The distribution of estrogen receptor-beta mRNA in forebrain regions of the estrogen receptor-alpha knockout mouse.
Neurons in the hypothalamus of estrogen receptor alpha-knockout (ER alphaKO) mice have been shown to concentrate radiolabeled estrogen and estrogen treatment regulates the expression of progesterone receptor mRNA. The purpose of the present study was to utilize in situ hybridization histochemistry to determine the anatomical distribution of ER beta mRNA in ER alphaKO mouse forebrain. The results of these studies revealed an extensive distribution of ER beta mRNA in the hypothalamic regions including medial preoptic area, suprachiasmatic nucleus, paraventricular nucleus, dorsomedial nucleus, medial tuberal nucleus, and the premammillary nuclei. Additional labeled perikarya were also detected in the glomerular layer of the olfactory bulb; tenia tecta; anterior septum; bed nucleus of the stria terminalis; medial, basolateral and cortical nuclei of the amygdala; cerebral and entorhinal cortex; the septohippocampal nucleus; Ammon's horn of the hippocampus and the dorsal raphe. The results of these in situ hybridization histochemical studies have provided novel information about the distribution of ER beta mRNA in the ER alphaKO mouse forebrain. In addition, these morphological data provides evidence that estrogen may exert its actions in the ER alphaKO mouse brain via ER beta and thereby maintain organizational and activational effects.


Orexin and natural reward: feeding, maternal, and male sexual behavior.
Orexin, also known as hypocretin, is a hypothalamic neuropeptide important for mediation of arousal and sleep as well as feeding and energy homeostasis. Recent studies have indicated that orexin also plays a key role regulating motivation and reward associated with food intake and with drugs of abuse. Based on those findings, it has been hypothesized that orexin is involved in control of other natural reward behaviors. This review will summarize studies that examine the role of orexin in motivation and reward associated with food intake, maternal behavior, and male sexual behavior. In particular for sexual behavior in male rats, we have recently shown that orexin cell-specific lesions do not impair sexual performance and motivation but disrupt conditioned responses associated with sexual reward.


Defective Gpsm2/Gαi3 signalling disrupts stereocilia development and growth cone actin dynamics in Chudley-McCullough syndrome.
Mutations in GPSM2 cause Chudley-McCullough syndrome (CMCS), an autosomal recessive neurological disorder characterized by early-onset sensorineural deafness and brain anomalies. Here, we show that mutation of the mouse orthologue of GPSM2 affects actin-rich stereocilia elongation in auditory and vestibular hair cells, causing deafness and balance defects. The G-protein subunit Gαi3, a well-documented partner of Gpsm2, participates in the elongation process, and its absence also causes hearing deficits. We show that Gpsm2 defines an ∼200 nm nanodomain at the tips of stereocilia and this localization requires the presence of Gαi3, myosin 15 and whirlin. Using single-molecule tracking, we report that loss of Gpsm2 leads to decreased outgrowth and a disruption of actin dynamics in neuronal growth cones. Our results elucidate the aetiology of CMCS and highlight a new molecular role for Gpsm2/Gαi3 in the regulation of actin dynamics in epithelial and neuronal tissues.


Work environmental factors and retention of nurses.
Perceptions of the work environment were studied among acute care nurses working in a large county hospital who left their units during an 18-month period, compared to those who stayed. Analysis using Moos' work environment subscales suggests that the nurses who remained in their units perceived less work pressure and had greater perception of peer cohesion, supervisor support, and autonomy than nurses who left. Moos' Work Environment Scale suggests that a supportive work environment enables nurses to provide quality patient care, enhance their own self-esteem, increase job satisfaction, and provide cost savings to their employers. Such an environment promotes retention of skilled, caring, knowledgeable, and experienced nurses who provide better patient care with fewer complications, and reduces the economic and social costs of healthcare for both providers and consumers.


Catheter ablation of atrial fibrillation-A key role in heart failure therapy?
Atrial fibrillation (AF) and heart failure (HF) are epidemic cardiac diseases and are often detected in the same patient. Recent evidence suggests that this is not a mere coincidence but that the strategy of AF treatment may impact HF development. This review comprehensively summarizes current trial data on rhythm and rate control strategies in atrial fibrillation with a special focus on catheter ablation of AF in HF patients. For a long time, rate and rhythm control strategies for AF have been regarded as equal regarding long term mortality. Decision making has been based on the symptoms of patients. Current trials, however, show that the treatment strategy of AF and its effectiveness may significantly impact survival of HF patients. The benefits of rhythm control in HF patients may have been masked by side effects of antiarrhythmic drugs. If rhythm control, however, is achieved by catheter ablation, a reduction of HF related mortality can be observed. As catheter ablation of AF may reduce mortality in HF patients, AF ablation should be preferred over medical treatment in HF patients. In general, HF patients may profit most from rigorous AF treatment.


Tissue-wide expression profiling using cDNA subtraction and microarrays to identify tumor-specific genes.
With the objective of discovering novel putative intervention sites for anticancer therapy, we compared transcriptional profiles of breast cancer, lung squamous cell cancer (LSCC), lung adenocarcinoma (LAC), and renal cell cancer (RCC). Each of these tumor types still needs improvement in medical treatment. Our intention was to search for genes not only highly expressed in the majority of patient samples but which also exhibit very low or even absence of expression in a comprehensive panel of 16 critical (vital) normal tissues. To achieve this goal, we combined two powerful technologies, PCR-based cDNA subtraction and cDNA microarrays. Seven subtractive libraries consisting of approximately 9250 clones were established and enriched for tumor-specific transcripts. These clones, together with approximately 1750 additional tumor-relevant genes, were used for cDNA microarray preparation. Hybridizations were performed using a pool of 16 critical normal tissues as a reference in all experiments. In total, we analyzed 20 samples of breast cancer, 11 of LSCC, 11 of LAC, and 8 of RCC. To select for genes with low or even no expression in normal tissues, expression profiles of 22 different normal tissues were additionally analyzed. Importantly, this tissue-wide expression profiling allowed us to eliminate genes, which exhibit also high expression in normal tissues. Similarly, expression signatures of genes, which are derived from infiltrating cells of the immune system, were eliminated as well. Cluster analysis resulted in the identification of 527 expressed sequence tags specifically up-regulated in these tumors. Gene-wise hierarchical clustering of these clones clearly separated the different tumor types with RCC exhibiting the most homogeneous and LAC the most diverse expression profile. In addition to already known tumor-associated genes, the majority of identified genes have not yet been brought into context with tumorigenesis such as genes involved in bone matrix mineralization (OSN, OPN, and OSF-2) in lung, breast, and kidney cancer or genes controlling Ca(2+) homeostasis (RCN1,CALCA, S100 protein family). EGLN3, which recently has been shown to be involved in regulation of hypoxia-inducible factor, was found to be highly up-regulated in all RCCs and in half of the LSCCs analyzed. Furthermore, 42 genes, the expression level of which correlated with the overall survival of breast cancer patients, were identified. The gene dendogram clearly separates two groups of genes, those up-regulated such as cyclin B1, TGF-beta 3, B-Myb, Erg2, VCAM-1, and CD44 and those down-regulated such as MIG-6, Esp15, and CAK in patients with short survival time.


Knowledge, beliefs and attitudes on leprosy in Iloilo City Proper, Philippines.
This study attempts to find out the prevailing knowledge and beliefs in Iloilo City, Philippines regarding leprosy, its causation, mode of transmission, and care. Attitudes of people towards Hansenites and their offsprings are also looked into. Qualitative data are obtained from seven keypersons in the locality who were interviewed in-depth using the unstructured interview guide. Quantitative data are furnished by 100 household heads who were randomly chosen and by 70 senior student-nurses enrolled in the six colleges of nursing in the same city using an interview schedule and questionnaire respectively. Results reveal that 90% of the household heads and 45% of the students have inadequate knowledge on leprosy. None of the household heads and only two students have highly adequate knowledge pertaining to this disease. Leprosy is believed by both the household heads and students to be brought about by as well as supernatural causes. A great majority of the household heads (94%) and students (79%) attribute the cause of leprosy to germs. Blood predilection has been cited by the next highest proportion of both groups of respondents. The third highest proportion of the households heads attribute the cause of the illness to God's will, while among the students, the cause of this disease is believed to be spontaneous. The majority of household heads (94%) and students (95%) believe that skin to skin contact is the most possible mode of transmitting the disease.


Effects of bronchial blockers on one-lung ventilation in general anesthesia: A randomized controlled trail.
Double-lumen bronchial tubes (DLBT) and bronchial blockers (BB) are commonly used in the anesthesia for clinical thoracic surgery. But there are few systematic clinical comparisons between them. In this study, the effects of BB and DLBT on one-lung ventilation (OLV) are studied. The 200 patients with thoracic tuberculosis undergoing thoracic surgery, were randomly assigned to group A (DLBT) and group B (BB). Intubation time, hemodynamic changes (mean arterial pressure [MAP], heart rate [HR]), and arterial blood gas indicators (arterial partial pressure of carbon dioxide [PaCO2], arterial partial pressure of oxygen [PaO2], airway plateau pressure [Pplat], and airway peak pressure [Ppeak]) at 4 time points were recorded. Complications such as hoarseness, pulmonary infection, pharyngalgia, and surgical success rate were also evaluated postoperatively. Intubation times were shorter in group B. Both MAP and HR in group A were significantly higher 1 minute after intubation than before, but also higher than those in group B. PaO2 levels were lower in both groups during (OLV) than immediately after anesthesia and after two-lung ventilation (TLV), with PaO2 being lower after 60 minutes of OLV than after 20 minutes of OLV. Furthermore, at both points during OLV, PaO2 was lower in group A than in group B. No significant differences in PaCO2 were found between the 2 groups. Ppeak and Pplat were increased in both groups during OLV, with both being higher in group A than in group B. The incidence of postoperative hoarseness, pulmonary infection, and pharyngalgia were lower in group B. There was no significant difference in the success rate of operation between the 2 groups. Compare with using DLBT, implementation of BB in general anesthesia has less impact on hemodynamics, PaO2 and airway pressures, and achieves lower incidence of postoperative complication.


