Mechanisms of recovery from aphasia: evidence from positron emission tomography studies.
Language functions comprise a distributed neural system, largely lateralised to the left cerebral hemisphere. Late recovery from aphasia after a focal lesion, other than by behavioural strategies, has been attributed to one of two changes at a systems level: a laterality shift, with mirror region cortex in the contralateral cortex assuming the function(s) of the damaged region; or a partial lesion effect, with recovery of perilesional tissue to support impaired language functions. Functional neuroimaging with PET allows direct observations of brain functions at systems level. This study used PET to compare regional brain activations in response to a word retrieval task in normal subjects and in aphasic patients who had shown at least some recovery and were able to attempt the task. Emphasis has been placed on single subject analysis of the results as there is no reason to assume that the mechanisms of recovery are necessarily uniform among aphasic patients. Six right handed aphasic patients, each with a left cerebral hemispheric lesion (five strokes and one glioma), were studied. Criteria for inclusion were symptomatic or formal test evidence of at least some recovery and an ability to attempt word retrieval in response to heard word cues. Each patient underwent 12 PET scans using oxygen-15 labelled water (H2(15)O) as tracer to index regional cerebral blood flow (rCBF). The task, repeated six times, required the patient to think of verbs appropriate to different lists of heard noun cues. The six scans obtained during word retrieval were contrasted with six made while the subject was "at rest". The patients' individual results were compared with those of nine right handed normal volunteers undergoing the same activation study. The data were analysed using statistical parametric mapping (SPM96, Wellcome Department of Cognitive Neurology, London, UK). Perception of the noun cues would be expected to result in bilateral dorsolateral temporal cortical activations, but as the rate of presentation was only four per minute the auditory perceptual activations were not evident in all people. Anterior cingulate, medial premotor (supplementary speech area) and dorsolateral frontal activations were evident in all normal subjects and patients. There were limited right dorsolateral frontal activations in three of the six patients, but a similar pattern was also found in four of the nine normal subjects. In the left inferolateral temporal cortex, activation was found for the normal subjects and five of the six patients, including two of the three subjects with lesions involving the left temporal lobe. The only patient who showed subthreshold activation in the left inferolateral temporal activation had a very high error rate when performing the verb retrieval task. The normal subjects showed a left lateralised inferolateral temporal activation, reflecting retrieval of words appropriate in meaning to the cue from the semantic system. Lateralisation of frontal activations to the left was only relative, with right prefrontal involvement in half of the normal subjects. Frontal activations are associated with parallel psychological processes involved in word retrieval, including task initiation, short term (working) memory for the cue and responses, and prearticulatory processes (even though no overt articulation was required). There was little evidence of a laterality shift of word retrieval functions to the right temporal lobe after a left hemispheric lesion. In particular, left inferolateral temporal activation was seen in all patients except one, and he proved to be very inefficient at the task. The results provide indirect evidence that even limited salvage of peri-infarct tissue with acute stroke treatments will have an important impact on the rehabilitation of cognitive functions.


Re-evaluation of methaemoglobin reduction as a screening procedure for glucose-6-phosphate dehydrogenase (G6PD).
Methaemoglobin reduction method is considered to be an old method of qualitative analysis of glucose-6-phosphate dehydrogenase with low specificity and sensitivity and as such, many are sceptical about the reliability of the outcome of the result of the methodology.The aims of this study were to determine the sensitivity and specificity of methaemoglobin reduction method and examine its suitability as a routine method for the screening of glucose-6-phosphate dehydrogenase in this environment. One hundred children were recruited into the study which was conducted over a period of one year. The children (males and females) were aged between 1 day and 15 years. G6PD screening by methaemoglobin reduction method was carried out on all the subjects, while G6PD qualitative assay using G6PD assay kits by Biolabo (France), was carried out in the first 15 subjects who were G6PD deficient by the qualitative screening and the first 15 subjects who were G6PD normal. This was to compare the qualitative with the quantitative assay results and thereby determine the sensitivity and specificity of the methaemoglobin reduction method. The sensitivity and specificity of methaemoglobin reduction test was found to be 93.3 percent each. The results of the qualitative methaemoglobin reduction test for the G6PD deficiency compared well with the quantitative enzymatic assay. With sensitivity and specificity each of 93.3%, the simple qualitative test is dependable and therefore suitable for screening for G6PD.


