morphogenetic protein 2). A broad assessment of experimental growth factors is important to inform future work and clinical potential in this area. To date, however, no study has systematically reviewed the investigational growth factors utilized in preclinical animal models of spinal fusion. To review all published studies assessing investigational growth factors for spinal fusion in animal models and identify promising agents for translation. We conducted a systematic review of the literature using PubMed, Embase, Cochrane Library, and Web of Science databases with searches run on May 29th, 2018. The search query was designed to include all non-human, preclinical animal models of spinal fusion reported in the literature without a timespan limit. Extracted data for each model included surgical approach, level of fusion, animal species and breed, animal age and sex, and any other relevant characteristics. The dosages/sizes of all implant materials, spinal fusion rates, and follow-up time points were recorded. The data were analyzed and the results reported in tables and text. PRISMA guidelines were followed for this systematic review. Twenty-six articles were included in this study, comprising 14 experimental growth factors: AB204 (n = 1); angiopoietin 1 (n = 1); calcitonin (n = 3); erythropoietin (n = 1); basic fibroblast growth factor (n = 1); growth differentiation factor 5 (n = 4), combined insulin-like growth factor 1 + transforming growth factor beta (n = 4); insulin (n = 1); NELL-1 (n = 5); noggin (n = 1); P-15 (n = 1); peptide B2A (n = 2); and secreted phosphoprotein 24 (n = 1). The fusion rates of the current gold standard treatment (autologous iliac crest bone graft, ICBG) and the leading clinically used growth factor (BMP-2) ranged widely in the included studies, from 0-100% for ICBG and from 13%-100% for BMP-2. Among the identified growth factors, calcitonin, GDF-5, NELL-1, and P-15 resulted in fusion rates of 100% in some cases. In addition, six growth factors - AB204, angiopoietin 1, GDF-5, insulin, NELL-1, and peptide B2A - resulted in significantly enhanced fusion rates compared to ICBG, BMP-2, or other internal control in some studies. Large heterogeneity in animal species, fusion method, and experimental groups and time points was observed across the included studies, limiting the direct comparison of the growth factors identified herein. Several promising investigational growth factors for spinal fusion have been identified herein; directly comparing the fusion efficacy and safety of these agents may inform clinical translation.


An AI-Enabled Dynamic Risk Stratification for Emergency Department Patients with ECG and CXR Integration.
Emergency department (ED) triage scale determines the priority of patient care and foretells the prognosis. However, the information retrieved from the initial assessment is limited, hindering the risk identification accuracy of triage. Therefore, we sought to develop a 'dynamic' triage system as secondary screening, using artificial intelligence (AI) techniques to integrate information from initial assessment data and subsequent examinations. This retrospective cohort study included 134,112 ED visits with at least one electrocardiography (ECG) and chest X-ray (CXR) in a medical center from 2012 to 2022. Additionally, an independent community hospital provided 45,614 ED visits as an external validation set. We trained an eXtreme gradient boosting (XGB) model using initial assessment data to predict all-cause mortality in 7 days. Two deep learning models (DLMs) using ECG and CXR were trained to stratify mortality risks. The dynamic triage levels were based on output from the XGB-triage and DLMs from ECG and CXR. During the internal and external validation, the area under the receiver operating characteristic curve (AUC) of the XGB-triage model was >0.866; furthermore, the AUCs of DLMs using ECG and CXR were >0.862 and >0.886, respectively. The dynamic triage scale provided a higher C-index (0.914-0.920 vs. 0.827-0.843) than the original one and demonstrated better predictive ability for 5-year mortality, 30-day ED revisit, and 30-day discharge. The AI-based risk scale provides a more accurate and dynamic stratification of mortality risk in ED patients, particularly in identifying patients who tend to be overlooked due to atypical symptoms.


Infections in "noninfectious" lung diseases.
Many chronic pulmonary diseases, including those that are not primarily infectious in etiology, have some aspects of their pathogenesis that are influenced by infectious organisms. Microorganisms may contribute to chronic lung diseases, either directly (i.e., overt infection) or indirectly, via the amplification of inflammatory pathways that are critical to host defense. As techniques for detecting and characterizing microorganisms have advanced, investigations of both infecting and colonizing organisms have yielded new insights into mechanisms of pulmonary disease. In addition, changes in patterns of infection and microbial resistance have important implications for treatment. Examples of these infectious-pulmonary associations, including Haemophilus influenzae infection and chronic obstructive pulmonary disease, nontuberculous mycobacteria and bronchiectasis, and human immunodeficiency virus and obstructive lung disease, are reviewed.


Gain-of-function mutations identify amino acids within transmembrane domains of the yeast vacuolar transporter Zrc1 that determine metal specificity.
Cation diffusion facilitator transporters are found in all three Kingdoms of life and are involved in transporting transition metals out of the cytosol. The metals they transport include Zn2+, Co2+, Fe2+, Cd2+, Ni2+ and Mn2+; however, no single transporter transports all metals. Previously we showed that a single amino acid mutation in the yeast vacuolar zinc transporter Zrc1 changed its substrate specificity from Zn2+ to Fe2+ and Mn2+ [Lin, Kumanovics, Nelson, Warner, Ward and Kaplan (2008) J. Biol. Chem. 283, 33865-33873]. Mutant Zrc1 that gained iron transport activity could protect cells with a deletion in the vacuolar iron transporter (CCC1) from high iron toxicity. Utilizing suppression of high iron toxicity and PCR mutagenesis of ZRC1, we identified other amino acid substitutions within ZRC1 that changed its metal specificity. All Zrc1 mutants that transported Fe2+ could also transport Mn2+. Some Zrc1 mutants lost the ability to transport Zn2+, but others retained the ability to transport Zn2+. All of the amino acid substitutions that resulted in a gain in Fe2+ transport activity were found in transmembrane domains. In addition to alteration of residues adjacent to the putative metal- binding site in two transmembrane domains, alteration of residues distant from the binding site affected substrate specificity. These results suggest that substrate selection involves co-operativity between transmembrane domains.


Evaluation of several respirometry-based activated sludge toxicity control strategies.
Four different strategies including influent storage and reintroduction, step-feeding, rapid sludge recycle and waste sludge storage were evaluated using the denitrification layout of the IWA simulation benchmark. The control objective was to minimise deterioration in effluent quality caused by a certain toxic input event. In these strategies the maximum specific respiration rate (Rmax) was selected as a measured and controlled variable. To simplify the analysis, the toxicant was assumed to be a soluble and nonbiodegradable substance. Two toxic influent files were developed with square-wave input lasting 3 hours. To detect the influent toxicity, a pseudo-online flow-through respirometer was applied. A number of simulations were performed and the results suggested that the influent storage and reintroduction strategy provided the most optimistic results and other strategies could not mitigate the toxic effect. The influent storage and reintroduction strategy strongly depended on reintroduction flow rate from the storage tank. The simulation according to reintroduction flow could estimate the time required for completely treating toxic wastewater stored in the storage tank. Also the IWA simulation benchmark was enhanced to evaluate toxicity effect on the activated sludge process.


Effects of dietary fermentable carbohydrates on energy metabolism in group-housed sows.
The effect of dietary nonstarch polysaccharide (NSP) content on the metabolic rate in group-housed sows was studied. Twelve groups of six nonpregnant sows were each fed one of four experimental diets similar in composition except for the starch and NSP content. Exchanging sugar beet pulp silage (SBPS) for tapioca created the difference in starch and NSP ratio in the diet. On a DM basis, diets contained 0, 10, 20, or 30% SBPS. Sows were group-housed and fed at 1.30 times the assumed maintenance energy requirements. Nitrogen and energy balances were measured per group during a 7-d experimental period, which was preceded by a 33-d adaptation period. Both digestibility and metabolizability of energy decreased with increasing dietary SBPS content (P < 0.05). Heat production and energy retention were unaffected by the exchange of starch for NSP (P > 0.1). Based on energy retention data and apparent fecal digestibilities of crude protein, crude fat, starch, and NSP, the estimated net energy value of fermented NSP was 13.4 kJ/g. The present study shows that group-housed sows are capable of using energy from fermented NSP (i.e., NSP from SBPS) as efficiently as energy from digested starch (i.e., starch from tapioca).


Within-family processes: Interparental and coparenting conflict and child adjustment.
Previous studies have found evidence that interparental conflict, parents' coparenting behavior, and children's adjustment are reciprocally related. Most prior research, however, has failed to empirically distinguish between-family differences from within-family changes, limiting our understanding of how within-family fluctuations in each construct may be interrelated over time. In the present study, we focused on within-family associations among interparental conflict factors (i.e., verbal aggression and withdrawing), coparenting conflict, and children's internalizing and externalizing problems. Longitudinal data were drawn from 5 annual waves of survey data from 537 German families (i.e., mothers, fathers, and a focal child) in the German Family Panel (pairfam) study (Brüderl et al., 2015; Huinink et al., 2011). Data were analyzed with random intercept cross-lagged panel models, which partition variance into between- and within-person (or family) components in longitudinal data. Cross-lagged analyses of within-family variance revealed that fluctuations in interparental conflict did not predict child problems, but higher than typical child externalizing problems increased fathers' withdrawal and coparenting conflict in the future. Higher than average coparenting conflict within a given family predicted reductions in interparental verbal aggression, less maternal withdrawal, and fewer child externalizing problems. The findings demonstrate that analyses of within-family associations may provide new insights on mutual influences that unfold across time within families and are of particular importance for informing practice. (PsycINFO Database Record


Sodium saccharin inhibits adenylyl cyclase activity in non-taste cells.
We have studied the in vitro effect of sodium saccharin (NaSacch) on the rat adipocyte adenylyl cyclase complex. NaSacch (2.5-50 mM) inhibited significantly in a dose-dependent manner basal and isoproterenol-stimulated cAMP accumulation on isolated rat adipocytes. Similarly, NaSacch (2.5-50 mM) inhibited forskolin-stimulated adenylyl cyclase activity measured in the presence of Mg(2+)-ATP on adipocyte, astrocyte and thyrocyte membrane fractions. In contrast, NaSacch did not inhibit but slightly increased the forskolin-stimulated adenylyl cyclase activity measured in the presence of Mn(2+)-ATP and GDP beta S, a stable GDP analogue. The effect of NaSacch was not mediated through either the A1-adenosine receptor (A1R) or the alpha 2-adrenergic receptor (alpha 2AR). The inhibitory effect of NaSacch was additive to that of A1R agonist and was not blocked by the addition of the alpha 2AR antagonist RX 821002. Pretreatment of adipocytes with pertussis toxin slightly attenuated but did not abolish the inhibitory effect of NaSacch on forskolin-stimulated adenylyl cyclase activity on membrane fractions. These data suggest that the inhibitory effect of NaSacch on forskolin stimulated-adenylyl cyclase in adipocytes does not imply only Gi protein but also other direct or indirect inhibitory pathway(s) which remain to be determined.