Expression and immunogenicity of novel subunit enterovirus 71 VP1 antigens.
Hand, foot, and mouth disease (HFMD) is a common viral illness in young children. HFMD is caused by viruses belonging to the enterovirus genus of the picornavirus family. Recently, enterovirus 71 (EV71) has emerged as a virulent agent for HFMD with severe clinical outcomes. In the current report, we conducted a pilot antigen engineering study to optimize the expression and immunogenicity of subunit VP1 antigen for the design of EV71 vaccines. DNA immunization was adopted as a simple technical approach to test different designs of VP1 antigens without the need to express VP1 protein in vitro first. Our studies indicated that the expression and immunogenicity of VP1 protein can be improved with alternated VP1 antigen designs. Data presented in the current report revealed novel pathways to optimize the design of VP1 antigen-based EV71 vaccines.


Identifying temporal and causal contributions of neural processes underlying the Implicit Association Test (IAT).
The Implicit Association Test (IAT) is a popular behavioral measure that assesses the associative strength between outgroup members and stereotypical and counterstereotypical traits. Less is known, however, about the degree to which the IAT reflects automatic processing. Two studies examined automatic processing contributions to a gender-IAT using a data driven, social neuroscience approach. Performance on congruent (e.g., categorizing male names with synonyms of strength) and incongruent (e.g., categorizing female names with synonyms of strength) IAT blocks were separately analyzed using EEG (event-related potentials, or ERPs, and coherence; Study 1) and lesion (Study 2) methodologies. Compared to incongruent blocks, performance on congruent IAT blocks was associated with more positive ERPs that manifested in frontal and occipital regions at automatic processing speeds, occipital regions at more controlled processing speeds and was compromised by volume loss in the anterior temporal lobe (ATL), insula and medial PFC. Performance on incongruent blocks was associated with volume loss in supplementary motor areas, cingulate gyrus and a region in medial PFC similar to that found for congruent blocks. Greater coherence was found between frontal and occipital regions to the extent individuals exhibited more bias. This suggests there are separable neural contributions to congruent and incongruent blocks of the IAT but there is also a surprising amount of overlap. Given the temporal and regional neural distinctions, these results provide converging evidence that stereotypic associative strength assessed by the IAT indexes automatic processing to a degree.


A clinical review of the investigation and management of carcinoma of unknown primary in a single cancer network.
Carcinoma of unknown primary (CUP) is a common encounter in oncological practice and represents 2.0-6.0% of all invasive malignancies. Evidence to support particular therapeutic strategies in this patient population is scarce, and empirical therapies are frequently derived from research on patients where the primary tumour site is known. This retrospective study reviewed the management of all patients recorded to have a diagnosis of CUP in a single cancer centre over a period of 12 months. Health records were reviewed documenting the CUP subtype, the investigations carried out both in the referring cancer unit and subsequently at the cancer centre and the recommended treatment (type and regimen), together with survival. The outcomes were examined in respect to a number of prognostic factors. Statistical tests were considered significant at P < 0.05. One hundred and sixty-six patients were recorded to have a diagnosis of CUP, representing 3.7% of all referrals to the cancer centre. The median age of patients was 68 years (range 32-94 years), and 52.0% were women. The three most common CUP subgroups were CUP-liver/multiple sites (25.0%), CUP-bone (21.0%) and CUP-brain (16.0%). The remaining subgroups occurred at frequencies of less than 10% each. Histological confirmation was only obtained in 55.0% of cases. Even within a single subtype, 41 patients with CUP-liver/multiple sites underwent a total of 19 different investigations before any treatment being given. Forty-seven (28.0%) patients received radiotherapy, 30 (18.0%) received chemotherapy and 58 (35.0%) received supportive care alone. Nine different 5-fluorouracil-containing regimens were used in 11 patients treated with chemotherapy for CUP-liver. The overall median survival for all patients was 4.0 months. Survival was better in patients with a good performance status (0-1) and absent liver metastases (median survival 15.0 months; 95% confidence interval 8.0-22.1) and those who received chemotherapy (median survival 13.0 months; 95% confidence interval 7.4-18.6). Multivariate analysis confirmed female gender (P = 0.006), a good performance status (0/1) (P < 0.0001) and absent liver metastases (P = 0.002) as favourable prognostic indicators. The appropriate management of patients with CUP is unclear and this study revealed a high degree of variation in clinical practice. This area is in urgent need of clinical research to ensure that the treatment of CUP is evidence based. Until such time, clinical recommendations are suggested for the investigation and treatment of such patients. Therapeutic progress will be facilitated by designating a clinical lead for CUP in each clinical network.


Split down the middle: studying arbuscular mycorrhizal and ectomycorrhizal symbioses using split-root assays.
Most land plants symbiotically interact with soil-borne fungi to ensure nutrient acquisition and tolerance to various environmental stressors. Among these symbioses, arbuscular mycorrhizal and ectomycorrhizal associations can be found in a large proportion of plants, including many crops. Split-root assays are widely used in plant research to study local and systemic signaling responses triggered by local treatments, including nutrient availability, interaction with soil microbes, or abiotic stresses. However, split-root approaches have only been occasionally used to tackle these questions with regard to mycorrhizal symbioses. This review compiles and discusses split-root assays developed to study arbuscular mycorrhizal and ectomycorrhizal symbioses, with a particular emphasis on colonization by multiple beneficial symbionts, systemic resistance induced by mycorrhizal fungi, water and nutrient transport from fungi to colonized plants, and host photosynthate allocation from the host to fungal symbionts. In addition, we highlight how the use of split-root assays could result in a better understanding of mycorrhizal symbioses, particularly for a broader range of essential nutrients, and for multipartite interactions.


The Crucial Roles of Intermediate Metabolites in Cancer.
Metabolic alteration, one of the hallmarks of cancer cells, is important for cancer initiation and development. To support their rapid growth, cancer cells alter their metabolism so as to obtain the necessary energy and building blocks for biosynthetic pathways, as well as to adjust their redox balance. Once thought to be merely byproducts of metabolic pathways, intermediate metabolites are now known to mediate epigenetic modifications and protein post-transcriptional modifications (PTM), as well as connect cellular metabolism with signal transduction. Consequently, they can affect a myriad of processes, including proliferation, apoptosis, and immunity. In this review, we summarize multiple representative metabolites involved in glycolysis, the pentose phosphate pathway (PPP), the tricarboxylic acid (TCA) cycle, lipid synthesis, ketogenesis, methionine metabolism, glutamine metabolism, and tryptophan metabolism, focusing on their roles in chromatin and protein modifications and as signal-transducing messengers.


3D Bioprinting Mesenchymal Stem Cell-Derived Neural Tissues Using a Fibrin-Based Bioink.
Current treatments for neurodegenerative diseases aim to alleviate the symptoms experienced by patients; however, these treatments do not cure the disease nor prevent further degeneration. Improvements in current disease-modeling and drug-development practices could accelerate effective treatments for neurological diseases. To that end, 3D bioprinting has gained significant attention for engineering tissues in a rapid and reproducible fashion. Additionally, using patient-derived stem cells, which can be reprogrammed to neural-like cells, could generate personalized neural tissues. Here, adipose tissue-derived mesenchymal stem cells (MSCs) were bioprinted using a fibrin-based bioink and the microfluidic RX1 bioprinter. These tissues were cultured for 12 days in the presence of SB431542 (SB), LDN-193189 (LDN), purmorphamine (puro), fibroblast growth factor 8 (FGF8), fibroblast growth factor-basic (bFGF), and brain-derived neurotrophic factor (BDNF) to induce differentiation to dopaminergic neurons (DN). The constructs were analyzed for expression of neural markers, dopamine release, and electrophysiological activity. The cells expressed DN-specific and early neuronal markers (tyrosine hydroxylase (TH) and class III beta-tubulin (TUJ1), respectively) after 12 days of differentiation. Additionally, the tissues exhibited immature electrical signaling after treatment with potassium chloride (KCl). Overall, this work shows the potential of bioprinting engineered neural tissues from patient-derived MSCs, which could serve as an important tool for personalized disease models and drug-screening.


[State of microcirculation and the system of hemostasis in Sjögren's disease, Sjögren's syndrome and chronic parenchymatous parotitis].
Microcirculation and hemocoagulation were examined in 88 patients with Sjögren's disease and Sjögren's syndrome (SD and SS) in 20 patients with chronic parenchymatous parotitis (CPP) without a "dry syndrome", and in 20 healthy donors by conjunctival angioscopy, capillaroscopy of the nail matrix, and histological study of the salivary glands. Hemostasis was explored with the use of 37 tests. SD and SS patients manifested significantly more pronounced microcirculatory disorders versus donors (P less than 0.001) and CPP patients (P less than 0.001). In patients with hypergammaglobulinemic purpura, microcirculatory disorders were found to be enhanced (P less than 0.05). An indirect relationship between these disorders and the degree of lacrimation lowering was established. Intravascular disturbances increased as the process activity rose and diminished under the effect of prednisolone therapy. It is assumed that microcirculatory and hemocoagulation disorders play an important role in the pathogenesis of SD and SS.


Persecutory delusions and the perception of trustworthiness in unfamiliar faces in schizophrenia.
Persecutory delusions, a common symptom of schizophrenia, involve a disruption in the way that patients determine the intentions of others and especially their trustworthiness. However, it is unclear to what extent general preference affects trustworthiness judgments in patients with schizophrenia and how that relates to paranoid symptomology. Patients with schizophrenia and control subjects rated unfamiliar faces for trustworthiness and attractiveness (as a proxy for preference). The results demonstrate that patients do not show an overall difference in their trustworthiness ratings of unfamiliar faces. However, they do show a significant reduction in the correlation between trustworthiness and other indicators of preference, in this case, attractiveness judgments. The level of persecutory delusions is associated with this effect, such that patients with low levels of delusions show correlations near that of normal controls and high levels of persecutory delusions are related to a reduced trust/attractiveness correlation. These results suggest that patients with schizophrenia suffering from persecutory delusions rely less on normative social cues when making interpersonal judgments. Such findings underscore the importance of examining symptom-specific information when studying trust in patients with schizophrenia.