FRET Studies of Quinolone-Based Bitopic Ligands and Their Structural Analogues at the Muscarinic M1 Receptor.
Aiming to design partial agonists as well as allosteric modulators for the M1 muscarinic acetylcholine (M1AChR) receptor, two different series of bipharmacophoric ligands and their structural analogues were designed and synthesized. The hybrids were composed of the benzyl quinolone carboxylic acid (BQCA)-derived subtype selective allosteric modulator 3 and the orthosteric building block 4-((4,5-dihydroisoxazol-3-yl)oxy)-N,N-dimethylbut-2-yn-1-amine (base of iperoxo) 1 or the endogenous ligand 2-(dimethylamino)ethyl acetate (base of acetylcholine) 2, respectively. The two pharmacophores were linked via alkylene chains of different lengths (C4, C6, C8, and C10). Furthermore, the corresponding structural analogues of 1 and 2 and of modified BQCA 3 with varying alkyl chain length between C2 and C10 were investigated. Fluorescence resonance energy transfer (FRET) measurements in a living single cell system were investigated in order to understand how these compounds interact with a G protein-coupled receptor (GPCR) on a molecular level and how the single moieties contribute to ligand receptor interaction. The characterization of the modified orthosteric ligands indicated that a linker attached to an orthoster rapidly attenuates the receptor response. Linker length elongation increases the receptor response of bitopic ligands, until reaching a maximum, followed by a gradual decrease. The optimal linker length was found to be six methylene groups at the M1AChR. A new conformational change is described that is not of inverse agonistic origin for long linker bitopic ligands and was further investigated by exceptional fragment-based screening approaches.


[Interrelationship between lipoxygenase metabolites of arachidonic acid and pulmonary blood flow and ventilation in acute pneumonia].
High-pressure liquid chromatography was used to measure the blood content of lipoxygenase metabolites (LM) of arachidonic acid: leukotriene B4 (LTB4) and hydroxyeicosatetraene acids (5 HETE, 12 HETE, 15 HETE) in 65 patients with acute pneumonia (AP) of mild gravity (group 1) and of medium gravity (group 2), in 23 patients with acute bronchitis (AB), and in 15 normal male persons aged 18 to 20 years. In all the examined, the zonal pulmonary blood flow was measured by regional rheopulmonography. External respiratory function (ERF) was also determined together with the recording of the flow-volume loop. At the height of AP and AB, all the patients demonstrated an increase of LM in the blood, with the maximum LM content being recorded in group 2. During convalescence, AB and AP patients of group 1 manifested normalization of the majority of the parameters. In group 2, they significantly exceeded the control level. 5 and 15 HETE had the closest correlations with the blood flow parameters, whereas LTB4 and 12 HETE had less intensive correlations. The influences of LM such as 5 and 15 HETE on the pulmonary blood flow were associated with deterioration of the blood content of the lungs and venous return, the action of LTB4 was coupled with venous congestion formation, that of 12 HETE with the rise of vascular resistance. Close negative correlations of LTB4 and 5 HETE with the majority of ERF parameters indicate that they are important factors in the pathogenesis of restrictive and obstructive ventilatory disorders.(ABSTRACT TRUNCATED AT 250 WORDS)


A zero-shot learning approach to the development of brain-computer interfaces for image retrieval.
Brain decoding-the process of inferring a person's momentary cognitive state from their brain activity-has enormous potential in the field of human-computer interaction. In this study we propose a zero-shot EEG-to-image brain decoding approach which makes use of state-of-the-art EEG preprocessing and feature selection methods, and which maps EEG activity to biologically inspired computer vision and linguistic models. We apply this approach to solve the problem of identifying viewed images from recorded brain activity in a reliable and scalable way. We demonstrate competitive decoding accuracies across two EEG datasets, using a zero-shot learning framework more applicable to real-world image retrieval than traditional classification techniques.