Neurocognitive status and return to work after moderate to severe traumatic brain injury.
To examine the relationship of cognitive status to employment outcomes at 1-year post moderate-severe traumatic brain injury (TBI), using a brief telephone-administered instrument. Research Method/Design: Prospective longitudinal study in which 320 people with moderate-severe TBI, all employed at injury, were enrolled during inpatient rehabilitation and evaluated at 1-year postinjury. Follow-up measures included whether and when participants had returned to work (RTW), and cognitive status assessed with the Brief Test of Adult Cognition by Telephone (BTACT). Multivariable logistic regression and survival analyses were used to assess the contribution of BTACT (overall and subscale scores) to employment outcomes, controlling for covariates with known associations to those outcomes, including demographic variables, injury severity, and driving status. Fewer than 40% of participants (n = 124) were employed at 1-year follow-up. BTACT scores were strongly associated with RTW even after controlling for known covariates. Females had faster and higher rates of RTW compared to males. Resumption of driving and injury severity were also related to RTW. Neurocognitive status is a potentially modifiable factor with an important relationship to RTW following TBI. Vocational rehabilitation efforts should provide cognitive remediation or compensation as well as addressing transportation barriers. As a brief telephone-based assessment, the BTACT offers a new and efficient tool for evaluation of episodic memory and executive function. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


[The experiment of participatory mapping in order to construct a cartographical alternative to the FHS].
Maps and mapping procedures are useful tools for systematic interpretation and evaluation and for reporting of results to management. Applied to the Family Health Strategy (FHS), these maps permit the demarcation of the territory and the establishment of links between the territory, its population and health services. In this paper the use of maps by the FHS in 17 municipalities in northern and northeastern Brazil is studied and the process of demarcation and digitization of areas with the participation of teams is described. The survey conducted using questionnaires and discussion workshops showed that difficulties still prevail in reconciling the map (drawing) produced at the local level with maps produced by other government sectors. In general, the maps used at local level employ their own references, which prevent the interplay of information with other cartographic documents and their full use as a tool for evaluation and management. The combination of participatory mapping tools, associated with Geographic Information Systems (GIS) applications proposed in this paper, represents an alternative to mapping the territory of operations of FHS teams, as well as a reflection on the concept of territory and operation by the FHS.


The general anaesthetic etomidate inhibits the excitability of mouse thalamocortical relay neurons by modulating multiple modes of GABAA receptor-mediated inhibition.
Modulation of thalamocortical (TC) relay neuron function has been implicated in the sedative and hypnotic effects of general anaesthetics. Inhibition of TC neurons is mediated predominantly by a combination of phasic and tonic inhibition, together with a recently described 'spillover' mode of inhibition, generated by the dynamic recruitment of extrasynaptic γ-aminobutyric acid (GABA)A receptors (GABAA Rs). Previous studies demonstrated that the intravenous anaesthetic etomidate enhances tonic and phasic inhibition in TC relay neurons, but it is not known how etomidate may influence spillover inhibition. Moreover, it is unclear how etomidate influences the excitability of TC neurons. Thus, to investigate the relative contribution of synaptic (α1β2γ2) and extrasynaptic (α4β2δ) GABAA Rs to the thalamic effects of etomidate, we performed whole-cell recordings from mouse TC neurons lacking synaptic (α1(0/0) ) or extrasynaptic (δ(0/0) ) GABAA Rs. Etomidate (3 μm) significantly inhibited action-potential discharge in a manner that was dependent on facilitation of both synaptic and extrasynaptic GABAA Rs, although enhanced tonic inhibition was dominant in this respect. Additionally, phasic inhibition evoked by stimulation of the nucleus reticularis exhibited a spillover component mediated by δ-GABAA Rs, which was significantly prolonged in the presence of etomidate. Thus, etomidate greatly enhanced the transient suppression of TC spike trains by evoked inhibitory postsynaptic potentials. Collectively, these results suggest that the deactivation of thalamus observed during etomidate-induced anaesthesia involves potentiation of tonic and phasic inhibition, and implicate amplification of spillover inhibition as a novel mechanism to regulate the gating of sensory information through the thalamus during anaesthetic states.


Effective breast cancer detection with film-screen mammography.
Non-visualization of the retromammary space and ribs has been a source of concern to mammographers. In six years, 186 cancers were detected in our experience of 10 034 self-referred asymptomatic women at the University of Michigan Breast Cancer Detection Demonstration Project. These cancers were used to analyze the need to visualize the retromammary space and ribs, or both sites, if adequate technical factors were used. All the cancers were analyzed for position on the film, number of films required for visualization, relationship of the tumor to the posterior edge of the film, number of occult tumors, tumor size, histologic type, sensitivity of detection method and the number of interval cancers. Of the 186 cancers, 168 (90%) were detected on mammograms. All of the cancers were visualized on the mediolateral view; three were not visualized on the craniocaudal view. Six per cent of the cancers were within 1 cm of the posterior edge of the film; the remaining 94% were located more anteriorly in the breast. The imaged tumors were smaller and had a significantly higher percentage of non-invasive cancers than found in a symptomatic clinical population. Therefore, mammography, using proper technique, will consistently permit visualization of cancer in the breast, regardless of tumor size, histologic type, or location in the breast.


Multicomponent shell traits are consistent with an individual recognition function of the appearance of common murre (Uria aalge) eggs: A biological replication study.
In dense breeding colonies, and despite having no nest structure, common murres (or guillemots: Uria aalge) are still able to identify their own eggs. Each female murre's egg is thought to be recognized individually by the shell's avian-perceivable traits. This is because the eggshells' visible traits conform to expectations of the identity-signaling hypothesis in that they show both high intraindividual repeatability and high interindividual variability. Identity signaling also predicts a lack of correlation between each of the putative multicomponent recognition traits, yielding no significant relationships between those eggshell traits that are generated by mutually exclusive physiological factors. Using a multivariate analysis across eggshell size and shape, avian-perceivable background coloration, spot (maculation) shape, and spot density, we detected no unexpected statistical correlations between Icelandic common murre egg traits lacking known physiological or mathematical relationships with one another. These results biologically replicate the conclusions of a recent eggshell trait study of Canadian common murres using similar methodology. We also demonstrate the use of static correlations to infer identity signaling function without direct behavioral observations, which in turn may also be applied to rare or extinct species and provide valuable insight into otherwise unknown communicative and behavioral functions.


A population study of the jugular foramen bridging of the human cranium.
The author previously proposed a simple standard for diagnosing the jugular foramen bridging in man. The incidence of this bridging trait was investigated according to that standard in nine cranial series of East Indians, Micronesians, Japanese, Ainu, Mongols, Aleuts, Alaskan Eskimos, Canadian Eskimos, and Ontario Iroquois. No sex difference in incidence of the trait was recognized. Side difference in trait incidence was also slight but was statistically significant in the combined series of all the population samples examined. The bridging trait occurred more frequently on the right side than on the left side. Occurrences of the bridging trait were definitely associated between sides. Incidence of the trait was less in East Indians, Ontario Iroquois, and Micronesians, but greater in Alaskan Eskimos and Canadian Eskimos, the incidences in Japanese, Ainu, Aleuts, and Mongols being intermediate. The differences in trait incidence among the nine population samples were considered to reflect the differences in genetic compositions of these specific populations.


[Experience with a protocol of systematic postfibrinolysis angioplasty in acute myocardial infarct].
Two hundred twenty one patients admitted for AMI in the CCU, and treated with systemic thrombolysis with streptokinase have been retrospectively analysed and divided in two groups: the first 98 patients (group A) were included in a research protocol: The following 123 patients (group B) represent the clinical application of thrombolytic therapy in our unit. In group A coronary arteriography in the first 48 hours (84 patients), and PTCA to the infarct related artery with significant stenosis (39 patients) were performed systematically. In group B, 54 patients had coronary arteriography PTCA was restricted to 12 patients with symptomatic ischemia. No significant differences in base line clinical parameters were detected between groups A and B. Total hospital mortality was 5% and similar in both groups. Reinfarction rate was greater in group A, 13% than in group B, 5%, but not significantly different. Reinfarction was related to PTCA (chi 2 test p less than 0.05). The incidence of post infarction angina was related to the existence of more than one diseased vessel. These data suggest that protocol PTCA post thrombolysis is not effective in reducing post infarction ischemia or mortality.


Interferometric microring-resonant 2 x 2 optical switches.
We present modeling and simulation results on a new family of waveguided interferometric 2 x 2 optical routing switches actuated by electro-optic or thermo-optic or all-optical control. Two pairs of coupled microring resonators provide two 3dB coupling regions within a compact Mach-Zehnder geometry. An index perturbation (delta)n of 2 x 10(-3) is sufficient to produce 100% 2 x 2 switching. This perturbation can be applied to one arm of the MZI or to the four rings in the device or to an additional ring that is coupled to one arm. We find that push-pull control is effective for switching: for example, when carriers are injected in one region and depleted in a corresponding second region. An optical transfer-matrix technique is employed to determine the electromagnetic response (the 1550-nm switching characteristics) of the three device-types. Microdisks can be employed instead of microrings, if desired.