A review of the impact and potential of intermittent aeration on continuous flow nitrifying activated sludge.
Intermittent aeration of activated sludge plants (ASPs) is a potential strategy that may help deliver reduced operational costs while providing an adequate effluent quality. This review paper critically assesses the implications of temporary turning aeration offin continuous flow nitrifying ASPs, including impact on dissolved oxygen concentrations, process biology and operational parameters. The potential savings and pitfalls of the approach are further illustrated through an example scenario. Findings from this review indicate rapid dissolved oxygen depletion times of 1-60 minutes and a significant reduction of nitrification rates from 0.12 to less than 0.04 g NH4-N/g VSS/d. Further negative impacts include a potential increase in nitrous oxide emissions from 0.07% to 27% N2O-N per mole of NH4-N oxidized; enhanced filamentous bacteria growth; a noticeable increase in effluent turbidity developing within one hour of air supply interruption; and, if no mechanical mixing is in place, risk of mixed liquor suspended solids settling in the bioreactor within short times (23-53 min). However, the potential savings in terms of aeration costs could amount to 33%-45% if instrumentation adequacy and impact on process biology and carbon equivalent emissions are excluded from the economic analysis. Further research on the areas of nitrous oxide emissions and the use of hybrid systems to provide resilience and robustness to the intermittent operation of continuous flow nitrifying ASPs is recommended.


Barriers and Facilitators to Recurrent Preterm Birth Prevention among Low-Income Women: A Qualitative Study.
To examine patient perspectives on the experience of preterm birth (PTB) and recommended PTB prevention strategies, focusing on barriers to and facilitators of PTB prevention among low-income women. This is an observational study using qualitative methodology to investigate barriers to and facilitators of recurrent PTB prevention among low-income pregnant and postpartum women. Participants were either (1) postpartum from an initial spontaneous PTB, (2) pregnant and receiving 17-α-hydroxyprogesterone caproate (17P), or (3) pregnant or postpartum and declined/discontinued 17P. Participants completed individual interviews, and transcripts were analyzed using modified grounded theory techniques. Of 33 participants, the majority identified as non-Hispanic black (64%) or Hispanic (27%). Four facilitator themes included patient-centered environment, informed choice, social network, and motivation for a healthy family. Barriers included competing demands, resources, skepticism, and normalization. Three considerations, termed subjective influencers, could support women's decisions to use or decline 17P, including personal beliefs about one's body, the role of the fetus, and beliefs on interventionism. The facilitators and barriers identified herein offer insight into the lived experiences of women at a risk of recurrent PTB. Future programs aimed at reducing PTB disparities may benefit from addressing low-income minority women's structural and social determinants of PTB prevention.


Experimental evolution of prepared learning.
Animals learn some things more easily than others. To explain this so-called prepared learning, investigators commonly appeal to the evolutionary history of stimulus-consequence relationships experienced by a population or species. We offer a simple model that formalizes this long-standing hypothesis. The key variable in our model is the statistical reliability of the association between stimulus, action, and consequence. We use experimental evolution to test this hypothesis in populations of Drosophila. We systematically manipulated the reliability of two types of experience (the pairing of the aversive chemical quinine with color or with odor). Following 40 generations of evolution, data from learning assays support our basic prediction: Changes in learning abilities track the reliability of associations during a population's selective history. In populations where, for example, quinine-color pairings were unreliable but quinine-odor pairings were reliable, we find increased sensitivity to learning the quinine-odor experience and reduced sensitivity to learning quinine-color. To the best of our knowledge this is the first experimental demonstration of the evolution of prepared learning.


Impaired GABA neuronal response to acute benzodiazepine administration in panic disorder.
Disturbances in the metabolism of the brain amino acid transmitter gamma-aminobutyric acid (GABA) may contribute to the pathophysiology of human anxiety disorders. Animal studies indicate that deletions or reductions in the expression of the gene for the GABA synthetic enzyme, glutamate decarboxylase 65 (GAD(65)), reduce basal cortical GABA levels or stress-induced release of GABA in the cerebral cortex and increase fear behaviors. Complementing these findings, the authors recently observed lower than normal cortical GABA levels in patients with panic disorder. In the current study, the authors tested the hypothesis that panic disorder patients have a deficient GABA neuronal response to benzodiazepine (clonazepam) administration. In a parallel-group, repeated-measures design, occipital cortex GABA responses to acute oral, open-label benzodiazepine administration were tested in 10 panic disorder patients and nine healthy comparison subjects. Occipital cortex total GABA levels were measured before and after medication administration by means of a novel proton magnetic resonance spectroscopic technique. Panic disorder patients had a deficient GABA neuronal response (blunted reduction of occipital cortex GABA level) to acute benzodiazepine administration, compared to the healthy subjects, who exhibited a significant decrease in occipital cortex GABA levels after this intervention. The patients also appeared to have persistently low occipital cortex GABA after chronic benzodiazepine treatment. Overall, these data are consistent with the hypothesis that a trait-like abnormality in GABA neuronal function contributes to the pathogenesis of human panic disorder. The data raise the possibility that GAD(65) enzyme dysfunction could be a pathogenic factor in panic disorder.


SplitStreams: A Visual Metaphor for Evolving Hierarchies.
The visualization of hierarchically structured data over time is an ongoing challenge and several approaches exist trying to solve it. Techniques such as animated or juxtaposed tree visualizations are not capable of providing a good overview of the time series and lack expressiveness in conveying changes over time. Nested streamgraphs provide a better understanding of the data evolution, but lack the clear outline of hierarchical structures at a given timestep. Furthermore, these approaches are often limited to static hierarchies or exclude complex hierarchical changes in the data, limiting their use cases. We propose a novel visual metaphor capable of providing a static overview of all hierarchical changes over time, as well as clearly outlining the hierarchical structure at each individual time step. Our method allows for smooth transitions between treemaps and nested streamgraphs, enabling the exploration of the trade-off between dynamic behavior and hierarchical structure. As our technique handles topological changes of all types, it is suitable for a wide range of applications. We demonstrate the utility of our method on several use cases, evaluate it with a user study, and provide its full source code.


Determinants of early readmission after hospitalization for heart failure.
Determination of factors increasing the likelihood of early readmission after hospitalization for heart failure (HF) is fundamental for identifying potential targets for intervention. Thus, we studied the characteristics of patients readmitted within 7 and 30 days after hospitalization for HF in Alberta, Canada. Using hospital discharge abstract data, we followed patients with incident HF discharged from April 2004-March 2012 and determined their readmission status within 7 and 30 days after an index hospitalization. Logistic regression was used to determine variables associated with readmission. Of 18,590 patients with HF (49.8% women; mean age 76.4 years), 5.6% were readmitted within 7 days and 18% were readmitted within 30 days. Readmission rates within 7 and 30 days increased significantly with age. Seven-day all-cause readmissions were associated with history of kidney disease (adjusted odds ratio [aOR], 1.28; 95% confidence interval [CI], 1.08-1.53), and 30-day all-cause readmissions were associated with cancer, pulmonary, liver, and kidney disease. Discharge with home care services at the time of discharge was a risk factor for readmission within 7 days (aOR, 1.26; 95% CI, 1.07-1.49) and 30 days (aOR, 1.23; 95% CI, 1.11-1.35). Discharge from a hospital with HF services was associated with lower readmission at both 7 days (aOR, 0.65; 95% CI, 0.57-0.74) and 30 days (aOR, 0.71; 95% CI, 0.65-0.77). Several factors were associated with increased risk of readmission, whereas patients discharged from hospitals with HF services had a lower risk of readmission within 7 and 30 days of discharge. The interaction of provision of home care and higher early readmission deserves further study.


Dual electrospray ionization source for confident generation of accurate mass tags using liquid chromatography Fourier transform ion cyclotron resonance mass spectrometry.
Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) has rapidly established a prominent role in proteomics because of its unparalleled resolving power, sensitivity and ability to achieve high mass measurement accuracy (MMA) simultaneously. However, space-charge effects must be quantitatively, routinely, and confidently corrected because they are known to profoundly influence MMA. We argue that the most effective way to account for space-charge effects is to introduce an internal mass calibrant (IMC) using a dual electrospray ionization (ESI) source where the IMC is added from a separate ESI emitter. The major disadvantage of our initial dual ESI source to achieve high MMA, and arguably the only one, was the time required to switch between the analyte emitter and IMC emitter (i.e., >300 ms). While this "switching time" was acceptable for direct infusion experiments, it did not lend itself to high-throughput applications or when conducting on-line liquid separations. In this report, we completely redesigned the dual ESI source and demonstrate several key attributes. First, the new design allows for facile alignment of ESI emitters, undetectable vibration, and the ability to extend to multiple emitters. Second, the switching time was reduced to <50 ms, which allowed the analyte and IMC to be accumulated "simultaneously" in the external ion reservoir and injected as a single ion packet into the ion cyclotron resonance cell, eliminating the need for a separate accumulation and ion injection event for the IMC. Third, by using a high concentration of the IMC, the residence time on this emitter could be reduced to approximately 80 ms, allowing for more time spent accumulating analyte ions of significantly lower concentration. Fourth, multiplexed on-line separations can be carried out providing increased throughput. Specifically, the new dual ESI source has demonstrated its ability to produce a stable ion current over a 45-min time period at 7 T resulting in mass accuracies of 1.08 ppm +/- 0.11 ppm (mean +/- confidence interval of the mean at 95% confidence; N = 160). In addition, the analysis of a tryptic digest of apomyoglobin by nanoLC-dual ESI-FT-ICR afforded an average MMA of -1.09 versus -74.5 ppm for externally calibrated data. Furthermore, we demonstrate that the amplitude of a peptide being electrosprayed at 25 nM can be linearly increased, ultimately allowing for dynamic analyte/IMC abundance modulation. Finally, we demonstrate that this source can reliably be used for multiplexing measurements from two (eventually more) flow streams.


Effects of diabetes on rodent cardiac thyroid hormone receptor and isomyosin expression.
Previous studies show that diabetes induces marked transformations in cardiac myosin heavy chain (MHC) gene expression that are somehow linked to the cellular action of thyroid hormone 3,5,3'-triiodothyronine (T3). In this study, we tested the hypothesis that diabetes induces a reduced expression of thyroid hormone receptors (TRs), which are known to be important transcription factors interacting with thyroid response elements (TREs) in the promoter region of both alpha- and beta-MHC genes. Adult female rats were randomly assigned to either a normal control (NC) or diabetic (D) group. Three and/or six weeks after induction of diabetes via streptozotocin injection, the hearts of the animals were analyzed for MHC and TR mRNA isoforms expression, nuclear T3 binding, and nuclear extract interaction with a palindromic TRE. Results showed that diabetes induced significant alteration in alpha- and beta-MHC expression. Northern blot analyses indicated no diabetes-associated differences in TR isoform mRNA signals. Cardiac nuclear T3 binding studies suggested no differences in either the binding capacity or the equilibrium binding constant among the two groups, indicating no changes in either the number of nuclear TRs or their affinity for T3. Furthermore, gel mobility shift assays detected no difference between NC and D groups for cardiac nuclear extract binding to palindromic TRE. Collectively, these findings suggest that, whereas diabetes exerts a profound effect on cardiac isomyosin gene expression, the underlying mechanism, although dependent on factors linked to T3 function, does not involve alterations in TR expression.