Prognostic Factors for Development of Subsequent Metastases in Localized Osteosarcoma: A Systematic Review and Identification of Literature Gaps.
To investigate prognostic factors in pediatric and young adult patients with localized osteosarcoma that could predict the development of subsequent pulmonary metastases and lead to an ability to risk-stratify therapy. We performed a systematic review of the literature published since January 1990 to establish common evidence-based prognostic factors. PubMed and Embase searches (Jan 1990-Aug 2018) were performed. Two reviewers independently selected papers for patients with localized osteosarcoma with subsequent metastatic development and then reviewed for quality of methods and prognostic factors. Database searches yielded 216 unique results. After screening, 27 full-text articles were studied in depth, with 9 items fulfilling predetermined inclusion and exclusion criteria. Age, tumor location, tumor size/volume, and histologic response carried independent prognostic value in the majority of the studies. Several prognostic factors seemed to be consistent amongst the studies, but the heterogeneity and smaller sizes of the study populations made pooling of results difficult. Standardization of larger patient populations and consistent definitions/cutoffs for prognostic factors are needed to further assess for consistent prognostic factors and potential predictive models to be developed.


[Effect of acute aprotinin (Gordox) therapy on hemostasis in heart surgery patients, with special reference to hyperfibrinolysis].
Authors have studied the effect of Gordox-therapy on haemostasis after open heart surgery in a prospective clinical trial. Thirty seven patients (pts) undergoing cardiac surgery due to their valve disease were randomly assigned either to control-group (20 pts) or to Gordox-group (17 pts). The patients in the Gordox group were given Gordox according the following scheme: 2 M IU within 20 min. after induction of anaesthesia followed by 0.5 M IU/hour infusion until the end of the operation. One M IU also was given into the oxygenator before starting the extracorporeal circulation. The postoperative chest tube drainage was less in Gordox-group (534 +/- 260 ml vs. 987 +/- 583 ml, p less than 0.005), and donor blood and fresh frozen plasma requirement was also lower in this group (534 +/- 633 ml vs. 935 +/- 718 ml p less than 0.05; 70 +/- 153 ml vs. 211 +/- 245 ml p less than 0.05, respectively). There was no significant difference between the two groups concerning the postoperative activated partial thromboplastin time, prothrombin time, thrombin time values. The authors could document significantly higher fibrinogen concentration and significantly lower fibrinolytic activity postoperatively in the Gordox-group (p less than 0.05). Gordox therapy has advantageous effect on haemostasis after open heart surgery which can be documented both by clinical and laboratory examination.


Evaluation and integration of disparate classification systems for clefts of the lip.
Orofacial clefting is a common birth defect with wide phenotypic variability. Many systems have been developed to classify cleft patterns to facilitate diagnosis, management, surgical treatment, and research. In this review, we examine the rationale for different existing classification schemes and determine their inter-relationships, as well as strengths and deficiencies for subclassification of clefts of the lip. The various systems differ in how they describe and define attributes of cleft lip (CL) phenotypes. Application and analysis of the CL classifications reveal discrepancies that may result in errors when comparing studies that use different systems. These inconsistencies in terminology, variable levels of subclassification, and ambiguity in some descriptions may confound analyses and impede further research aimed at understanding the genetics and etiology of clefts, development of effective treatment options for patients, as well as cross-institutional comparisons of outcome measures. Identification and reconciliation of discrepancies among existing systems is the first step toward creating a common standard to allow for a more explicit interpretation that will ultimately lead to a better understanding of the causes and manifestations of phenotypic variations in clefting.


A High-Yielding Rice Cultivar "Takanari" Shows No N Constraints on CO2 Fertilization.
Enhancing crop yield response to elevated CO2 concentrations (E-[CO2]) is an important adaptation measure to climate change. A high-yielding indica rice cultivar "Takanari" has recently been identified as a potential candidate for high productivity in E-[CO2] resulting from its large sink and source capacities. To fully utilize these traits, nitrogen should play a major role, but it is unknown how N levels influence the yield response of Takanari to E-[CO2]. We therefore compared grain yield and quality of Takanari with those of Koshihikari, a standard japonica cultivar, in response to Free-Air CO2 enrichment (FACE, +200 μmol mol-1) under three N levels (0, 8, and 12 g m-2) over three seasons. The biomass of both cultivars increased under E-[CO2] at all N levels; however, the harvest index decreased under E-[CO2] in the N-limited treatment for Koshihikari but not for Takanari. The decreased harvest index of Koshihikari resulted from limited enhancement of spikelet number under N-limitation. In contrast, spikelet number increased in E-[CO2] in Takanari even without N application, resulting in significant yield enhancement, averaging 18% over 3 years, whereas Koshihikari exhibited virtually no increase in yield in E-[CO2] under the N-limited condition. Grain appearance quality of Koshihikari was severely reduced by E-[CO2], most notably in N-limited and hot conditions, by a substantial increase in chalky grain, but chalky grain % did not increase in E-[CO2] even without N fertilizer. These results indicated that Takanari could retain its high yield advantage over Koshihikari with limited increase in chalkiness even under limited N conditions and that it could be a useful genetic resource for improving N use efficiency under E-[CO2].