Neurenteric cyst of the craniocervical junction in an infant.
A 1-year-old boy presented with an extremely rare neurenteric cyst of the craniocervical junction manifesting as weakness in all extremities, slowly progressing over 2 months with rapid deterioration during the last few days. Neurological examination on admission showed tetraparesis with hyper-reflexia in the extremities. Magnetic resonance imaging demonstrated an intradural extramedullary cystic lesion located ventrally to the cord, extending from the craniocervical junction to the C3 level. The cyst wall was not enhanced with contrast medium, and the cyst content was isointense to the cerebrospinal fluid. He underwent total removal of the cyst through a left suboccipital craniectomy with C1 hemilaminectomy. The lesion had not adhered to the surrounding structures except for attachment to the left C2 nerve root outlet. Histological examination of the surgical specimen revealed typical neurenteric cyst with single layer epithelium. His symptoms improved significantly after the surgery, and he suffered no recurrence during the 2-year follow-up period. Neurenteric cyst should be considered in the differential diagnosis of intradural extramedullary cystic lesion located ventrally to the cord at the craniocervical junction in infants. Early surgical removal is recommended.


Assessing Rural Sustainable Development potentialities using a Dominance-based Rough Set Approach.
Rural Development is a priority in Europe and it is supported by specific, financial programmes. At the same time, sustainability is the key word for the European Union to construct programmes and policies for all human activities. However, measuring sustainability of rural areas is not easy, due to their particular features. The improvement of knowledge on sustainability in rural areas is important to build long term policies and strategies for those territories. The objective of this study is the development of a decision support system based on the Dominance-based Rough Set Approach (DRSA), to assess the level of Rural Sustainable Development in specific areas. We used DRSA to analyze the level of sustainability of the 92 municipalities of the Region of Umbria, Italy. The results were synthesized in a final ranking, taking into account the equilibrium and the integration between development and sustainability of each municipality. DRSA showed a high potential in the context of management or planning, and for supporting Decision Makers. DRSA is able to give a ranking as well as an explanation of the main factors driving sustainable development in rural areas.


Predicting the bioconcentration of fragrance ingredients by rainbow trout using measured rates of in vitro intrinsic clearance.
Bioaccumulation in aquatic species is a critical end point in the regulatory assessment of chemicals. Few measured fish bioconcentration factors (BCFs) are available for fragrance ingredients. Thus, predictive models are often used to estimate their BCFs. Because biotransformation can reduce chemical accumulation in fish, models using QSAR-estimated biotransformation rates have been developed. Alternatively, biotransformation can be measured by in vitro methods. In this study, biotransformation rates for nine fragrance ingredients were measured using trout liver S9 fractions and used as inputs to a recently refined in vitro-in vivo extrapolation (IVIVE) model. BCFs predicted by the model were then compared to (i) in vivo BCFs, (ii) BCFs predicted using QSAR-derived biotransformation rates, (iii) BCFs predicted without biotransformation, and (iv) BCFs predicted by a well-known regression model. For fragrance ingredients with relatively low (<4.7) log K(OW) values, all models predicted BCFs below a bioaccumulation threshold of 1000. For chemicals with higher (4.7-5.8) log K(OW) values, the model incorporating measured in vitro biotransformation rates and assuming no correction for potential binding effects on hepatic clearance provided the most accurate predictions of measured BCFs. This study demonstrates the value of integrating measured biotransformation rates for prediction of chemical bioaccumulation in fish.


Expression of p55 (Tac) interleukin-2 receptor (IL-2R), but not p75 IL-2R, in cultured H-RS cells and H-RS cells in tissues.
The authors studied the secretion of interleukin-2 (IL-2), the expression of interleukin-2 receptors (IL-2R; p55/Tac and p75), and the response to exogenous IL-2 by cultured Hodgkin's Reed-Sternberg cells (cell lines HDLM-1, HDLM-1d, and KM-H2) and T cells (H9, HuT78, HuT102, MOLT-4, and MT-2). All of these cells did not produce IL-2 or produced it in undetectable amounts, and their growth was not affected by the addition of anti-IL-2 or anti-IL-2R antibodies. This indicates that H-RS cells in long-term culture, as well as T cells, can grow independently of IL-2. The three H-RS cell lines, as well as two of the T-cell lines (HuT102 and MT-2), expressed Tac, whereas the other three T-cell lines were Tac negative. Expression of p75 was noted in the two Tac-positive T-cell lines, but not in cultured H-RS cells. The expression of Tac and p75 in HuT102 and MT-2 cells correlated well with their capacity to proliferate on treatment with exogenous IL-2. On IL-2 treatment, nucleic-acid uptake in Tac/p75-positive T cells increased approximately four- to sixfold, whereas the Tac/p75-negative T cells did not show increased proliferation. Unlike the T cells, the Tac-positive H-RS cells did not respond to IL-2. The lack of a proliferative response to IL-2 appears to be related to the absence of p75 in H-RS cells. A similar pattern (Tac positivity and p75 negativity) was noted in H-RS cells in lymph nodes involved by Hodgkin's disease. Thus the exogenous IL-2 released by surrounding T lymphocytes may not cause the proliferative activity of H-RS cells because of the lack of high-affinity IL-2 receptors in the latter cells. In contrast to H-RS cells in culture, H-RS cells in tissues were stained by a specific anti-IL-2 monoclonal antibody. This indicates that the expression of IL-2 or an IL-2-like substance by H-RS cells in tissues may be responsible, in part, for the great increase in the number of reactive T lymphocytes in tissues involved by Hodgkin's disease.


Immortal time bias in drug safety cohort studies: spontaneous abortion following nonsteroidal antiinflammatory drug exposure.
Experimental research of drug safety in pregnancy is generally not feasible because of ethical issues. Therefore, most of the information about drug safety in general and teratogenicity in particular is obtained through observational studies, which require careful methodologic design to obtain unbiased results. Immortal time bias occurs when some cases do not "survive" sufficient time in the study, and as such, they have reduced chances of being defined as "exposed" simply because the durations of their follow-ups were shorter. For example, studies that examine the risk for spontaneous abortions in women exposed to a drug during pregnancy are susceptible to immortal time bias because the chance of drug exposure increases the longer a pregnancy lasts. Therefore, the drug tested may falsely be found protective against the outcome tested. The objective of the current study was to illustrate the extent of immortal time bias using a cohort study of pregnancies assessing the risk for spontaneous abortions following nonsteroidal antiinflammatory drug exposure. We assembled 3 databases containing data on spontaneous abortions, births and drug dispensions to create the present study's cohort. The risk for spontaneous abortion was assessed using 2 statistical analysis methods that were compared for 2 definitions of exposure (dichotomous, exposed vs unexposed, regular Cox regression vs Cox regression with time-varying exposure). Significant differences were found in the risk for spontaneous abortions between the 2 statistical methods, both for groups and for most specific nonsteroidal antiinflammatory drugs (nonselective Cox inhibitors - hazard ratio, 0.70; 95% confidence interval, 0.61-0.94 vs hazard ratio, 1.10; 95% confidence interval, 0.99-1.22 for dichotomous vs time-varying exposure analyses, respectively). Furthermore, a significant correlation was found between the median misclassified immortal time for each drug and the extent of the bias. Immortal time bias can easily occur in cohort studies assessing the risk for adverse pregnancy outcomes following exposure to drugs. One way to prevent such a bias is by defining exposure only from the time of exposure during follow-up onward using a time-varying exposure analysis.


[Evaluation of the analgesic effect of UP 341-01 in patients presenting with acute pain in ORL].
The authors report the results obtained with a new analgesic, UP 341.01, which is a bioprecursor of paracetamol. Two groups of patients with acute pain, due to suppurative acute otitis media before myringotomy, were given an intravenous injection of 1 or 2 g of UP 341.01 respectively. Changes in the severity of pain were assessed over five hours by means of a verbal five point scoring system. During this study, UP 341.01 proved efficient and well tolerated.


Uterine torsion and uterine tear in a mare.
A 15-year-old Standard-bred mare was examined because of signs of abdominal discomfort in late gestation. Palpation per rectum revealed tight broad ligaments above and below the uterus, with the right broad ligament running across the top of the uterine body down toward the left, ventral side of the abdomen. A diagnosis of counterclockwise uterine torsion was made and surgical correction was approached via a left, flank laparotomy with the horse standing. The uterus was repositioned and a uterine tear encompassing 180 degrees of the uterine surface was found in the lateral, uterine body just cranial to the cervix. A live colt was delivered vaginally after uterine repositioning and the laparotomy incision was closed. The uterine tear was then repaired via a blind, vaginal approach. The mare was discharged 10 days after surgery. Repair per vaginum of a uterine tear is presented as an alternative treatment in cases for which the tear is recent, abdominal contamination is minimal, and the tear is easily accessible from the vaginal approach.


Influence of stabilizing components on the integrity of antitumor liposomes loaded with lipophilic prodrug in the bilayer.
Previously, we proposed a liposomal formulation of melphalan (Mlph)-a chemotherapeutic alkylating agent-incorporated in a fluid lipid bilayer in the form of dioleoylglyceride ester. In this work, we compared the stabilizing effect of different amphiphiles included in the Mlph-liposomes, such as phosphatidylinositol (PI), ganglioside GM1, a conjugate of N-carboxymethyl-modified oligoglycine with dioleoylphosphatidylethanolamine (acidic lipopeptide), and polyethylene glycol (2000 Da) conjugated with dipalmitoylphosphatidylethanolamine (PEG-lipid), upon incubation in human serum. Mean hydrodynamic diameter values (86-90 nm) were similar among different liposome samples, while zeta potential values considerably varied. The formulations were incubated in human serum at 37 °C for different time intervals up to 24 h. Liposome integrity was evaluated by changes in fluorescence upon leakage of calcein or disruption of Förster resonance energy transfer between donor and acceptor fluorescent lipid probes in the bilayer. The best stabilization of liposomes was achieved upon the addition of ganglioside GM1 or the acidic lipopeptide. Inclusion of 10 mol% PI improved liposome stability only for the first 4 h of incubation. Pegylated liposomal formulations of melphalan lipophilic prodrug with fluid phase bilayer were the least stable, which is probably due to the propensity of the PEG-lipid to exit liposome membranes. Cholesterol-containing bilayers of liquid ordered phase, supplemented with sufficient amounts of the PEG-lipid, showed good stability in serum.