[Actual standards for drinking water quality].
Actual recommendations concerning drinking water quality are presented in WHO "Guidelines for drinking water quality" published in 1992. Regulations which are obligatory in the European Union countries are published in Directive 80/778/EEC. In 1995 a proposal of a new Directive was elaborated. In Poland the regulations given in the disposition of MZiOS (Ministry of Health and Social Welfare)-Dz. U. nr 18 poz. 72 of 1977 with later changes-Dz.U. nr 35 poz. 205 of 1990 are obligatory. At present this disposition is under revision: Comparison of above mentioned regulations of EU and WHO with Polish regulations enables the following conclusions: The highest permissible concentrations of individual constituents dissolved in water listed in the Directive 80/778/EEC are in agreement with those given in the disposition of MZiOS of 1990. Parametric values in the draft project of the new Directive are in good accordance with those presented in the draft project of the disposition of MZiOS, except of the permissible concentrations of nitrites, cyanides, iron, acryloamide and vinyl chloride, which are in accordance with health criteria recommended by WHO. Only permissible lead concentration is in Poland twice greater than proposed by the WHO guidelines for drinking water. In Polish regulation the highest permissible concentrations are defined for greater number of substances including pesticides. In the author's opinion harmonization of the Polish regulations with the project of the new EU Directive should be performed after the EU project comes into force.


Group-based, individualized exercises can provide perceived bodily changes and strengthen aspects of self in individuals with MS: a qualitative interview study.
Background: Group-based physiotherapy is effective for individuals with MS; nevertheless individualization within groups is questioned and little is known regarding individuals´ experiences with individualization in small groups.Objective: We aimed to explore the short- and long-term experiences of individuals with MS participating in a 6-week, group-based, individualized physiotherapy-intervention.Methods: Within a randomized controlled trial (RCT), 25 in-depth interviews with a strategic sample of 13 people (9 women; age 25-79 years old; European Disability Status Scale (EDSS) 1-6.5) were conducted at weeks 7 and 30 using systematic text condensation, with dynamic systems theory and phenomenology as analytical frameworks.Results: The main categories were: 1) movement control, orientation and insights: Bodily improvements were associated with targeted exercises, specific adjustments by the physiotherapist, emotional engagement and re-access to activities; and 2) the individual within the group: Equal distributions of one-to-one interactions and attention were important for experiencing success. Less attention and improvements turned attention toward own disability. Physical changes felt particularly emotional short term, implying that individuals' feelings of ownership and control of body and movement, new views of themselves and changed affordances in daily life were involved.Conclusion: Equally distributed attention and engagement, targeted exercises and hands-on adjustments resulting in visible and perceived bodily changes were experienced as key factors of individualization in small groups.


Effects of chemical inhibition of histone deacetylase proteins in the growth and virulence of Macrophomina phaseolina (Tassi) Goid.
Chromatin remodeling enzymes are important "writers", "readers" and "erasers" of the epigenetic code. These proteins are responsible for the placement, recognition, and removal of molecular marks in histone tails that trigger structural and functional changes in chromatin. This is also the case for histone deacetylases (HDACs), i.e., enzymes that remove acetyl groups from histone tails, signaling heterochromatin formation. Chromatin remodeling is necessary for cell differentiation processes in eukaryotes, and fungal pathogenesis in plants includes many adaptations to cause disease. Macrophomina phaseolina (Tassi) Goid. is a nonspecific, necrotrophic ascomycete phytopathogen that causes charcoal root disease. M. phaseolina is a frequent and highly destructive pathogen in crops such as common beans (Phaseolus vulgaris L.), particularly under both water and high temperature stresses. Here, we evaluated the effects of the classical HDAC inhibitor trichostatin A (TSA) on M. phaseolinain vitro growth and virulence. During inhibition assays, the growth of M. phaseolina in solid media, as well as the size of the microsclerotia, were reduced (p<0.05), and the colony morphology was remarkably affected. Under greenhouse experiments, treatment with TSA reduced (p<0.05) fungal virulence in common bean cv. BAT 477. Tests of LIPK, MAC1 and PMK1 gene expression during the interaction of fungi with BAT 477 revealed noticeable deregulation. Our results provide additional evidence about the role of HATs and HDACs in important biological processes of M. phaseolina.


Examining the impact of surgical coaching on trainee physiologic response and basic skill acquisition.
We examined how problem-solving coaching impacts trainee skill acquisition and physiologic stress as well as how trainee sensitivity to feedback, known as self-monitoring ability, impacts coaching effectiveness. Medical students completed a pre-training demographics questionnaire, a 12-item self-monitoring ability scale (1 = always false, 5 = always true), and baseline FLS Task 5 with physiologic sensors. After watching a laparoscopic suturing instructional video, students practiced the task for 30 min, either with a surgical coach, or alone, depending on condition. The coach logged frequency of coaching behaviors according to a task-specific coaching script. Trainees then completed FLS Task 5 with physiologic sensors, a post-training questionnaire, and a 12-item coaching quality evaluation (1 = poor, 5 = very good). Twenty-four students (age 24.5 ± 1.4; 54% men; 58% MS4) participated in the study. All were fairly high self-monitors (3.8 ± 0.76). No differences in baseline suturing skills between the groups emerged. Improvement in the coaching group's suturing (N = 12; 285.0 ± 79.9) was significantly higher than the control group (N = 12; 200.9 ± 110.3). One measure of physiologic stress (rMSSD) was significantly higher in the coaching group. Trainees who received more coaching demonstrated larger improvements (r = 0.7, p < 0.05). Overall ,perceived quality of the coaching relationship was high (4.4 ± 0.6). There was no correlation between trainee self-monitoring ability and skill improvement. This work suggests that coaching may increase heart rate variability of trainees, indicating coping well with training. Trainee disposition toward feedback did not play a role in this relationship.


Utility of baseline 18FDG-PET/CT functional parameters in defining prognosis of primary mediastinal (thymic) large B-cell lymphoma.
The International Extranodal Lymphoma Study Group (IELSG) 26 study was designed to evaluate the role of (18)F-fluorodeoxyglucose (18FDG) positron emission tomography/computed tomography (PET/CT) in the management of primary mediastinal (thymic) large B-cell lymphoma (PMBCL). We examined the prognostic impact of functional PET parameters at diagnosis. Metabolic activity defined by the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) was measured on baseline 18FDG PET/CT following a standard protocol in a prospectively enrolled cohort of 103 PMBCL patients. All received combination chemoimmunotherapy with doxorubicin- and rituximab-based regimens; 93 had consolidation radiotherapy. Cutoff values were determined using the receiver-operating characteristic curve. At a median follow-up of 36 months, progression-free survival (PFS) and overall survival (OS) were 87% and 94%, respectively. In univariate analysis, elevated MTV and TLG were significantly associated with worse PFS and OS. Only TLG retained statistical significance for both OS (P = .001) and PFS (P < .001) in multivariate analysis. At 5 years, OS was 100% for patients with low TLG vs 80% for those with high TLG (P = .0001), whereas PFS was 99% vs 64%, respectively (P < .0001). TLG on baseline PET appeared to be a powerful predictor of PMBCL outcomes and warrants further validation as a biomarker. The IELSG 26 study was registered at www.clinicaltrials.gov as #NCT00944567.


The potential for probiotics to prevent bacterial vaginosis and preterm labor.
Infections of the urogenital tract in women represent a major burden on the quality of life of women and on the health care system of Canada and other countries. Complications arising from bacterial vaginosis (BV) include increased risk of sexually transmitted diseases including human immunodeficiency virus and elevated risk of preterm birth (PTB). Pharmaceutical interventions, such as antibiotics, have been suboptimally effective and have failed to reduce the incidence of PTB. The absence of lactobacilli in the vagina, a specific feature of BV, raises the question as to whether restoration of lactobacilli, by probiotic therapy, can restore the normal flora and improve the chances of having a healthy term pregnancy. The rationale for probiotic use in pregnant women is quite strong. Certain lactobacilli strains can safely colonize the vagina after oral and vaginal administration, displace and kill pathogens including Gardnerella vaginalis and Escherichia coli, and modulate the immune response to interfere with the inflammatory cascade that leads to PTB. Additional attributes of probiotics include their potential to degrade lipids and enhance cytokine levels, which promote embryo development. In a society that focuses on disease rather than health and drug therapy rather than natural preventive measures, it will take some effort to get remedies such as probiotics into mainstream care. Perhaps the escalating health care budgets and emergence of "superbugs" will provide the incentives to put in place clinical trials designed to evaluate how best to use the commensal organisms that, after all, make up more of our body than human cells, and without which none of us would survive.


Immediate postoperative pain: an atypical presentation of dropped gallstones after laparoscopic cholecystectomy.
Cholecystectomy is one of the most commonly performed surgical procedures in the United States. A common complication is dropped gallstones, and the diversity of their presentation poses a substantial diagnostic challenge. We report the case of a 58-year-old man presenting with chronic right upper quadrant hours status post cholecystectomy. Imaging demonstrated retained gallstones in the perihepatic space and symptoms remitted following their removal via laparoscopic operation. Gallstones are lost in roughly 1 in 40 cholecystectomies and are usually asymptomatic. The most common presentations are months or years status post cholecystectomy due to fistula, abscess, or sinus tract formation. We report this case hoping to bring light to a rare presentation for dropped gallstones and provide advice on the management of this common complication of cholecystectomy.