Cell envelope and cell wall immunization of Macaca fascicularis: effect on the progression of ligature-induced periodontitis.
The nonhuman primate, Macaca fascicularis, was used to study the role of immunization with selected members of the periodontopathic microbiota in the longitudinal progression of ligature-induced periodontitis. Animals were immunized with cell envelope antigens prepared from Porphyromonas gingivalis and Prevotella intermedia, and a mixture prepared from Fusobacterium nucleatum, Campylobacter rectus, and Actinomyces viscosus. Serum immunoglobulin G (IgG), IgM and IgA isotype antibodies increased significantly in all immunization groups and were specific for each of the immunogens. P. gingivalis and P. intermedia immunization resulted in a stabilization of the proportions of these species throughout most of the experiment. The high P. gingivalis antibody titer resulted in low P. gingivalis numbers being recovered. P. gingivalis immunization, while lowering recoverable viable P. gingivalis, resulted in significantly increased levels of Prevotella loescheii, Prevotella buccae, Bacteroides macacae and Prevotella melaninogenica compared with preligation and preimmunization levels. Actinobacillus actinomycetemcomitans, Capnocytophaga spp. and Eikenella spp. remained at preligation levels postimmunization. Campylobacter spp. increased significantly during the course of the experiment in all groups, whereas the levels of Fusobacterium spp. decreased. Plaque indices and bleeding on probing showed significant increases in all groups following ligation, with the placebo group showing the greatest increase. Pocket depth measurements revealed that , whereas the placebo animals showed an approximate 5% increase, the P. gingivalis- and P. intermedia-immunized groups showed nearly a 20% increase in pocket depth. Attachment level measurements showed significantly greater attachment loss in the P. gingivalis- and P. intermedia-immunized groups, and the F. nucleatum + C. rectus + A. viscosus immunization appeared to prevent significant changes in pocket depth/attachment level loss. Radiographic measurement of bone loss by computer-assisted densitometric image analysis revealed that the placebo group lost bone throughout the experiment. P. gingivalis- and P. intermedia-immunized groups showed an exacerbated loss of bone density and the group immunized with F. nucleatum + C. rectus + A. viscosus exhibited significantly lower amounts of bone loss when analyzed by computer-assisted densitometric image analysis, compared with the other immunized groups. Although immunization with P. gingivalis and P. intermedia cell envelope antigens had an effect on their emergence in the complex microbiota of the developing periodontal pocket, this immunization also resulted in greater bone loss than immunization with F. nucleatum + C. rectus + A. viscosus, suggesting that, whereas selective members of the putative periodontopathic microbiota may play a direct role in periodontal tissue destruction, the complexity of the subgingival microbiota dictates that considerable scrutiny is required to select useful immunogens that can elicit functional protection from periodontal tissue destruction induced by oral microorganisms that already colonize or infect the host.


Adverse stress, hippocampal networks, and Alzheimer's disease.
Recent clinical data have implicated chronic adverse stress as a potential risk factor in the development of Alzheimer's disease (AD) and data also suggest that normal, physiological stress responses may be impaired in AD. It is possible that pathology associated with AD causes aberrant responses to chronic stress, due to potential alterations in the hypothalamic-pituitary-adrenal (HPA) axis. Recent study in rodent models of AD suggests that chronic adverse stress exacerbates the cognitive deficits and hippocampal pathology that are present in the AD brain. This review summarizes recent findings obtained in experimental AD models regarding the influence of chronic adverse stress on the underlying cellular and molecular disease processes including the potential role of glucocorticoids. Emerging findings suggest that both AD and chronic adverse stress affect hippocampal neural networks in a similar fashion. We describe alterations in hippocampal plasticity, which occur in both chronic stress and AD including dendritic remodeling, neurogenesis, and long-term potentiation. Finally, we outline potential roles for oxidative stress and neurotrophic factor signaling as the key determinants of the impact of chronic stress on the plasticity of neural networks and AD pathogenesis.