Development of a new fluorescent angiotensin II probe.
Angiotensin II (ANG II) was conjugated to polystyrene Latex fluorescent microspheres (0.5 or 0.05 micron diam) with carbodiimide. Biological activity of the ANG II-conjugated microspheres (ANG II microspheres) was assessed in dispersed hepatocytes. The 0.05 micron ANG II microspheres inhibited glucagon-stimulated adenosine 3',5'-cyclic monophosphate accumulation and stimulated phosphorylase activity in hepatocytes, whereas the 0.5 micron ANG II microspheres only stimulated phosphorylase activity. The biological activity of the ANG II microspheres was caused by the conjugated ANG II and not by "free" ANG II associated with the spheres or by trypsin-like activity of hepatocytes causing release of ANG II from the microspheres. Binding of 0.05 micron ANG II to hepatocytes was readily observed with fluorescence microscopy. Little, if any, binding was observed with microspheres without conjugated ANG II. This fluorescent preparation of ANG II may have great utility in the study of receptor behavior after binding in individual cells.


Pharmacokinetics and pharmacogenetics of Gemcitabine as a mainstay in adult and pediatric oncology: an EORTC-PAMM perspective.
Gemcitabine is an antimetabolite ranking among the most prescribed anticancer drugs worldwide. This nucleoside analog exerts its antiproliferative action after tumoral conversion into active triphosphorylated nucleotides interfering with DNA synthesis and targeting ribonucleotide reductase. Gemcitabine is a mainstay for treating pancreatic and lung cancers, alone or in combination with several cytotoxic drugs (nab-paclitaxel, cisplatin and oxaliplatin), and is an option in a variety of other solid or hematological cancers. Several determinants of response have been identified with gemcitabine, i.e., membrane transporters, activating and inactivating enzymes at the tumor level, or Hedgehog signaling pathway. More recent studies have investigated how germinal genetic polymorphisms affecting cytidine deaminase, the enzyme responsible for the liver disposition of gemcitabine, could act as well as a marker for clinical outcome (i.e., toxicity, efficacy) at the bedside. Besides, constant efforts have been made to develop alternative chemical derivatives or encapsulated forms of gemcitabine, as an attempt to improve its metabolism and pharmacokinetics profile. Overall, gemcitabine is a drug paradigmatic for constant searches of the scientific community to improve its administration through the development of personalized medicine in oncology.


Calcifying epithelial odontogenic tumor showing microscopic features of potential malignant behavior.
Calcifying epithelial odontogenic tumor (CEOT) is a rare benign, but locally aggressive, odontogenic tumor, and only 2 cases of malignant CEOT are reported in the literature. We describe a case of an atypical CEOT that penetrates the blood vessels, invades bone, and perforates the cortical plates of the mandible. On histologic examination, it shows marked pleomorphism and numerous mitotic figures, including a tripolar mitotic figure. Proliferating activity was found to be 5 times higher than typical CEOTs as demonstrated by the proliferating index, Ki-67, and analyzed by a computerized image analysis system. The Ki-67 labeling index of this case was also compared to various previously reported benign and malignant neoplasms. Although there is no clinical finding of metastasis, we believe this neoplasm has malignant potential on the basis of the histologic features of vascular invasion, significant mitotic activity, atypical mitotic figures, and an increased proliferating index.


Magnesium deficiency up-regulates Myod expression in rat skeletal muscle and C2C12 myogenic cells.
Magnesium (Mg) deficiency induces the production of free radicals, increases cytosolic ionized calcium concentration, and modulates the function of skeletal muscle in rats. The present study examined the effects of Mg deficiency on the gene expression of molecules related to myogenesis in the gastrocnemius muscle as well as in C2C12 myogenic cells. Ingestion of an Mg-deficient diet resulted in a lower weight of the gastrocnemius muscle and higher concentration of muscular TBARSs, an index of oxidative stress. Mg deficiency also enhanced the expression of Myod and myogenin. In vivo effects of Mg deficiency on myogenic gene expression were partially reproduced in in vitro C2C12 cells; expression of Myod was up-regulated by a mixed culture of myoblasts and myotubes with Mg-deficient medium, which related to the simultaneous up-regulation of Myhc IIb, a myotube-specific protein. The culture with Mg-deficient medium did not increase the gene transcript level of HO-1, another marker of oxidative stress, suggesting that Mg deficiency-induced Myod expression does not result from oxidative stress. Furthermore, oxidative stress induced by hydrogen peroxide did not increase Myod expression, whereas the expression of Myod, myogenin and Myhc IIb was decreased by oxidative stress from the initial phase of differentiation. The effects of Mg deficiency depended on the stages of myogenesis; myoblast culture in Mg-deficient differentiation medium did not affect the expression of Myod and Myhc IIb. The present study revealed stage-dependent effects of Mg deficiency on myogenesis.


How alcohol affects insulin-like growth factor-1's influences on the onset of puberty: A critical review.
Alcohol (ALC) is capable of delaying signs associated with pubertal development in laboratory animals, as well as in humans. The normal onset of puberty results from a timely increase in gonadotropin-releasing hormone (GnRH) secretion, which is associated with a gradual decline in prepubertal inhibitory influences, and the establishment of excitatory inputs that increase GnRH release, which together drive pubertal development. In recent years, insulin-like growth factor-1 (IGF-1) has emerged as a pivotal contributor to prepubertal GnRH secretion and pubertal development, whose critical actions are interfered with by ALC abuse. Here we review the neuroendocrine research demonstrating the important role that IGF-1 plays in pubertal development, and describe the detrimental effects and mechanisms of action of ALC on the onset and progression of pubertal maturation.


Lumped-parameters equivalent circuit for condenser microphones modeling.
This work presents a lumped parameters equivalent model of condenser microphone based on analogies between acoustic, mechanical, fluidic, and electrical domains. Parameters of the model were determined mainly through analytical relations and/or finite element method (FEM) simulations. Special attention was paid to the air gap modeling and to the use of proper boundary condition. Corresponding lumped-parameters were obtained as results of FEM simulations. Because of its simplicity, the model allows a fast simulation and is readily usable for microphone design. This work shows the validation of the equivalent circuit on three real cases of capacitive microphones, including both traditional and Micro-Electro-Mechanical Systems structures. In all cases, it has been demonstrated that the sensitivity and other related data obtained from the equivalent circuit are in very good agreement with available measurement data.


Antiapicoplast and gametocytocidal screening to identify the mechanisms of action of compounds within the malaria box.
Malaria remains a significant infectious disease that causes millions of clinical cases and >800,000 deaths per year. The Malaria Box is a collection of 400 commercially available chemical entities that have antimalarial activity. The collection contains 200 drug-like compounds, based on their oral absorption and the presence of known toxicophores, and 200 probe-like compounds, which are intended to represent a broad structural diversity. These compounds have confirmed activities against the asexual intraerythrocytic stages of Plasmodium falciparum and low cytotoxicities, but their mechanisms of action and their activities in other stages of the parasite's life cycle remain to be determined. The apicoplast is considered to be a promising source of malaria-specific targets, and its main function during intraerythrocytic stages is to provide the isoprenoid precursor isopentenyl diphosphate, which can be used for phenotype-based screens to identify compounds targeting this organelle. We screened 400 compounds from the Malaria Box using apicoplast-targeting phenotypic assays to identify their potential mechanisms of action. We identified one compound that specifically targeted the apicoplast. Further analyses indicated that the molecular target of this compound may differ from those of the current antiapicoplast drugs, such as fosmidomycin. Moreover, in our efforts to elucidate the mechanisms of action of compounds from the Malaria Box, we evaluated their activities against other stages of the life cycle of the parasite. Gametocytes are the transmission stage of the malaria parasite and are recognized as a priority target in efforts to eradicate malaria. We identified 12 compounds that were active against gametocytes with 50% inhibitory concentration values of <1 μM.


It takes three: selection, influence, and de-selection processes of depression in adolescent friendship networks.
The authors of this study tested a selection-influence-de-selection model of depression. This model explains friendship influence processes (i.e., friends' depressive symptoms increase adolescents' depressive symptoms) while controlling for two processes: friendship selection (i.e., selection of friends with similar levels of depressive symptoms) and friendship de-selection (i.e., de-selection of friends with dissimilar levels of depressive symptoms). Further, this study is unique in that these processes were studied both inside and outside the school context. The authors used a social network approach to examine 5 annual measurements of data in a large (N =847) community-based network of adolescents and their friends (M = 14.3 years old at first measurement). Results supported the proposed model: adolescents tend to select friends with similar levels of depression, and friends may increase each other's depressive symptoms as relationships endure. These two processes were most salient outside the school context. At the same time, friendships seemed to be ended more frequently if adolescents' level of depressive symptoms was dissimilar to that of their friends.


Oral health beliefs, knowledge, and behaviors in Northern California American Indian and Alaska Native mothers regarding early childhood caries.
To assess the oral health beliefs, knowledge, and behaviors related to early childhood caries (ECC) risk in a convenience sample of American Indian and Alaska Native (AIAN) mothers residing in rural Northern California communities. Fifty-three mothers of young children were recruited from three tribal communities in Northern California with the assistance of the California Rural Indian Health Board, Inc. and its California Tribal Epidemiology Center and Dental Support Center. Trained study staff administered questionnaires to obtain basic socio-demographic information, to survey participants on their oral health beliefs, knowledge, and behaviors as related to ECC risk, and to identify possible barriers to their accessing professional oral health care. Analyses of covariance were used to explore associations between socio-demographic indicators and oral health behaviors, after controlling for knowledge, beliefs and barriers to care. Overall, 53 percent of participants reported their oral health as "fair" or "poor." Mothers' education (high) and being employed were positively associated with better oral health behavior scores. Additionally, 72 percent of mothers reported having one or more barriers to oral health care including access. There was a significant relation (P = 0.03) between high number of reported barriers to oral health care and low oral health behavior scores. Despite generally high-level oral health knowledge, perceptions of self and child oral health remains low in this sample of AIAN mothers. Factors identified as being associated with oral health behaviors in this sample were similar to those found in other health disparities populations.