Gender differences in chewing discomfort in older South Koreans.
The purpose of this study was to identify gender differences in chewing discomfort among elderly Koreans. This study used data from 56 616 (weighted sample: 5 638 394) subjects aged over 65 years who participated in the 2011 Community Health Survey in Korea. Of them, 23 059 (weighted sample: 2 368 200, 42.0%) were men and 33 357 (weighted sample: 3 270 194, 58.0%) were women. Data were analysed using chi-square tests and hierarchical logistic regression analyses, with SPSS 20.0. Chewing discomfort was set as the dependent variable, and independent variables were divided into socio-economic factors (place of residence, age, education, monthly household income, basic living security stipend, private insurance, economic activity, living arrangements), general health factors (hypertension, diabetes) and oral health factors (tooth defects, denture use, subjective periodontal health status). A greater proportion of women (50.2%) than men (42.6%) exhibited chewing discomfort (P < 0.001). In men, place of residence, monthly household income, private health insurance, tooth defects and periodontal health were associated with chewing discomfort (P < 0.05). In women, age, education level, basic living security stipend and denture use were associated with chewing discomfort (P < 0.05). Elderly Korean women experience more severe chewing discomfort than their male counterparts. The factors associated with chewing also differ by gender.


Osteonecrosis of the hip: management in the 21st century.
Osteonecrosis of the femoral head is a progressive condition that often leads to collapse of the femoral head. The ultimate goal in the treatment for osteonecrosis of the hip is preservation of the femoral head. However, the condition is difficult to treat because it is associated with a number of different diseases, and the etiology and natural history of the condition have not been definitively determined. The delineation of new information regarding the etiology, pathogenesis, and natural history of osteonecrosis is ongoing. Core decompression, vascularized and nonvascularized bone grafting procedures, and arthroplasty procedures play an important role in treatment.


State of the science review: Advances in pain management in wounded service members over a decade at war.
The pain conditions and comorbidities experienced by injured service members and the challenge of pain management by the military medical system offer a unique opportunity to inform pain management and medical research. In this article, acute and chronic pain issues, current treatment options and limitations, as well as novel approaches to pain management are discussed within the context of combat casualty care, from the battlefield to hospitalization and rehabilitation. This review will also highlight the current pain management limitations that need to be addressed in future clinical and basic science research to improve care for our nation's injured service members.


Beyond cleaved small RNA targets: unraveling the complexity of plant RNA degradome data.
Degradation is essential for RNA maturation, turnover, and quality control. RNA degradome sequencing that integrates a modified 5'-rapid amplification of cDNA ends protocol with next-generation sequencing technologies is a high-throughput approach for profiling the 5'-end of uncapped RNA fragments on a genome-wide scale. The primary application of degradome sequencing has been to identify the truncated transcripts that result from endonucleolytic cleavage guided by microRNAs or small interfering RNAs. As many pathways are involved in RNA degradation, degradome data should contain other RNA species besides the cleavage remnants of small RNA targets. Nevertheless, no systematic approaches have been established to explore the hidden complexity of plant degradome. Through analyzing Arabidopsis and rice RNA degradome data, we recovered 11 short motifs adjacent to predominant and abundant uncapped 5'-ends. Uncapped ends associated with several of these short motifs were more prevalent than those targeted by most miRNA families especially in the 3' untranslated region of transcripts. Through genome-wide analysis, five motifs showed preferential accumulation of uncapped 5'-ends at the same position in Arabidopsis and rice. Moreover, the association of uncapped 5'-ends with a CA-repeat motif and a motif recognized by Pumilio/Fem-3 mRNA binding factor (PUF) proteins was also found in non-plant species, suggesting that common mechanisms are present across species. Based on these motifs, potential sources of RNA ends that constitute degradome data were proposed and further examined. The 5'-end of small nucleolar RNAs could be precisely captured by degradome sequencing. Position-specific enrichment of uncapped 5'-ends was seen upstream of motifs recognized by several RNA binding proteins especially for the binding site of PUF proteins. False uncapped 5'-ends produced from capped transcripts through non-specific PCR amplification were common artifacts among degradome datasets. The complexity of plant RNA degradome data revealed in this study may contribute to the alternative applications of degradome in RNA research.


Human NLRP3 inflammasome activation is Nox1-4 independent.
The NLRP3 inflammasome can be activated by pathogen-associated molecular patterns or endogenous danger-associated molecular patterns. The activation of the NLRP3 inflammasome results in proteolytic activation and secretion of cytokines of the interleukin-1 (IL-1) family. The precise mode of activation of the NLRP3 inflammasome is still elusive, but has been postulated to be mediated by reactive oxygen species (ROS) generated by an NADPH oxidase. Using primary cells from chronic granulomatous disease (CGD) patients lacking expression of p22(phox), a protein that is required for the function of Nox1-4, we show that cells lacking NADPH oxidase activity are capable of secreting normal amounts of IL-1beta. Thus, we provide evidence that activation of the NLRP3 inflammasome does not depend on ROS generated from an NADPH oxidase.


Women's and men's fertility preferences and contraceptive behaviors by HIV status in 10 sub-Saharan African countries.
This article draws on biomarker data from Demographic and Health Surveys (2003-2007) in 10 sub-Saharan African countries to examine differences in fertility preferences and contraceptive behaviors by HIV status for women and men, taking into account whether or not they probably know their HIV status. The objective is to determine if there are common patterns in the associations between these variables across several countries. Women's and men's fertility preferences and contraceptive behaviors are relatively similar across HIV status and probable knowledge of that status. However, two consistent differences emerge in some of the countries: HIV-positive women who probably know their status are less likely to want more children and are more likely to be using male condoms than women who are HIV-negative and probably know it. A similar association is observed for men for condom use but not for limiting childbearing. Other factors unrelated to HIV status seem to be shaping women's and men's unmet demand for contraception and use of methods other than the condom.


Autoimmune Neuromuscular Diseases Induced by Immunomodulating Drugs.
Immunomodulating drugs are widely used in autoimmune, transplant, and cancer patients. However, these drugs are associated with various autoimmune neuromuscular diseases such as demyelinating polyneuropathy, myasthenia gravis, and myositis. Early recognition of these complications and immediately terminating these drugs are very essential since some are life-threatening conditions. This review provides a general overview of drug-induced autoimmunity and autoimmune neuromuscular diseases associated with tumor necrosis factor alpha (TNF-α) antagonists, immune checkpoint inhibitors, and interferon (IFN) type 1 (IFN-β and IFN-α).


Impact of generic alendronate cost on the cost-effectiveness of osteoporosis screening and treatment.
Since alendronate became available in generic form in the Unites States in 2008, its price has been decreasing. The objective of this study was to investigate the impact of alendronate cost on the cost-effectiveness of osteoporosis screening and treatment in postmenopausal women. Microsimulation cost-effectiveness model of osteoporosis screening and treatment for U.S. women age 65 and older. We assumed screening initiation at age 65 with central dual-energy x-ray absorptiometry (DXA), and alendronate treatment for individuals with osteoporosis; with a comparator of "no screening" and treatment only after fracture occurrence. We evaluated annual alendronate costs of $20 through $800; outcome measures included fractures; nursing home admission; medication adverse events; death; costs; quality-adjusted life-years (QALYs); and incremental cost-effectiveness ratios (ICERs) in 2010 U.S. dollars per QALY gained. A lifetime time horizon was used, and direct costs were included. Base-case and sensitivity analyses were performed. Base-case analysis results showed that at annual alendronate costs of $200 or less, osteoporosis screening followed by treatment was cost-saving, resulting in lower total costs than no screening as well as more QALYs (10.6 additional quality-adjusted life-days). When assuming alendronate costs of $400 through $800, screening and treatment resulted in greater lifetime costs than no screening but was highly cost-effective, with ICERs ranging from $714 per QALY gained through $13,902 per QALY gained. Probabilistic sensitivity analyses revealed that the cost-effectiveness of osteoporosis screening followed by alendronate treatment was robust to joint input parameter estimate variation at a willingness-to-pay threshold of $50,000/QALY at all alendronate costs evaluated. Osteoporosis screening followed by alendronate treatment is effective and highly cost-effective for postmenopausal women across a range of alendronate costs, and may be cost-saving at annual alendronate costs of $200 or less.


Augmentation of Dispersion Entropy for Handling Missing and Outlier Samples in Physiological Signal Monitoring.
Entropy quantification algorithms are becoming a prominent tool for the physiological monitoring of individuals through the effective measurement of irregularity in biological signals. However, to ensure their effective adaptation in monitoring applications, the performance of these algorithms needs to be robust when analysing time-series containing missing and outlier samples, which are common occurrence in physiological monitoring setups such as wearable devices and intensive care units. This paper focuses on augmenting Dispersion Entropy (DisEn) by introducing novel variations of the algorithm for improved performance in such applications. The original algorithm and its variations are tested under different experimental setups that are replicated across heart rate interval, electroencephalogram, and respiratory impedance time-series. Our results indicate that the algorithmic variations of DisEn achieve considerable improvements in performance while our analysis signifies that, in consensus with previous research, outlier samples can have a major impact in the performance of entropy quantification algorithms. Consequently, the presented variations can aid the implementation of DisEn to physiological monitoring applications through the mitigation of the disruptive effect of missing and outlier samples.


Arthropod-borne virus antibodies in sera of residents of Kainji Lake Basin, Nigeria 1980.
A survey for haemagglutination-inhibiting arthropod-borne virus antibody was carried out in the Kainji Lake area of Nigeria. Of 267 persons tested, 139 (52%) and 158 (59%) had alphavirus and flavivirus group HI antibody, respectively. The prevalence of antibody to individual virus antigen is as follows: Chikungunya, 45%; Semliki Forest, 25%; Sindbis, 33%, Yellow fever, 31%, Dengue type 2, 46%; and Zika 56%. The presence of high antibody rates to Chikungunya, Dengue type 2 and Yellow fever viruses is of public health significance. These viruses have been identified as the most important arthropod-borne viruses causing human infections in Nigeria.


Immune transfer using spleen fragments.
The adequacy of spleen slices for the purpose of adoptive immune transfer was evaluated in rodents. Transfers using spleen cell suspensions and spleen slices were conducted in parallel from hyperimmune donors to non-immune intact and irradiated syngeneic recipients. It was demonstrated that the level of immune responsiveness attained with transfer of spleen slices was at least equal to and most often greater than that achieved with transfer of spleen cell suspensions.