Hemophilia C: A Case Report With Updates on Diagnosis and Management of a Rare Bleeding Disorder.
Hemophilia C or factor XI deficiency is a rare clotting disorder with prevalence of only 1 per 1 million. A 24-year-old male with multiple abdominal surgeries complicated by wound infections and poor healing was admitted to plastic surgery service for an elective abdominoplasty. Hematology was consulted for increased intraoperative and postoperative bleeding. Laboratory workup showed high-normal activated plasma thromboplastin time of 31 s (reference: 23 - 34 s), prothrombin time (PT) of 15 s (reference: 11.8 - 14.3 s) and internationalized normal ratio (INR) of 1.2. Patient had normal factors VIII, IX, XIII levels and normal von Willebrand's factor level. The factor XI level came back at 0.28 (0.44 - 1.43 U/mL) diagnostic for intermediate factor XI deficiency. Factor XI is responsible for thrombin generation after clotting is initiated as well as clot stabilization. The confirmatory test is factor XI assay. The management of factor-XI deficiency is based on history of bleeding and nature of the procedure.


Location of a highly conserved neutralizing epitope in the F glycoprotein of human respiratory syncytial virus.
Trypsin digestion of the purified F protein from human respiratory syncytial virus (Long strain) generated a set of fragments in the amino-terminal third of the F1 subunit which contained the epitope 47F involved in neutralization. Sequencing of five escape mutant viruses selected with monoclonal antibody 47F allowed us to map precisely two amino acid residues (262 and 268) of the F1 subunit which are essential for the integrity of this important epitope. The results are discussed in terms of the mechanisms involved in virus neutralization and the design of potential synthetic vaccines.


Construction of meanings during life-limiting illnesses and its impacts on palliative care: Ethnographic study in an African context.
Knowledge about how people make meaning in cancer, palliative, and end-of-life care is particularly lacking in Africa, yet it can provide insights into strategies for improving palliative care (PC). This study explored ways in which cancer patients, their families, and health care professionals (HCPs) construct meaning of their life-limiting illnesses and how this impact on provision and use of PC in a Nigerian hospital. This ethnographic study utilised participant observation, informal conversations during observation, and interviews to gather data from 39 participants, comprising service users and HCPs in a Nigerian hospital. Data were analysed using Spradley's framework for ethnographic data analysis. Meaning-making in life-limiting illness was predominantly rooted in belief systems. Most patients and their families, including some HCPs, perceived that cancer was caused by the devil, mystical, or supernatural beings. They professed that these agents manifested in the form of either spiritual attacks or that wicked people in society used either poison or acted as witches/wizards to inflict cancer on someone. These beliefs contributed to either nonacceptance of, or late presentation for, PC by most of patients and their families, while some professionals depended on supernatural powers for divine intervention and tacitly supporting religious practices to achieve healing/cure. Findings revealed that cultural and religious world views about life-limiting illnesses were used in decision-making process for PC. This, therefore, provided evidence that could improve the clinicians' cultural competence when providing PC to individuals of African descent, especially Nigerians, both in Nigerian societies and in foreign countries.


A lophotrochozoan-specific nuclear hormone receptor is required for reproductive system development in the planarian.
Germ cells of sexually reproducing organisms receive an array of cues from somatic tissues that instruct developmental processes. Although the nature of these signals differs amongst organisms, the importance of germline-soma interactions is a common theme. Recently, peptide hormones from the nervous system have been shown to regulate germ cell development in the planarian Schmidtea mediterranea; thus, we sought to investigate a second class of hormones with a conserved role in reproduction, the lipophilic hormones. In order to study these signals, we identified a set of putative lipophilic hormone receptors, known as nuclear hormone receptors, and analyzed their functions in reproductive development. We found one gene, nhr-1, belonging to a small class of functionally uncharacterized lophotrochozoan-specific receptors, to be essential for the development of differentiated germ cells. Upon nhr-1 knockdown, germ cells in the testes and ovaries fail to mature, and remain as undifferentiated germline stem cells. Further analysis revealed that nhr-1 mRNA is expressed in the accessory reproductive organs and is required for their development, suggesting that this transcription factor functions cell non-autonomously in regulating germ cell development. Our studies identify a role for nuclear hormone receptors in planarian reproductive maturation and reinforce the significance of germline-soma interactions in sexual reproduction across metazoans.