Differential assessment of financial and relationship distress: implications for couples therapy.
This study examined the role of financial conflicts, problem-solving communication deficits, and global relationship distress among couples in marital therapy and couples seeking assistance at a nonprofit agency providing financial counseling services. Analyses comparing these two groups of couples with each other and with a third group of couples from the general community yielded a two-component model for differential assessment and intervention with couples experiencing financial concerns. Differences in findings for husbands and wives provided additional implications for effective interventions with these couples.


[An automated unit for manual photometry and morphometry].
An automated unit for manually controlled photometry and morphometry is described. It enables the operator to carry out photometrical measurements according to the plug-method and morphometrical measurements with the help of an object-micrometer or some kind of a grid. The data obtained are stored in the "Elektronika D3-28" microcomputer to be statistically evaluated after the end of sampling. New variables can be obtained defined by the user as a product of some source variables or their inverses. The data and control structures of the system are described in detail.


Fluorescence correlation spectroscopy in cells: confinement and excluded volume effects.
Fluorescence correlation spectroscopy (FCS) has become an important technique in biophysical research, which is also used for in vivo studies of molecular mobilities in cells. We theoretically study how confinement or exclusion of the diffusing fluorescent molecules by a spherical region influences the measured autocorrelation function in an FCS experiment. It is shown that close to the boundary of the spherical region the diffusion time can be significantly changed due to the geometric restriction of the detection volume. This is important when quantitatively evaluating and interpreting FCS measurements in cells.


Mucopolysaccharidosis type II detection by Naïve Bayes Classifier: An example of patient classification for a rare disease using electronic medical records from the Canadian Primary Care Sentinel Surveillance Network.
Identifying patients with rare diseases associated with common symptoms is challenging. Hunter syndrome, or Mucopolysaccharidosis type II is a progressive rare disease caused by a deficiency in the activity of the lysosomal enzyme, iduronate 2-sulphatase. It is inherited in an X-linked manner resulting in males being significantly affected. Expression in females varies with the majority being unaffected although symptoms may emerge over time. We developed a Naïve Bayes classification (NBC) algorithm utilizing the clinical diagnosis and symptoms of patients contained within their de-identified and unstructured electronic medical records (EMR) extracted by the Canadian Primary Care Sentinel Surveillance Network (CPCSSN). To do so, we created a training dataset using published results in the scientific literature and from all MPS II symptoms and applied the training dataset and its independent features to compute the conditional posterior probabilities of having MPS II disease as a categorical dependent variable for 506497 male patients. The classifier identified 125 patients with the highest likelihood for having the disease and 18 features were selected to be necessary for forecasting. Next, a Recursive Backward Feature Elimination algorithm was employed, for optimal input features of the NBC model, using a k-fold Cross-Validation with 3 replicates. The accuracy of the final model was estimated by the Validation Set Approach technique and the bootstrap resampling. We also investigated that whether the NBC is as accurate as three other Bayesian networks. The Naïve Bayes Classifier appears to be an efficient algorithm in assisting physicians with the diagnosis of Hunter syndrome allowing optimal patient management.


[ISO 9000: guidelines for a total quality system in health].
The Italian National Health System has recently been revised and reorganized. In the new scenario, the quality of the service being provided is considered extremely important. The international ISO 9000 standard has made it possible to implement a total-quality management system that can be documented and certified independently by a third party. Several hospitals in Italy and abroad have implemented a total-quality system according to ISO 9000 standards in order to provide a service that can satisfy the expectations of the patients in a controlled and efficient way. This article describes ISO 9000, proposes its application to ensure quality in the structures and organizations involved in the national health system and reports several examples of how the standard has been implemented in hospitals.


Volumetric quantitation by MRI in primary progressive multiple sclerosis: volumes of plaques and atrophy correlated with neurological disability.
In primary progressive multiple sclerosis (PPMS) abnormalities in brain magnetic resonance imaging (MRI) differ from abnormalities in other subtypes of multiple sclerosis (MS). It was investigated whether the extent of brain and spinal cord MRI abnormalities is reflected in the neurological disability in PPMS. Focal and diffuse changes and atrophy in central nervous system (CNS) in patients with PPMS (n = 28) and healthy controls (n = 20) were assessed by semi-automatic MRI segmentation and volumetric analysis. The measurements were related to neurological disability as expressed by the expanded disability status scale (EDSS), the regional functional scoring system (RFSS), the arm index and the ambulation index. Plaques in T1- and/or T2-weighted images were seen in all brains, while spinal plaques were detected in 23 of 28 patients (82%). The total volumes of brain and spinal cord were significantly smaller in patients than in controls (P = 0.001 and 0.000, respectively). The volumes of T1 or T2 lesions in the brain correlated to the ambulation index (r = 0.51, P = 0.005 and r = 0.53, P = 0.004, respectively). No correlations were detected between MRI measurements and total EDSS score, but relative brain atrophy correlated inversely with the total RFSS scores, poor arm index and higher cerebral disturbances (r = -0.53, P = 0.004; r = -0.53, P = 0.004; and r = -0.52, P = 0.005, respectively). Although the number of spinal T2 lesions correlated with sensory disturbances (r = 0.60, P = 0.001), no correlations were found between EDSS subscores and spinal cord atrophy. These findings show that marked atrophy of brain and spinal cord detected by volumetric quantitation correlates with neurological disability. This observation indicates the importance of neurodegenerative events in PPMS.


Development of Y chromosome intraspecific polymorphic markers in the Felidae.
Y chromosome haplotyping based on microsatellites and single nucleotide polymorphisms (SNPs) has proved to be a powerful tool for population genetic studies of humans. However, the promise of the approach is hampered in the majority of nonhuman mammals by the lack of Y-specific polymorphic markers. We were able to identify new male-specific polymorphisms in the domestic cat Felis catus and 6 additional Felidae species with a combination of molecular genetic and cytogenetic approaches including 1) identifying domestic cat male-specific microsatellites from markers generated from a male cat microsatellite-enriched genomic library, a flow-sorted Y cosmid library, or a Y-specific cat bacteria artificial chromosome (BAC) clone, (2) constructing microsatellite-enriched libraries from flow-sorted Y chromosomes isolated directly from focal wildcat species, and (3) screening Y chromosome conserved anchored tagged sequences primers in Felidae species. Forty-one male-specific microsatellites were identified, but only 6 were single-copy loci, consistent with the repetitive nature of the Y chromosome. Nucleotide diversity (pi) of Y-linked intron sequences (2.1 kbp) was in the range of 0 (tiger) to 9.95 x 10(-4) (marbled cat), and the number of SNPs ranged from none in the tiger to 7 in the Asian leopard cat. The Y haplotyping system described here, consisting of 4 introns (SMCY3, SMCY7, UTY11, and DBY7) and 1 polymorphic microsatellite (SMCY-STR), represents the first available markers for tracking intraspecific male lineage polymorphisms in Felidae species and promises to provide significant insights to evolutionary and population genetic studies of the species.


Integrated Analysis of Droxidopa for the Treatment of Neurogenic Orthostatic Hypotension in Patients with Parkinson Disease.
Neurogenic orthostatic hypotension (nOH) is associated with neurodegenerative conditions, may cause symptoms of end-organ hypoperfusion, increases fall risk, and can negatively impact quality of life. Droxidopa is approved for the treatment of symptomatic nOH in adults. As the largest subpopulation of patients with nOH has a diagnosis of Parkinson disease (PD), the efficacy and tolerability of droxidopa in patients with PD and nOH were examined using integrated clinical trial data. Post hoc analyses included data from the phase 3, randomized, placebo-controlled clinical trials of droxidopa (two short-term [1-2 weeks] trials and one medium-term [8-10 weeks] trial) in the subset of participants with PD and symptomatic nOH. Efficacy was assessed using standing blood pressure (BP) measurements and the Orthostatic Hypotension Questionnaire (OHQ), a patient-reported evaluation of nOH symptoms (Orthostatic Hypotension Symptom Assessment [OHSA]), and their impact (Orthostatic Hypotension Daily Activity Scale [OHDAS]). The analysis included 307 patients with PD (droxidopa, n = 150; placebo, n = 157). Compared with placebo, droxidopa significantly improved the OHQ composite score (P = 0.014), the OHSA composite score (P = 0.022), and the OHDAS composite score (P = 0.029) from baseline to end of study/week one. We found significant increases in standing mean systolic/diastolic BP for droxidopa versus placebo (P = 0.003/0.002). Adverse event (AE) rates were qualitatively similar between groups; the most frequently reported AEs in the droxidopa groups included headache, dizziness, nausea, and hypertension. These post hoc analyses suggest that droxidopa provides meaningful clinical benefits and is well tolerated in the treatment of symptomatic nOH in patients with PD.


Oil spill effects on macrofaunal communities and bioturbation of pristine marine sediments (Caleta Valdés, Patagonia, Argentina): experimental evidence of low resistance capacities of benthic systems without history of pollution.
The Patagonian coast is characterized by the existence of pristine ecosystems which may be particularly sensitive to oil contamination. In this study, a simulated oil spill at acute and chronic input levels was carried out to assess the effects of contamination on the macrobenthic community structure and the bioturbation activity of sediments sampled in Caleta Valdés creek. Superficial sediments were either noncontaminated or contaminated by Escalante crude oil and incubated in the laboratory for 30 days. Oil contamination induced adverse effects on macrobenthic community at both concentrations with, for the highest concentration, a marked decrease of approximately 40 and 55 % of density and specific richness, respectively. Besides the disappearance of sensitive species, some other species like Oligochaeta sp. 1, Paranebalia sp., and Ostracoda sp. 2 species have a higher resistance to oil contamination. Sediment reworking activity was also affected by oil addition. At the highest level of contamination, nearly no activity was observed due to the high mortality of macroorganisms. The results strongly suggest that an oil spill in this protected marine area with no previous history of contamination would have a deep impact on the non-adapted macrobenthic community.


Motivating parent support for physical activity: the role of framed persuasive messages.
Parent support for physical activity (PA) is a behavior unto itself that requires motivation. Persuasive messages may be one method for motivating parent support for their children's PA. Message framing is one strategy for optimizing the impact of messages. The current study examined the relative effectiveness of gain- versus loss-framed messages for encouraging parent support for children's PA. Regardless of message frame, parents had an increase in social cognitive antecedents (e.g. perceived behavioral control, intentions) and support for children's PA following message exposure.