Advanced imaging in acute ischemic stroke.
The evaluation and management of acute ischemic stroke has primarily relied on the use of conventional CT and MRI techniques as well as lumen imaging sequences such as CT angiography (CTA) and MR angiography (MRA). Several newer or less-established imaging modalities, including vessel wall MRI, transcranial Doppler ultrasonography, and 4D CTA and MRA, are being developed to complement conventional CT and MRI techniques. Vessel wall MRI provides high-resolution analysis of both extracranial and intracranial vasculature to help identify previously occult lesions or characteristics of lesions that may portend a worse natural history. Transcranial Doppler ultrasonography can be used in the acute setting as a minimally invasive way of identifying large vessel occlusions or monitoring the response to stroke treatment. It can also be used to assist in the workup for cryptogenic stroke or to diagnose a patent foramen ovale. Four-dimensional CTA and MRA provide a less invasive alternative to digital subtraction angiography to determine the extent of the clot burden and the degree of collateral blood flow in large vessel occlusions. Along with technological advances, these new imaging modalities are improving the diagnosis, workup, and management of acute ischemic stroke- roles that will continue to expand in the future.


The heart of the matter: health status of aged care clients receiving home- and community-based care.
Objective. To determine the current health status of home based elderly clients receiving government funded aged care packages. Design. Prospective Observational study. Setting. Community based, home care program in Australia. Participants. Community-dwelling older adults receiving aged care packages. Measurements. A comprehensive test battery of physical, mental and social scales were completed including a Caregiver Strain Index where appropriate. Results. 37% of the 334 subjects were male and the mean age was 81 ± 8 years. Physical functioning was low compared to the Australian population. Depression was highly prevalent with 15.9% severely depressed and 38.7% mildly depressed. 26% of clients screened positive for dementia. Relatively good levels of social support were reported, however social networking activity levels were low. Sixty one percent of clients had caregivers, of whom 63.3% had high levels of strain. Strain was higher in caregivers of clients on higher levels of care (78.5% versus 50.6% highly strained). Conclusion. The data suggests that as a group there is a high degree of comorbidity, and depression, dementia and caregiver strain are highly prevalent. The findings may aid administrators and health policy planners in directing resources to key areas impacting on health outcomes in this group.


Generation of a gene-corrected isogenic iPSC cell line from an X-linked retinoschisis patient with a hemizygous mutation c.304C > T (p.R102W) in RS1 gene.
X-linked retinoschisis (XLRS) is one of the most common retinal genetic diseases with progressive visual impairment in childhood affecting males. It is manifested with macular and/or peripheral schisis in neural retinas with no effective treatment. Previously, we successfully generated a human-induced pluripotent stem cell (iPSC) line from an XLRS patient carrying the hemizygous RS1 c. 304C > T (p.R102W) mutation. Here, we corrected the c.304C > T mutation in the RS1 gene using CRISPR/Cas9 technology to generate an isogenic control. This cell line is valuable for the study of XLRS.


Trends in the US and Canadian Pathologist Workforces From 2007 to 2017.
The current state of the US pathologist workforce is uncertain, with deficits forecast over the next 2 decades. To examine the trends in the US pathology workforce from 2007 to 2017. A cross-sectional study was conducted comparing the number of US and Canadian physicians from 2007 to 2017 with a focus on pathologists, radiologists, and anesthesiologists. For the United States, the number of physicians was examined at the state population level with a focus on pathologists. New cancer diagnoses per pathologist were compared between the United States and Canada. These data from the American Association of Medical Colleges Center for Workforce Studies' Physician Specialty Data Books and the Canadian Medical Association Masterfile were analyzed from January 4, 2019, through March 26, 2019. Numbers of pathologists were compared with overall physician numbers as well as numbers of radiologists and anesthesiologists in the United States and Canada. Between 2007 and 2017, the number of active pathologists in the United States decreased from 15 568 to 12 839 (-17.53%). In contrast, Canadian data showed an increase from 1467 to 1767 pathologists during the same period (+20.45%). When adjusted for each country's population, the number of pathologists per 100 000 population showed a decline from 5.16 to 3.94 in the United States and an increase from 4.46 to 4.81 in Canada. As a percentage of total US physicians, pathologists have decreased from 2.03% in 2007 to 1.43% in 2017. The distribution of US pathologists varied widely by state; per 100 000 population, Idaho had the fewest (1.37) and the District of Columbia had the most (15.71). When adjusted by new cancer cases per year, the diagnostic workload per US pathologist has risen by 41.73%; during the same period, the Canadian diagnostic workload increased by 7.06%. The US pathologist workforce decreased in both absolute and population-adjusted numbers from 2007 to 2017. The current trends suggest a shortage of US pathologists.


Risk of cancer in cases of suspected lynch syndrome without germline mutation.
Colorectal cancers (CRCs) with microsatellite instability (MSI) and a mismatch repair (MMR) immunohistochemical deficit without hypermethylation of the MLH1 promoter are likely to be caused by Lynch syndrome. Some patients with these cancers have not been found to have pathogenic germline mutations and are considered to have Lynch-like syndrome (LLS). The aim of this study was to determine the risk of cancer in families of patients with LLS. We studied a population-based cohort of 1705 consecutive patients, performing MSI tests and immunohistochemical analyses of MMR proteins. Patients were diagnosed with Lynch syndrome when they were found to have pathogenic germline mutations. Patients with MSI and loss of MSH2 and/or MSH6 expression, isolated loss of PMS2 or loss of MLH1 without MLH1 promoter hypermethylation, and no pathogenic mutation were considered to have LLS. The clinical characteristics of patients and the age- and sex-adjusted standardized incidence ratios (SIRs) of cancer in families were compared between groups. The incidence of CRC was significantly lower in families of patients with LLS than in families with confirmed cases of Lynch syndrome (SIR for Lynch syndrome, 6.04; 95% confidence interval [CI], 3.58-9.54; SIR for LLS, 2.12; 95% CI, 1.16-3.56; P < .001). However, the incidence of CRC was higher in families of patients with LLS than in families with sporadic CRC (SIR for sporadic CRC, 0.48; 95% CI, 0.27-0.79; P < .001). The risk of cancer in families with LLS is lower that of families with Lynch syndrome but higher than that of families with sporadic CRC. These results confirm the need for special screening and surveillance strategies for these patients and their relatives.


Hematological and Biochemical Parameters in Elite Soccer Players During A Competitive Half Season.
The purpose of the present study was to report and discuss the hematological and biochemical behavior of elite soccer players, in order to get more insight in the physiological characteristics of these sportsmen and to provide trainers and sports doctors with useful indicators. Nineteen male soccer players volunteered to participate in this study. We followed the young elite soccer players during a competitive half season. Venous blood samples were collected between 9:00 and 10:00 a.m. after an overnight fast (10 h) at baseline, after 45 and 90 days and hematological and biochemical parameters were measured. Hemoglobin and hematocrit levels were significantly reduced over the observational period (p<0.05), but erythrocyte count and iron levels remained unchanged. Bilirubin and ferritin levels significantly increased in response to regular soccer training (p<0.05). We observed a significant decrease in muscle enzyme plasma activity during the 90 days study period. ANOVA analysis revealed a significant increase in the leukocyte and neutrophil counts (p<0.05), in parallel with a significant decrease in the lymphocyte count (p<0.05) after the observational period of 90 days. Elite soccer players are characterized by significant changes in biochemical and hematological parameters over the half season, which are linked to training workload, as well as adaptation induced by the soccer training. Although the values of the measured parameters fell within the reference range, regular monitoring of the biochemical and hematological parameters is fundamental for the identification of a healthy status and related optimal performances by sport doctors and trainers and selection of a correct workload by trainers.


Histogenesis of the reticular groove of the buffalo (Bubalus bubalis) stomach.
Histogenesis of the reticular groove (sulcus reticuli) of the buffalo (Bubalus bubalis) was observed from primordial stage to birth. The epithelium of the reticular groove was considered early embryonic until a crown-rump (CR) length of 2.2 cm, and was uniformly distributed at CR 2.2 cm; superficial and basal zones developed by CR 3.2. cm. At CR 10.5 cm, the basal zone in the floor evaginated and formed longitudinal folds. At CR 25.5 cm, the basal zone in the lipids evaginated and formed papillae. The core of the longitudinal folds and papillae was formed by the lamina propria, muscularis mucosae, and submucosa. Keratinization was seen at CR 50.5 cm, and the epithelium was stratified squamous epithelium with keratinization, similar to that of the adult buffalo. The floor and lip had a single layer of muscle. A small oblique muscle layer was also found in the concavity of the lip. The correlation between structure and function of the reticular groove is discussed.


Longitudinal evaluation of the microleakage of dentin bonding agents used to seal resected root apices.
A material that bonds to dentin and seals both the root canal and exposed dentinal tubules would be desirable following root resection. The purpose of this study was to measure the sealing ability of four dentin bonding agents on the resected root end. The bonding systems evaluated were Amalgambond (AMB), Scotchbond Multi-Purpose (SMP), Prisma Universal Bond 3 (PUB 3), and All-Bond 2 (AB2). All materials were applied directly to the resected root end without a class I preparation. One-half of the roots in each group were contaminated with human blood before bonding. Microleakage was measured using fluid filtration at various time intervals from 1 to 24 wk. Results indicated that all dentin bonding agents significantly reduced apical microleakage compared with prebonded controls at all time intervals. Blood contamination did not adversely affect the sealing ability of AMB, PUB 3, or SMP. The blood-contaminated AB2 group displayed significantly greater microleakage after 12 and 24 wk than the uncontaminated roots.


Density of intimal smooth muscle cells in the coronary arteries of Bolivians.
To test an equation that uses measurements of fibroplastic intimal thickening and foam cell infiltrates, precursors for necrotic cores of atherosclerotic plaques in coronary arteries, to compute anticipated amounts of atheronecrosis. Data from New Orleans, La, and La Paz, Bolivia, afforded the opportunity to test the precision of the equation by comparing findings in separate populations. Coronary arteries retrieved at autopsy in La Paz, Bolivia, were processed into hematoxylin-eosin-stained paraffin sections along with a parallel series in New Orleans. The Bolivian data fit the equation without modification. Findings showed the precursors of atheronecrosis to progress at the slowest rate in Bolivians, at the fastest rate in New Orleans men, and at an intermediate rate in New Orleans women. The population with the most extensive atheronecrosis in aging subjects also had the greatest degrees of precursor changes in young adults. An equation that describes these principles precisely applies equally well to all three of the populations examined here, which are the only ones studied to date.