Iron-responsive bacterial small RNAs: variations on a theme.
For most living organisms, iron is both essential and potentially toxic, making the precise maintenance of iron homeostasis necessary for survival. To manage this paradox, bacteria regulate the acquisition, utilization, and storage of iron in response to its availability. The iron-dependent ferric uptake repressor (Fur) often mediates this iron-responsive regulation by both direct and indirect mechanisms. In 2002, Masse and Gottesman identified a novel target of Fur-mediated regulation in Escherichia coli: a gene encoding a small regulatory RNA (sRNA) termed RyhB. Under conditions of iron-limitation, RyhB is produced and functions to regulate the expression of several target genes encoding iron-utilizing enzymes, iron acquisition systems, and iron storage factors. This pivotal finding provided the missing link between environmental iron-limitation and previously observed decreases in certain iron-dependent metabolic pathways, a phenomenon now referred to as an "iron-sparing" response. The discovery of RyhB opened the door to the rapidly expanding field of bacterial iron-regulated sRNAs, which continue to be identified and described in numerous bacterial species. Most striking are findings that the impact of iron-responsive sRNA regulation often extends beyond iron homeostasis, particularly with regard to production of virulence-associated factors by pathogenic bacteria. This review discusses trends in the collective body of work on iron-regulated sRNAs, highlighting both the regulatory mechanisms they utilize to control target gene expression and the impact of this regulation on basic processes controlling bacterial physiology and virulence.


[Significance of the TDP-43 deposition in FTLD-U and ALS].
Tau-negative and ubiquitin-positive inclusions (UPI) are the pathological hallmarks of frontotemporal lobar degeneration (FTLD-U) and amyotrophic lateral sclerosis (ALS). Recently, TDP-43, a heterogeneous nuclear ribonucleoprotein was identified as a component of these UPI. However, it remains to be determined whether TDP-43 is the major component of UPI, because only antibodies recognizing both normal and abnormal TDP-43 have been available. We raised antibodies to phosphopeptides representing 36 out of 64 candidate phosphorylation sites of human TDP-43. Of the generated antibodies, pS379, pS403/404, pS409, pS410 and pS409/410 clearly labeled UPI and glial cytoplasmic inclusions but not the nuclei. Immunoblot analyses of sarkosyl insoluble fractions demonstrated that the phosphorylation-specific antibodies recognized TDP-43 at -45 kDa, smearing substances and the -25 kDa fragment, all of which were present in the brains of FTLD-U and ALS but not controls. These antibodies did not recognize normal TDP-43 at 43 kDa. These results clearly indicate that abnormally phosphorylated full-length TDP-43 and the C-terminal fragments are the major component of UPI in FTLD-U and ALS. These findings together with recent discovery of mutations in the TDP-43 gene in ALS strongly suggest that TDP-43 is the


Heated debates on regulations of heated tobacco products in South Korea: the news valence, source and framing of relative risk/benefit.
We analyse news representations of the regulation of heated tobacco products (HTPs) in South Korea, the country where HTP use is among the highest in the world despite conflicts between the government and the HTP manufacturers. We analysed a total of 571 print and TV news covering HTP regulations, published between 2017 and 2018, the time period when HTPs were introduced to the country and various regulations of HTPs were proposed and implemented. We assessed the prevalence and associations among specific types of HTP regulations that were discussed, valence towards regulation, sources, framing of the relative health risks/benefits of HTPs compared with conventional cigarettes. Taxation (55.2%) and warning labels (25.7%) were two regulation topics covered the most. Almost equal proportions of pro-regulation (2.5%) and anti-regulation valence (2.2%) were found in taxation-related news, while pro-regulation valence appeared more frequently for other restrictions, including warning labels (pro=9.5% vs anti=1.4%), marketing restrictions (pro=6.9% vs anti=0%) and integration of HTPs into smoke-free policies for cigarettes (pro=8.7% vs anti=0%). The government (59%), followed by the tobacco industry (39.4%), was the source cited most often across news stories while the presence of tobacco control advocates was low (4.9%). As for framing, there was no significant difference in the prevalence of stories mentioning reduced harm (31.7%) and equal or more harm (33.6%) of HTPs compared with cigarettes. We provide implications for governments and tobacco control advocates on building consensus for applying cigarette equivalent taxes and pictorial warning labels to HTPs.