Developmental determinants of cardiac sensitivity to hypoxia.
Cardiac sensitivity to oxygen deprivation changes significantly during ontogenetic development. However, the mechanisms for the higher tolerance of the immature heart, possibilities of protection, and the potential impact of perinatal hypoxia on cardiac tolerance to oxygen deprivation in adults have not yet been satisfactorily clarified. The hypoxic tolerance of an isolated rat heart showed a triphasic pattern: significant decrease from postnatal day 1 to 7, followed by increase to the weaning period, and final decline to adulthood. We have observed significant ontogenetic changes in mitochondrial oxidative phosphorylation and mitochondrial membrane potential, as well as in the role of the mitochondrial permeability transition pores in myocardial injury. These results support the hypothesis that cardiac mitochondria are deeply involved in the regulation of cardiac tolerance to oxygen deprivation during ontogenetic development. Ischemic preconditioning failed to increase tolerance to oxygen deprivation in the highly tolerant hearts of newborn rats. Chronic hypoxic exposure during early development may cause in-utero or neonatal programming of several genes that can change the susceptibility of the adult heart to ischemia-reperfusion injury; this effect is sex dependent. These results would have important clinical implications, since cardiac sensitivity in adult patients may be significantly affected by perinatal hypoxia in a sex-dependent manner.


Platelet surface glycoproteins. Studies on resting and activated platelets and platelet membrane microparticles in normal subjects, and observations in patients during adult respiratory distress syndrome and cardiac surgery.
The accurate definition of surface glycoprotein abnormalities in circulating platelets may provide better understanding of bleeding and thrombotic disorders. Platelet surface glycoproteins were measured on intact platelets in whole blood and platelet membrane microparticles were assayed in cell-free plasma using 125I-monoclonal antibodies. The glycoproteins (GP) studied were: GP Ib and GP IIb-IIIa, two of the major intrinsic plasma membrane glycoproteins; GMP-140, an alpha-granule membrane glycoprotein that becomes exposed on the platelet surface following secretion; and thrombospondin (TSP), an alpha-granule secreted glycoprotein that rebinds to the platelet surface. Thrombin-induced secretion in normal platelets caused the appearance of GMP-140 and TSP on the platelet surface, increased exposure of GP IIb-IIIa, and decreased antibody binding to GP Ib. Patients with adult respiratory distress syndrome had an increased concentration of GMP-140 and TSP on the surface of their platelets, demonstrating in vivo platelet secretion, but had no increase of platelet microparticles in their plasma. In contrast, patients after cardiac surgery with cardiopulmonary bypass demonstrated changes consistent with membrane fragmentation without secretion: a decreased platelet surface concentration of GP Ib and GP IIb with no increase of GMP-140 and TSP, and an increased plasma concentration of platelet membrane microparticles. These methods will help to define acquired abnormalities of platelet surface glycoproteins.


The Effect of the Coal Industry on Indoor Radon Concentrations in eMalahleni, Mpumalanga Province of South Africa.
South Africa has rich coal deposits concentrated in the northeast of the country, and as a result, most of the country's coal mining is located in this region. Two of the principal coalfields exploited are the Witbank and Highveld coalfields, located in the Mpumalanga province. Coal contains trace quantities of the naturally occurring radionuclides whose mass concentration can be enhanced by anthropogenic activity. The radioactive fallout from these activities could lead to elevated radon concentrations indoors. Two towns, Secunda and eMalahleni, were identified due to their proximity to coal-based industries. A previous study investigated whether these industries caused elevated radon levels in Secunda homes but found a lower-than-expected average concentration of 76.4 ± 7.6 Bq m-3. This was attributed to either the prevailing wind depositing the radioactive fallout to neighboring towns, such as eMalahleni, or the type of industrial activity. This paper builds on this study by investigating whether elevated radon levels are found in homes in eMalahleni. Measurements were performed in 22 homes during December 2019, and the average indoor radon concentration was calculated as 122.1 ± 8.5 Bq m-3. The cause of these elevated levels was then investigated, and it was found that even though the coal industry contributes to elevated radon levels, the town's underlying geology seems to be the primary contributor.


An inhibitory role for FAK in regulating proliferation: a link between limited adhesion and RhoA-ROCK signaling.
Focal adhesion kinase (FAK) transduces cell adhesion to the extracellular matrix into proliferative signals. We show that FAK overexpression induced proliferation in endothelial cells, which are normally growth arrested by limited adhesion. Interestingly, displacement of FAK from adhesions by using a FAK-/- cell line or by expressing the C-terminal fragment FRNK also caused an escape of adhesion-regulated growth arrest, suggesting dual positive and negative roles for FAK in growth regulation. Expressing kinase-dead FAK-Y397F in FAK-/- cells prevented uncontrolled growth, demonstrating the antiproliferative function of inactive FAK. Unlike FAK overexpression-induced growth, loss of growth control in FAK-/- or FRNK-expressing cells increased RhoA activity, cytoskeletal tension, and focal adhesion formation. ROCK inhibition rescued adhesion-dependent growth control in these cells, and expression of constitutively active RhoA or ROCK dysregulated growth. These findings demonstrate the ability of FAK to suppress and promote growth, and underscore the importance of multiple mechanisms, even from one molecule, to control cell proliferation.


How to Manage Self-Poisoning With Baclofen in Alcohol Use Disorder? Current Updates.
Specialists in addiction medicine continue to debate whether baclofen is still indicated to treat alcohol use disorders in view of conflicting results as to its efficacy. This review summarizes current knowledge on self-poisoning with baclofen focusing of alcohol-use disorder in order to provide an overview of the reliable scientific knowledge on management of such an intoxication. Moreover, as alcohol-dependent patients experience many psychiatric co-morbidities, the risk in suicide attempt using baclofen seems real. Numerous studies have suggested that patients given daily-doses of baclofen higher than 80 mg/day are more likely to attempt suicides than others. Following an ingestion of a large amount of baclofen, central nervous system depression is usually observed. Seizures require the patient to be admitted in intensive care unit and should be treated like other toxicological seizures. Cardiac complications include prolonged QTc interval, degree heart block, premature atrial contractions, and supraventricular tachycardia, hypotension and bradycardia. In cases of intoxication, the elimination half-life of baclofen may last between 12 and 36 h post-overdose and renal failure is known to delay its clearance. Rarely measured in clinical practice, the toxic level of baclofen blood level ranges from 1.1 to 3.5 mg/l, and coma or fatal intoxication are observed from 6 to 9.6 mg/l. Baclofen withdrawal has been observed but making the diagnosis of withdrawal in case of suspected self-poisoning is difficult as baclofen intoxication and baclofen withdrawal share many clinical signs. Admission to hospital to manage of suicide attempt with baclofen is mandatory and should not be limited to baclofen alone. It needs to include other aspects of the overall care of patients with alcohol disorders (psychological and psychosocial interventions, management of comorbid mental conditions and physical complications).


Circulating levels of soluble EMMPRIN (CD147) correlate with levels of soluble glycoprotein VI in human plasma.
Extracellular matrix metalloproteinase inducer (EMMPRIN; CD147), which binds to the platelet-specific collagen receptor glycoprotein (GP) VI, is expressed in a range of cell types including platelets and leukocytes, and has been implicated in neoplastic disease and atherosclerotic coronary disease. Both CD147 and GPVI can be shed from cell membranes and detected in plasma. However, while the relationship between soluble CD147 (sCD147), soluble GPVI (sGPVI) and standard markers of platelet activation has received little attention, such analysis may help reveal pathways mediating release of sCD147. We investigated the relationship between sCD147 and platelet markers including sGPVI, soluble and platelet-bound CD62P (P-selectin), active αIIbβ3 (assessed by PAC-1 binding) and platelet CD147 in 25 patients with stable angina pectoris (SAP), 13 patients with no coronary artery disease (CAD) and 10 healthy donors. Plasma levels of sCD147 significantly correlated with sGPVI (r = 0.46, p = .004), but did not correlate with any other platelet markers examined. Linear regression analysis identified that sCD147 levels could be predicted by sGPVI levels (β = .445, p = 0.003) and age (β = 0.304, p = 0.038), but were independent of potential clinical confounders such as CAD, diabetes and medication usage. As sCD147 strongly correlates with platelet-specific sGPVI, a common platelet source and/or mechanism of release may contribute to sCD147 levels in vivo.


Conditional biallelic Nf2 mutation in the mouse promotes manifestations of human neurofibromatosis type 2.
Hemizygosity for the NF2 gene in humans causes a syndromic susceptibility to schwannoma development. However, Nf2 hemizygous mice do not develop schwannomas but mainly osteosarcomas. In the tumors of both species, the second Nf2 allele is inactivated. We report that conditional homozygous Nf2 knockout mice with Cre-mediated excision of Nf2 exon 2 in Schwann cells showed characteristics of neurofibromatosis type 2. These included schwannomas, Schwann cell hyperplasia, cataract, and osseous metaplasia. Thus, the tumor suppressor function of Nf2, here revealed in murine Schwann cells, was concealed in hemizygous Nf2 mice because of insufficient rate of second allele inactivation in this cell compartment. The finding of this conserved function documents the relevance of the present approach to model the human disease.


Is IPT time-limited psychodynamic psychotherapy?
Interpersonal psychotherapy (IPT) has sometimes but not always been considered a psychodynamic psychotherapy. The authors discuss similarities and differences between IPT and short-term psychodynamic psychotherapy (STPP), comparing eight aspects: 1) time limit, 2) medical model, 3) dual goals of solving interpersonal problems and syndromal remission, 4) interpersonal focus on the patient solving current life problems, 5) specific techniques, 6) termination, 7) therapeutic stance, and 8) empirical support. The authors then apply both approaches to a case example of depression. They conclude that despite overlaps and similarities, IPT is distinct from STPP.