Methylation of simian virus 40 Hpa II site affects late, but not early, viral gene expression.
DNA methylation has been correlated with reduced gene expression in a number of studies, although evidence for a casual link between the two events has been lacking. Because microinjection of simian virus 40 (SV40) DNA into the nucleus of Xenopus laevis oocytes results in the synthesis of both early and late viral gene products, it was possible to test whether a specific methylation event can affect gene expression. The single SV40 Hpa II site at 0.72 SV40 map units was specifically methylated with Hpa II methylase. When this DNA was injected into oocytes, there was a marked reduction in the synthesis of the major late viral capsid protein VP-1, relative to the synthesis by an unmethylated control. However, production of the early proteins (the large and small tumor antigens) was not affected by Hpa II methylation. Therefore, methylation at a single site on the viral DNA located near the 5' end of the late region can specifically repress late gene expression. The possible mechanisms by which this repression is mediated are discussed.


CT-measured bone attenuation in patients with chronic obstructive pulmonary disease: relation to clinical features and outcomes.
Osteoporosis is highly prevalent in chronic obstructive pulmonary disease (COPD) patients and has been related to several clinical features. However, most studies have been in relatively small COPD cohorts. Therefore, the objectives of this study were to compare bone attenuation measured on low-dose chest computed tomography (CT) between COPD subjects and smoker and nonsmoker controls, and to relate bone attenuation to clinical parameters, inflammatory biomarkers, and outcomes in a large, well-characterized COPD cohort. We studied 1634 COPD subjects, 259 smoker controls, and 186 nonsmoker controls who participated in a large longitudinal study (ECLIPSE). We measured bone attenuation, extent of emphysema, and coronary artery calcification (Agatston score) on baseline CT scans, and clinical parameters, inflammatory biomarkers, and outcomes. Bone attenuation was lower in COPD subjects compared with smoker and nonsmoker controls (164.9 ± 49.5 Hounsfield units [HU] versus 183.8 ± 46.1 HU versus 212.1 ± 54.4 HU, p < 0.001). Bone attenuation was not significantly different between COPD subjects and smoker controls after adjustment for age, sex, and pack-years of smoking. In the COPD subjects, bone attenuation correlated positively with forced expiratory volume in 1 second (FEV₁, r = 0.062, p = 0.014), FEV₁/forced vital capacity (FVC) ratio (r = 0.102, p < 0.001), body mass index (r = 0.243, p < 0.001), fat-free mass index (FFMI, r = 0.265, p < 0.001), and C-reactive protein (r = 0.104, p < 0.001), and correlated negatively with extent of emphysema (r = -0.090, p < 0.001), Agatston score (r = -0.177, p < 0.001), and interleukin-8 (r = -0.054, p = 0.035). In a multiple regression model, older age, lower FFMI and higher Agatston score were associated with lower bone attenuation. Lower bone attenuation was associated with higher exacerbation (r = -0.057, p = 0.022) and hospitalization (r = -0.078, p = 0.002) rates but was not associated with all-cause mortality. In conclusion, CT-measured bone attenuation was lower in COPD subjects compared with nonsmoker controls but not compared with smoker controls, after adjustment for age, sex, and pack-years of smoking. In the COPD subjects, bone attenuation was associated with age, body composition, and coronary artery calcification but was not associated with all-cause mortality.


The influence of frequency, intensity, volume and mode of strength training on whole muscle cross-sectional area in humans.
Strength training is an important component in sports training and rehabilitation. Quantification of the dose-response relationships between training variables and the outcome is fundamental for the proper prescription of resistance training. The purpose of this comprehensive review was to identify dose-response relationships for the development of muscle hypertrophy by calculating the magnitudes and rates of increases in muscle cross-sectional area induced by varying levels of frequency, intensity and volume, as well as by different modes of strength training. Computer searches in the databases MEDLINE, SportDiscus and CINAHL were performed as well as hand searches of relevant journals, books and reference lists. The analysis was limited to the quadriceps femoris and the elbow flexors, since these were the only muscle groups that allowed for evaluations of dose-response trends. The modes of strength training were classified as dynamic external resistance (including free weights and weight machines), accommodating resistance (e.g. isokinetic and semi-isokinetic devices) and isometric resistance. The subcategories related to the types of muscle actions used. The results demonstrate that given sufficient frequency, intensity and volume of work, all three types of muscle actions can induce significant hypertrophy at an impressive rate and that, at present, there is insufficient evidence for the superiority of any mode and/or type of muscle action over other modes and types of training. Tentative dose-response relationships for each variable are outlined, based on the available evidence, and interactions between variables are discussed. In addition, recommendations for training and suggestions for further research are given.


Frequent expression of glypican-3 in Merkel cell carcinoma: an immunohistochemical study of 55 cases.
The pathologic diagnosis of Merkel cell carcinoma (MCC) is mainly based on routine morphology and a characteristic cytokeratin 20 (CK20) immunohistochemical staining pattern. However, about 10% to 15% of MCCs are reportedly CK20 negative and about 10% to 20% of MCCs have only focal CK20 positivity. We aimed to study glypican-3 (GPC3) expression in MCC and to compare it with CK20 expression in MCC. Immunohistochemical expression of GPC-3, CK20, and CD23 were studied in 55 cases of MCC and 21 cases of noncutaneous small cell neuroendocrine carcinoma (SCNC), including 10 cases of pulmonary SCNC and 11 cases of nonpulmonary SCNC. The results of GPC3 expression in these tumors were then compared with that of CK20. Of the 55 cases, 39 were positive for GPC3 (70.9%). Seventy-seven percent of the positive MCCs (30/39) showed GPC3 immunoreactivity in > or = 30% tumor cells. Of the 55 cases, 53 were positive for CK20 (96%); 49 of them showed CK20 immunoreactivity in > or = 30% tumor cells. All MCC cases were either positive for both GPC3 and CK20 (37 cases) or at least 1 of the markers (18 cases, 16 CK20 only and 2 GPC3 only). In addition, we studied GPC3 and CK20 expression in 10 cases of pulmonary SCNC and 11 cases of nonpulmonary SCNC. Three of ten pulmonary SCNC and 5 of 11 nonpulmonary SCNC expressed GPC3. All pulmonary SCNC and 9 of 11 nonpulmonary SCNC were negative for CK20. All cases of MCC and SCNC were negative for CD23. In conclusion, GPC3 is frequently expressed in SCNC of various origins, in particular in MCC, which, in combination with CK20, may represent another useful marker in the diagnosis of MCC.


Epidemiology of infectious encephalitis causes in 2016.
We performed a literature search in the Medline database, using the PubMed website. The incidence of presumably infectious encephalitis is estimated at 1.5-7 cases/100,000 inhabitants/year, excluding epidemics. Infectious encephalitis and immune-mediated encephalitis share similar clinical signs and symptoms. The latter accounts for a significant proportion of presumably infectious encephalitis cases without any established etiological diagnosis; as shown from a prospective cohort study where 21% of cases were due to an immune cause. Several infectious agents are frequently reported in all studies: Herpes simplex virus (HSV) is the most frequent pathogen in 65% of studies, followed by Varicella-zoster virus (VZV) in several studies. Enteroviruses are also reported; being the most frequent viruses in two studies, and the 2nd or 3rd viruses in five other studies. There are important regional differences, especially in case of vector-borne transmission: Asia and the Japanese encephalitis virus, Eastern and Northern Europe/Eastern Russia and the tick-borne encephalitis virus, Northern America and Flavivirus or Alphavirus. Bacteria can also be incriminated: Mycobacterium tuberculosis and Listeria monocytogenes are the most frequent, after HSV and VZV, in a French prospective study. The epidemiology of encephalitis is constantly evolving. Epidemiological data may indicate the emergence and/or dissemination of new causative agents. The dissemination and emergence of causative agents are fostered by environmental, social, and economical changes, but prevention programs (vaccination, vector controls) help reduce the incidence of other infectious diseases and associated encephalitis (e.g., measles).


Hematopoietic cell transformation by a murine recombinant retrovirus containing the src gene of Rous sarcoma virus.
A recombinant murine retrovirus (MRSV) containing the src gene of avian Rous sarcoma virus (RSV) was shown to induce hematopoietic colonies in infected mouse bone marrow. MRSV-induced colony formation followed single-hit kinetics and required mercaptoethanol in the agar medium. Cells from the colonies induced by MRSV could be established as continuous cell lines that demonstrated unrestricted self-renewal in vitro and tumorigenicity in vivo. The transformants, all of which expressed high levels of the Rous sarcoma virus transforming protein, pp60src, appeared to be at an early stage in lymphoid cell differentiation. They lacked Fc receptors and detectable immunoglobulin mu heavy chain synthesis, markers normally associated with committed B cells. The majority of the MRSV-transformed cell lines contained high levels of terminal deoxynucleotidyl transferase, an enzyme present in lymphoid progenitor cells committed to the T-cell lineage. One cell line expressed Thy-1 antigen, but none expressed Lyt-1 and Lyt-2, markers of more differentiated T cells. These findings demonstrate that the src gene is capable of transforming cells of hematopoietic origin.


Spatial distribution of tuberculosis and relationship with living conditions in an urban area of Campina Grande--2004 to 2007.
This research aimed to study the spatial distribution of tuberculosis and its relationship with living conditions in the urban area of the city of Campina Grande in the period from 2004 until 2007. It is an ecologic study which used the city's neighborhood distribution; demographic, social and economic data from year 2000 census; and the new cases of tuberculosis reported to the Disease and Reporting Information System. Georeferencing was done for the cases of tuberculosis, and disease incidence was calculated by neighborhood. Rates were softened and the Global Moran Index was calculated. Social-economic data were grouped in quartiles according to the Life Condition Index, calculating the incidence of TB in each stratum of living conditions. The results showed that the spatial distribution of tuberculosis in the city is not uniform. Grouping neighborhoods according to the Life Conditions Index revealed social differences that can justify the occurrence of higher incidence rates in the most socially and economically vulnerable regions. The best living condition stratum presented a high incidence possibly due to the underreporting of the cases of tuberculosis caused mainly by the centralization of disease control services. We hope that this study may help outline control strategies for the city of Campina Grande, from the perspective of health promotion, for a disease so socially determined, as is the case of TB.