Stromal PTEN Regulates Extracellular Matrix Organization in the Mammary Gland.
The organization of the extracellular matrix has a profound impact on cancer development and progression. The matrix becomes aligned throughout tumor progression, providing "highways" for tumor cell invasion. Aligned matrix is associated with breast density and is a negative prognostic factor in several cancers; however, the underlying mechanisms regulating this reorganization remain poorly understood. Deletion of the tumor suppressor Pten in the stroma was previously shown to promote extracellular matrix expansion and tumor progression. However, it was unknown if PTEN also regulated matrix organization. To address this question, a murine model with fibroblast-specific Pten deletion was used to examine how PTEN regulates matrix remodeling. Using second harmonic generation microscopy, Pten deletion was found to promote collagen alignment parallel to the mammary duct in the normal gland and further remodeling perpendicular to the tumor edge in tumor-bearing mice. Increased alignment was observed with Pten deletion in vitro using fibroblast-derived matrices. PTEN loss was associated with fibroblast activation and increased cellular contractility, as determined by traction force microscopy. Inhibition of contractility abrogated the increased matrix alignment observed with PTEN loss. Murine mammary adenocarcinoma cells cultured on aligned matrices derived from Pten-/- fibroblasts migrated faster than on matrices from wild-type fibroblasts. Combined, these data demonstrate that PTEN loss in fibroblasts promotes extracellular matrix deposition and alignment independently from cancer cell presence, and this reorganization regulates cancer cell behavior. Importantly, stromal PTEN negatively correlated with collagen alignment and high mammographic density in human breast tissue, suggesting parallel function for PTEN in patients.


Retrospective study of gemcitabine plus S-1 versus gemcitabine alone in cases with unresectable advanced pancreatic cancer.
The aim of this study was to compare gemcitabine plus S-1 (GS) combination chemotherapy to gemcitabine (GEM) monotherapy in cases with unresectable advanced pancreatic cancer. We retrospectively reviewed 107 consecutive patients with unresectable advanced pancreatic cancer who received GEM monotherapy or GS combination chemotherapy between 2004 and 2010. In 73 patients, GEM (1000 mg/m2) was administered intravenously on days 1, 8 and 15, repeated every four weeks. The GS regimen received by 34 patients consisted of intravenous GEM (1000 mg/m2) on days 1 and 8, combined with oral S-1 (40 mg/m2) twice daily on days 1-14, repeated every four weeks. Response rates in the GEM and GS groups (6.8% versus 32.4%) varied significantly, as did disease control rates (28.8% versus 61.8%, respectively). There was a significant difference in median overall survival (206 versus 258 days) and median progression-free survival (86 versus 123 days) between the GEM and GS groups. Grade 3/4 toxicities in both groups were neutropenia (16.4% in GEM, 17.6% in GS), thrombocytopenia (1.3%, 2.9%), anorexia (1.3%, 0%), and diarrhea (1.3%, 0%). Retrospectively, GS combination therapy is feasible more effective than GEM monotherapy, and therefore should be considered in cases with unresectable advanced pancreatic cancer.


The influence of growth hormone (GH) substitution on patient-reported outcomes and cognitive functions in GH-deficient patients: a meta-analysis.
The influence of growth hormone (GH) replacement on patient-reported outcomes (i.e., quality of life, health status and well-being) and cognitive functioning in GH-deficient adults is controversial. We carried out a meta-analysis of clinical trials concerning the influence of GH substitution on patient-reported outcomes and cognitive functions (studies were selected from 1985 to 2004). The results of individual studies were combined in a series of meta-analyses using a random effects model. Effects of GH replacement in GH-deficient adults were compared to baseline and/or placebo. Fifteen studies on GH and patient-reported outcomes were included (830 patients, follow-up 3-50 months). Four of these studies also provided data on cognitive functions (85 patients, follow-up 6-12 months). Relative to baseline, GH treatment is found to have a large effect on patient-reported outcomes at 3 months, a medium effect at 6 months and a small effect at 12 months. With respect to the median treatment duration of 6 months placebo appears to be as effective as GH substitution. Cognitive functioning does not improve after 6 months of GH substitution, relative to baseline. This meta-analysis provides no evidence that GH improves patient-reported outcomes in GH-deficient patients. As the amount of cognitive data was too limited to allow for comparisons with placebo, from the present meta-analysis no conclusions can be drawn with respect to the impact of GH treatment on cognition.


Is antagonism of alpha3beta4 nicotinic receptors a strategy to reduce morphine dependence?
18-Methoxycoronaridine, a synthetic iboga alkaloid congener, has been previously shown to attenuate several signs of morphine withdrawal in rats. The recently discovered action of 18-methoxycoronaridine to block alpha3beta4 nicotinic receptors may be responsible for this effect. To test this hypothesis the effects of non-selective alpha3beta4 receptor antagonists, dextromethorphan, mecamylamine, bupropion, and their combinations, were assessed on of acute naltrexone-precipitated (1 mg/kg i.p.) morphine withdrawal in rats. Dextromethorphan (5-40 mg/kg, s.c.), mecamylamine (0.25-4 mg/kg, i.p.) and bupropion (10-30 mg/kg, i.p.) alone produced variable effects on signs of withdrawal. However, two low-dose combinations, i.e., dextromethorphan (5 mg/kg, s.c.) and mecamylamine (0.25 mg/kg, i.p.), mecamylamine (0.25 mg/kg, i.p.) and bupropion (10 mg/kg, i.p.) as well as the three-drug combination significantly attenuated diarrhea and weight loss; none of the agents administered alone had these effects. The results of the present study provide evidence that alpha3beta4 nicotinic receptors are involved in the expression of at least two signs of opioid withdrawal.


[Clinical study on the postburn change in the hypothalamus-pituitary-adrenal hormones in severely burned patients].
To investigate the postburn dynamic changes in the hypothalamus-pituitary-adrenal hormones in severely burned patients. Fifty burn patients were enrolled in the study. The plasma contents of total GC (cortisol), ACTH and aldosterone (ALDO) and urinary contents of 17-OHO and 17-KS were determined with radio-immunological assay (RIA) method after burn injury to compare with the normal values which were well established clinically. The postburn plasma and urinary contents of the above indices were increased evidently with two peak values in shock and infectious stages, whilst the majority of he indices were lower than the normal values after 6 postburn weeks (PBWs). The values of these hormones were the lowest in dying patients. On the other hand, the values approached normal levels in those patients whose burn wounds were healing. Increases of the plasma and urinary levels of hypothalamus-pituitary -adrenal hormones in severely burned patients were constantly seen. Burn shock and infection seemed to be the two major factors in inducing postburn stress reaction in burn victims. Abrupt decrease of the hormone levels in plasma and or urine indicated adrenal failure predicting a poor prognosis of the burn patients.


On the importance of relative salience: comparing overt selection behavior of single versus simultaneously presented stimuli.
The goal of the current study was to investigate time-dependent effects of the number of targets presented and its interaction with stimulus salience on oculomotor selection performance. To this end, observers were asked to make a speeded eye movement to a target orientation singleton embedded in a homogeneous background of vertically oriented lines. In Experiment 1, either one or two physically identical targets were presented, whereas in Experiment 2 an additional orientation-based salience manipulation was performed. The results showed that the probability of a singleton being available for selection is reduced in the presence of an identical singleton (Experiment 1) and that this effect is modulated by the salience of the other singleton (Experiment 2). While the absolute orientation contrast of a target relative to the background contributed to the probability that it is available for selection, the crucial factor affecting selection was the relative salience between singletons. These findings are incompatible with a processing speed account, which highlights the importance of visibility and claims that a certain singleton identity has a unique speed with which it can be processed. In contrast, the finding that the number of targets presented affected a target's availability suggests an important role of the broader display context in determining oculomotor selection performance.


Detail-enhanced exposure fusion.
In a typical processing chain of image enhancement, an exposure fusion scheme can be used to synthesize a more detailed low dynamic range (LDR) image directly from a set of differently exposed LDR images, without generation of an intermediate high dynamic range image. In this brief, we introduce a new quadratic optimization-based method to extract fine details from a vector field. The new method extracts fine details from a set of differently exposed LDR images simultaneously. The extracted fine details are then added to an intermediate LDR image which is fused by simply using an existing exposure fusion scheme. With this, the proposed scheme can enhance fine details to produce sharper images.


Indicators for monitoring maternal and neonatal quality care: a systematic review.
Research and different organizations have proposed indicators to monitor the quality of maternal and child healthcare, such indicators are used for different purposes. To perform a systematic review of indicators for the central phases of the maternal and child healthcare continuum of care (pregnancy, childbirth, newborn care and postpartum). A search conducted using international repositories, national and international indicator sets, scientific articles published between 2012 and 2016, and grey literature. The eligibility criteria was documents in Spanish or English with indicators to monitor aspects of the continuum of care phases of interest. The identified indicators were characterized as follows: formula, justification, evidence level, pilot study, indicator type, phase of the continuum, intended organizational level of application, level of care, and income level of the countries. Selection was based on the characteristics associated with scientific soundness (formula, evidence level, and reliability). We identified 1791 indicators. Three hundred forty-six were duplicated, which resulted in 1445 indicators for analysis. Only 6.7% indicators exhibited all requirements for scientific soundness. The distribution by the classifying variables is clearly uneven, with a predominance of indicators for childbirth, hospital care and facility level. There is a broad choice of indicators for maternal and child healthcare. However, most indicators lack demonstrated scientific soundness and refer to particular continuum phases and levels within the healthcare system. Additional efforts are needed to identify good indicators for a comprehensive maternal and child healthcare monitoring system.


Finite element modeling of aponeurotomy: altered intramuscular myofascial force transmission yields complex sarcomere length distributions determining acute effects.
Finite element modeling of aponeurotomized rat extensor digitorium longus muscle was performed to investigate the acute effects of proximal aponeurotomy. The specific goal was to assess the changes in lengths of sarcomeres within aponeurotomized muscle and to explain how the intervention leads to alterations in muscle length-force characteristics. Major changes in muscle length-active force characteristics were shown for the aponeurotomized muscle modeled with (1) only a discontinuity in the proximal aponeurosis and (2) with additional discontinuities of the muscles' extracellular matrix (i.e., when both myotendinous and myofascial force transmission mechanisms are interfered with). After muscle lengthening, two cut ends of the aponeurosis were separated by a gap. After intervention (1), only active slack length increased (by approximately 0.9 mm) and limited reductions in muscle active force were found (e.g., muscle optimum force decreased by only 1%) After intervention (2) active slack increased further (by 1.2 mm) and optimum length as well (by 2.0 mm) shifted and the range between these lengths increased. In addition, muscle active force was reduced substantially (e.g., muscle optimum force decreased by 21%). The modeled tearing of the intramuscular connective tissue divides the muscle into a proximal and a distal population of muscle fibers. The altered force transmission was shown to lead to major sarcomere length distributions [not encountered in the intact muscle and after intervention (1)], with contrasting effects for the two muscle fiber populations: (a) Within the distal population (i.e. fibers with no myotendinous connection to the muscles' origin), sarcomeres were much shorter than within the proximal population (fibers with intact myotendinous junction at both ends). (b) Within the distal population, from proximal ends of muscle fibers to distal ends, the serial distribution of sarcomere lengths ranged from the lowest length to high lengths. In contrast within the proximal population, the direction of the distribution was reversed. Such differences in distribution of sarcomere lengths between the proximal and distal fiber populations explain the shifts in muscle active slack and optimal lengths. Muscle force reduction after intervention (2) is explained primarily by the short sarcomeres within the distal population. However, fiber stress distributions showed contribution of the majority of the sarcomeres to muscle force: myofascial force transmission prevents the sarcomeres from shortening to nonphysiological lengths. It is concluded that interfering with the intramuscular myofascial force transmission due to rupturing of the intramuscular connective tissue leads to a complex distribution of sarcomere lengths within the aponeurotomized muscle and this determines the acute effects of the intervention on muscle length-force characteristics rather than the intervention with the myotendinous force transmission after which the intervention was named. These results suggest that during surgery, but also postoperatively, major attention should be focused on the length and activity of aponeurotomized muscle, as changes in connective tissue tear depth will affect the acute effects of the intervention.


Effects of stress relaxation in beta-titanium cantilevers used in orthodontic mechanics.
This study evaluated the force decay and design shape changes caused by stress relaxation in two different orthodontic cantilever configurations. Eighty cantilevers made of 0.017 x 0.025-in beta-titanium wires were standardized in a passive position, using real scale templates, and randomly divided into two groups (n = 40): Type 1 and Type 2. Each group received a different design (Type 1 with three bends, and Type 2 with two bends), and both were divided in four subgroups (n = 10) according to the evaluation periods: G1 = 24h, G2 = 1 week, G3 = 4 weeks, and G4 = 8 weeks. Mechanical tests were performed immediately after preactivation and at the end of each period, to evaluate force decay. The cantilevers were also scanned and the angles of the bends were measured to assess shape changes. Cantilever forces decayed over time. Type 1 - G1 showed less force decay than Type 2 (10.83 cN vs 17.87 cN). Type 1 cantilevers showed significant force decay only when G4 was compared to G1 (9.05 cN), G2 (11.73 cN), and G3 (9.78 cN). Type 2 cantilevers presented differences when G1 was compared to G2 (9.57 cN) and G3 (7.89 cN). Regarding to the cantilever angle closest to the bracket insertion, Type 1 cantilevers showed significant decrease for G2 (1.58°) and G4 (1.52°). Cantilevers' design and proximity of the bends influenced force decay pattern overtime. Type 1 cantilevers presented more stable design at the first weeks than Type 2.


Prognosis and risk stratification in young papillary thyroid carcinoma patients.
Controversies remain regarding to the therapeutic methods of papillary thyroid cancer (PTC) in young patients. TNM staging and other risk evaluation system are not perfectly applicable for all young PTC patients in view of disease outcome. The aims of this study are to identify the clinical presentations, prognostic factors and risk analysis methods. From January, 1977, to June, 2006, seventy-seven patients with primary PTC younger than 20 years old at Chang Gung Medical Center in Taiwan were enrolled in this retrospective study. The patients were classified as disease-free or non-disease-free according to presence or absence of distant metastases or local recurrence at the end of follow-up. Clinical data of these patients were analyzed and compared. The average follow-up period was 10.3 years. Two patients died of PTC during the follow-up period; one died of brain metastasis, and one died of airway obstruction. Patients undergoing total thyroidectomy, especially those with disease beyond the thyroid, had better outcomes than patients not undergoing total thyroidectomy (p = 0.003). Moreover, the DeGroot clinical classification system was a better predictor of prognosis than TNM (p<0.001 vs p = 0.007). Our results suggest that prognosis for PTC is not worse in younger patients. However, patients who had undergone total thyroidectomy might have a better prognosis. Clinical classification is a good alternative classification system for predicting disease outcome in young PTC patients. Patients with confined intrathyroid lesion (<or=T2, N0, M0) may be regarded "low risk" PTC patients.


Plasma very low density lipoproteins from male rats fed casein or soybean protein diets: a comparison of fatty acid composition and influence on prostanoid production.
In studies with male rats fed for 4 wk semipurified diets containing olive oil and casein or soybean protein, protein-dependent effects were observed in the fatty acid composition of the VLDL lipids, especially with regard to the pattern of polyunsaturated fatty acids. Compared with VLDL from rats fed soybean protein diet (S-VLDL), VLDL from casein-fed rats (C-VLDL) contained a greater level of oleic acid, and a reduced level of linoleic acid and arachidonic acid, in the phosphatidylcholine fraction. The proportion of 5,8,11-eicosatrienoic acid, 20:3 (n-9), varied among the different lipid classes. The highest concentration of this fatty acid (13% by weight of total fatty acids) was observed in the phosphatidylinositol fraction of C-VLDL. The level of linoleic acid was approximately halved in the triacylglycerol and cholesteryl ester fractions of C-VLDL compared with S-VLDL. When mouse peritoneal macrophages were incubated with different concentrations of S-VLDL, a saturable accumulation of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TXB2) was observed in the cell medium. In contrast, very low levels of 6-keto-PGF1 alpha and TXB2 were observed in the cell medium of macrophages incubated with C-VLDL at different lipoprotein concentrations, suggesting that the composition of VLDL may play an important role in relation to cellular prostanoid metabolism.


Computed tomography is important in assessing resectability of pancreatic carcinoma, even after ultrasonographic demonstration of the tumour.
In Finland pancreatic tumour is often detected initially on ultrasonography (US), which is widely used as a primary examination in patients who have epigastric pain or are jaundiced. This retrospective study was performed to investigate whether computed tomography (CT) provided any essential substantial staging information to US in patients, whose primary tumour was detected in US. Both US and CT had been performed in 102 pancreatic carcinoma patients. US, being performed always prior to CT, detected the pancreatic tumour in 73 patients (sensitivity 72%). CT detected pancreatic tumour in 65 of these 73 patients (89%). US demonstrated the tumour to be unresectable in 22 patients (30%). CT demonstrated the tumour as unresectable in the same 22 patients, but also in additional 20 patients (overall 42 patients = 58%, P less than 0.001 as compared to US). Three of these 20 patients underwent biliary bypass, but in 17 patients laparotomy was considered unnecessary (including the six patients who underwent merely exploratory laparotomy). It was estimated, that the 51 CT examinations, performed in patients in whom the pancreatic tumour was detected resectable on US, with overall costs of about FIM 137,700, might obviate laparotomy in 17 patients, with operative costs of about FIM 255,000. Thus, CT appears to provide essential substantial information to US about the resectability of pancreatic carcinoma, and CT can be considered a very important preoperative examination from both medical and economical point of view in the patients whose pancreatic tumour has been demonstrated by US.


Size-controlled synthesis of granular polyphosphate nanoparticles at physiologic salt concentrations for blood clotting.
Size-controlled granular polyphosphate (PolyP) nanoparticles were synthesized by precipitation in aqueous solutions containing physiological concentrations of calcium and magnesium. We demonstrate using dynamic light scattering (DLS) that the solubility is correlated inversely with PolyP chain length, with very long chain PolyP (PolyP1000+, more than 1000 repeating units) normally found in prokaryotes precipitating much more robustly than shorter chains like those found in human platelet dense granules (PolyP80, range 76-84 repeating units). It is believed that the precipitation of PolyP is a reversible process involving calcium coordination to phosphate monomers in the polymer chain. The particles are stable in aqueous buffer and albumin suspensions on time scales roughly equivalent to catastrophic bleeding events. Transmission electron microscopy images demonstrate that the PolyP nanoparticles are spherical and uniformly electron dense, with a particle diameter of 200-250 nm, closely resembling the content of acidocalcisomes. X-ray elemental analysis further reveals that the P/Ca ratio is 67:32. The granular nanoparticles also manifest promising procoagulant effects, as measured by in vitro clotting tests assaying contact pathway activity.


Finite mode analysis through harmonic waveguides
The mode analysis of signals in a multimodal shallow harmonic waveguide whose eigenfrequencies are equally spaced and finite can be performed by an optoelectronic device, of which the optical part uses the guide to sample the wave field at a number of sensors along its axis and the electronic part computes their fast Fourier transform. We illustrate this process with the Kravchuk transform.


Tissue-Specific Regulation of Plastid Protein Import via Transit-Peptide Motifs.
Plastids differentiate into various functional types (chloroplasts, leucoplasts, chromoplasts, etc.) that have distinct proteomes depending on the specific tissue. Most plastid proteins are encoded by the nuclear genome, synthesized as higher molecular mass preproteins with an N-terminal transit peptide, and then posttranslationally imported from the cytosol. Evidence for tissue-specific regulation of import into plastids, and subsequent modulation of plastid proteomes, has been lacking. We quantified protein import into isolated pea (Pisum sativum) leaf chloroplasts and root leucoplasts and identified two transit-peptide motifs that specifically enhance preprotein import into root leucoplasts. Using a plastid preprotein expressed in both leaves and roots of stable transgenic plants, we showed that losing one of the leucoplast motifs interfered with its function in root leucoplasts but had no effect on its function in leaf chloroplasts. We assembled a list of all Arabidopsis (Arabid opsis thaliana) plastid preproteins encoded by recently duplicated genes and show that, within a duplicated preprotein pair, the isoform bearing the leucoplast motif usually has greater root protein abundance. Our findings represent a clear demonstration of tissue-specific regulation of organelle protein import and suggest that it operates by selective evolutionary retention of transit-peptide motifs, which enhances import into specific plastid types.