Development of a new class of potent and highly selective G protein-coupled receptor kinase 5 inhibitors and structural insight from crystal structures of inhibitor complexes.
G protein-coupled receptor kinase 5 (GRK5) is an important drug development target for heart failure, cardiac hypertrophy, and cancer. We have designed and developed a new class of highly selective, potent, and non-covalent GRK5 inhibitors. One of the inhibitors displayed GRK5 IC50 value of 10 nM and exhibited >100,000-fold selectivity over GRK2. The X-ray structure of a ketoamide-derived inhibitor-bound GRK5 showed the formation of a hemithioketal intermediate with active site Cys474 in the GRK5 active site and provided new insights into the ligand-binding site interactions responsible for high selectivity. The current studies serve as an important guide to therapeutic GRK5 inhibitor drug development.


Liver transplantation for patients with alcoholism and end-stage liver disease.
Liver transplantation for alcoholic cirrhosis remains controversial. In particular, criteria for the selection of patients who will remain recovered from alcoholism post-transplant require better definition. We analyzed the long-term predictive value of categorizing transplant referral patients with alcoholism and end-stage liver disease into risk groups for recidivism and noncompliance. Forty-seven patients with the diagnosis of alcoholism and advanced liver disease were evaluated and placed into predefined risk groups (low-, moderate-, and high-risk) for recidivism and noncompliance. No absolute period of abstinence from alcohol was required. All patients were asked to sign a contract not to drink alcohol and comply with a rehabilitation program before and after transplantation. Compliance with alcohol rehabilitation, abstinence, functional level, employment, and survival were assessed. Patients who were not compliant with the rehabilitation program or consumed alcohol were scored as failures. Thirty-one patients were ranked as low risk, and were accepted for liver transplantation; 27 patients were transplanted. Five of 31 patients (16%) drank alcohol. One patient drank before and four patients drank transiently after transplantation. Ten patients were categorized as moderate risk, and were deferred for transplantation; two patients underwent later transplantation. All 10 patients (100%) were noncompliant or drank alcohol, including two patients who drank after transplantation after a period of abstinence and rehabilitation. Six patients were ranked as high risk, and were denied liver transplantation. Five patients (83%) drank alcohol and were noncompliant. Minimum follow-up was 12 months (mean, 24 months; range, 12-41 months). The mean Karnofsky performance score was 34 before and 84 after liver transplantation. Actuarial survival of alcoholic patients undergoing transplantation was 93%. We conclude that categorization of transplant referral patients with alcoholism and liver failure into predefined risk groups for recidivism and noncompliance accurately predicts pre- and post-transplant behavior. As defined, only low-risk alcoholic patients are good candidates for liver transplantation.


Patients' perceptions and views of surgery and radioiodine ablation in the definitive management of Graves' disease.
Patients' perceptions and preferences influence the choice of radioiodine ablation (RIA) or surgery in the definitive management of Graves' disease. This study aimed to evaluate their concerns, experiences and satisfaction following definitive treatment. A postal survey of patients who had treatment with surgery or RIA between January 2011 and June 2013 for Graves' disease was conducted. Of 214 patients, 136 (64%) responded. The majority of patients felt actively involved in decision making (83.8%) and were satisfied (84.9%) with their treatment. Compared with RIA, patients who underwent surgery were more satisfied with their treatment (p=0.008). Discussion with the doctor was the most useful aid to decision making. Feeling involved in decision-making process was associated with improved satisfaction (p<0.001).Common reasons for not choosing surgery were need for general anaesthesia, scarring and voice change. Avoiding close contact, risk of persistent hyperthyroidism and worsening eye disease were common reasons for not choosing RIA. Ongoing concerns were hypothyroidism, scarring and eye problems after surgery and hypothyroidism and eye problems after RIA. This study provides insight into patients' experiences of surgery and RIA for Graves' disease and reinforces the importance of patient involvement in the decision-making process.


Drift-resistant SNR scalable video coding.
We address the problem of enhancement layer drift estimation for fine granular scalable video. An optimal per-pixel drift estimation algorithm is introduced. The encoder assumes that there is some truncation of the enhancement layer, which does not allow the enhancement layer reference to be properly reconstructed, and the encoder recursively estimates the associated drift and chooses coding modes accordingly. The approach yields performance gains of about 1 dB across low to medium rates. In addition, we investigate dual frame prediction, for both base and enhancement layer, with pulsed-quality allocation in the base


[Echo-Doppler study of myxomatous mitral valve insufficiency and the results of reparative surgery].
The aim of conservative management of mitral regurgitation caused by floppy mitral valve is to restore a valvular function which closely resembles that of normal physiology. Fifty-eight patients affected by floppy mitral valve underwent surgical procedures for severe mitral regurgitation due to chordal elongation and/or rupture. Of these, 28 presented posterior mitral prolapse corrected by quadrangular excision of the prolapsed part and posterior anuloplasty achieved by apposition of a polytetrafluoroethylene conduit. The remaining 30 patients presented anterior or bilateral prolapse corrected by transposition of chordae from the posterior leaflet to the anterior cusp together together with anuloplasty. A complete echo-Doppler study was performed preoperatively, 10 days after the operation and every 6 months thereafter. Mean follow-up was 16.1 +/- 6.3 months. Preoperatively, 44 patients presented severe mitral regurgitation and 14 had moderate regurgitation (quantified by means of pulsed Doppler). All patients showed severe enlargement of the left cavities (LVDD 67.1 +/- 8.6 mm, left atrium 53.4 +/- 10.9 mm) with normal mitral area (6.08 +/- 2.14 sqcm, Doppler measurement). Following surgery we found a significant reduction in: 1) the degree of mitral regurgitation (29 patients had no regurgitation; 20 had mild protosystolic mitral regurgitation (29 patients had no regurgitation; 20 had mild protosystolic mitral regurgition, confirmed by color-M-mode; moderate or severe regurgitation was found in 6 cases); 2) the left ventricle and left atrium dimensions (LVDD 53.4 +/- 5.2 mm, p less than 0.01; left atrium 43.8 +/- 11.1 mm, p less than 0.01). Color flow imaging provided information about the recovery of a normal valvular function.(ABSTRACT TRUNCATED AT 250 WORDS)


Negative fateful life events in midlife and advanced predicted brain aging.
Negative fateful life events (FLEs) such as interpersonal conflict, death in the family, financial hardship, and serious medical emergencies can act as allostatic stressors that accelerate biological aging. However, the relationship between FLEs and neuroanatomical aging is not well understood. We examined 359 men (mean age 62 years) participating in the Vietnam Era twin study of aging (VETSA) to determine whether negative midlife FLEs are associated with advanced brain aging after controlling for physical, psychological, and lifestyle factors. At two different time points, participants were assessed for negative FLEs, health and well-being, general cognitive ability, socioeconomic status, depression, and ethnicity. Participants underwent a magnetic resonance imaging examination, and T1-weighted images were processed with FreeSurfer. Subsequent neuroanatomical measurements were entered into the Brain-Age Regression Analysis and Computation Utility software (BARACUS) to predict brain age. Having more midlife FLEs, particularly relating to interpersonal relationships, was associated with advanced predicted brain aging (i.e., higher predicted brain age relative to chronological age). This association remained after controlling for the significant covariates of alcohol consumption, cardiovascular risk, adult socioeconomic status, and ethnicity.


Altered metabolic enzyme activities in fast and slow twitch muscles due to induced sciatic neuropathy in the rat.
A pilot study was conducted to examine enzymatic and metabolic alterations in end organs as a consequence of neuropathy. Silastic pellets were implanted transverse to the sciatic nerve of rats. Neurobehavioral evaluations based on hind limb gait were conducted at 2 and 4 weeks postoperatively. Four-week values demonstrated facilitated utilization of the neuropathic limb in three of five animals, as compared to the normal contralateral limb and normal animals. Nerve electrophysiology and quantitative muscle enzymology were observed at 4 weeks postoperatively. Relative to control animals, the experimental group exhibited decreased nerve conduction velocity, decreased glycolytic enzyme activity in both fast and slow twitch muscle and increased malate dehydrogenase activity in the flexor digitorum longus (FDL). Muscle weight/body weight ratios for control and experimental animals suggest an increase for experimental animals, especially of the FDL. This change was not due to increased muscle proteins for the experimental group as determined on homogenates. Muscle homogenate protein values were actually significantly lower than those of the control group for FDL and soleus. For this reason, when enzyme activities were compared on an equal protein basis, most significant differences were obscured. Only aldolase remained significantly less for the experimental group (p less than 0.01). It is concluded that muscle metabolism is subject to change when confronted with mildly neuropathic innervation. Of particular interest is the uniform direction of change. Both fast and slow twitch muscles exhibited a metabolic shift in the direction of slow twitch muscle.


DNA transfer by examination tools--a risk for forensic casework?
The introduction of profiling systems with increased sensitivity has led to a concurrent increase in the risk of detecting contaminating DNA in forensic casework. To evaluate the contamination risk of tools used during exhibit examination we have assessed the occurrence and level of DNA transferred between mock casework exhibits, comprised of cotton or glass substrates, and high-risk vectors (scissors, forceps, and gloves). The subsequent impact of such transfer in the profiling of a target sample was also investigated. Dried blood or touch DNA, deposited on the primary substrate, was transferred via the vector to the secondary substrate, which was either DNA-free or contained a target sample (dried blood or touch DNA). Pairwise combinations of both heavy and light contact were applied by each vector in order to simulate various levels of contamination. The transfer of dried blood to DNA-free cotton was observed for all vectors and transfer scenarios, with transfer substantially lower when glass was the substrate. Overall touch DNA transferred less efficiently, with significantly lower transfer rates than blood when transferred to DNA-free cotton; the greatest transfer of touch DNA occurred between cotton and glass substrates. In the presence of a target sample, the detectability of transferred DNA decreased due to the presence of background DNA. Transfer had no impact on the detectability of the target profile, however, in casework scenarios where the suspect profiles are not known, profile interpretation becomes complicated by the addition of contaminating alleles and the probative value of the evidence may be affected. The results of this study reiterate the need for examiners to adhere to stringent laboratory cleaning protocols, particularly in the interest of contamination minimisation, and to reduce the handling of items to prevent intra-item transfer.