Sigmoid and gastric tonometry during infrarenal aortic aneurysm repair.
The value of the sigmoid tonometer in predicting sigmoid ischaemia and postoperative enteric organism infection has been reported but the value of tonometric measurement has been challenged. The purpose of this study was to examine the use of tonometric measurements in a series of patients undergoing infrarenal aortic aneurysm repair. We assessed the results obtained when sigmoid (n=11) and gastric (n=8) tonometry were performed in patients undergoing infrarenal aortic aneurysm repair (n=11). We measured blood flow ultrasonically (n=6) in the inferior mesenteric artery(IMA) and IMA stump pressures. Sigmoid and gastric tonometry were measured prior to clamping of the infrarenal aorta, during cross clamping and after clamp release at 1, 4, 16 and 20h. Ultrasonic flow was measured before clamping. Stump pressures in the IMA were measured before, during and after clamping. The IMA was chronically occluded in five patients. The IMA flow was 37.5 +/- 8.7 mL/min (mean +/- s.e.). The mean IMA stump pressures before, during and after clamping were 64 +/- 13, 48 +/- 8 and 69 +/- 10 mmHg, respectively, and did not differ significantly. Mean systematic arterial pressures at these times were 89 +/- 7, 95 +/- 5 and 86 +/- 8 mmHg. These did not differ significantly or when compared with IMA stump pressure. The gradient between systemic arterial pressure and IMA stump pressure did not vary significantly at any of these times. Sigmoid and gastric intramucosal pH (pHi) did not differ significantly at any of the above times. Both sigmoid gastric pHi dropped on clamp application but 4 h afterwards had returned to baseline levels. Systemic arterial pH reflected significant ischaemia during clamping and shortly after release of the clamp(P=0.008). Tonometry may reflect systemic events as much as regional ischaemia. Useful tonometry results may depend on the development of a trend rather that individual measurements. The routine use of tonometry to detect intestinal ischaemia may not be cost-effective in aortic surgery.


Evaluation of surveillance of contacts of new tuberculosis cases in the state of Mato Grosso - Brazil.
To evaluate surveillance of contacts of new tuberculosis cases in the state of Mato Grosso from 1999 to 2004. This was a descriptive epidemiological study based on data from the Tuberculosis Case Registry Database. The number of new tuberculosis cases, the number of contacts (estimated, investigated, and uninvestigated), and the tuberculosis incidence rate were analyzed by age bracket. The mean rate of contacts investigated for each case of tuberculosis by age bracket was calculated per year of study. The cases of pulmonary tuberculosis with and without contacts investigated were analyzed by sputum smear microscopy results. In 2004, there were 41.3 cases of tuberculosis per 100,000 inhabitants in the state of Mato Grosso. The south-central region presented the highest incidence rate (57 cases/100,000 inhabitants) and a 15% rate of contacts investigated. Among those younger than 15 years, 63 contacts (60.5%) were investigated, whereas among those aged 15 or older, 389 (8.9%) were investigated. In 1999, the mean rate of contacts investigated statewide was 0.02 (0.5%), and, in 2004, it reached 0.42 (10.5%). The percentage of contacts investigated was 40% higher among the contacts of contagious cases (OR = 1.4; 95% CI: 1.08-1.83). The percentage of contacts investigated is very low, principally among adults. The adoption of the standards for investigation of tuberculosis contacts proposed by the Brazilian National Ministry of Health Department of Health Surveillance has not ensured that this group at highest risk of developing active tuberculosis be given priority at health care facilities in the state of Mato Grosso.


Hormone-induced enlargement of receptive fields in trigeminal mechanoreceptive neurons. I. Time course, hormone, sex and modality specificity.
The phenomenon of hormone induced enlargement of receptive field area in mechanoreceptive neurons was investigated with respect to time course, hormone, sex and modality specificity. In acute recording experiments, threshold receptive field boundaries of single trigeminal ganglion neurons innervating the facial region of rats were determined for several different treatment groups. Among ovariectomized females injected with estradiol benzoate (EB) for 2, 5 or 10 days, receptive field areas were significantly increased after only 2 days. Enlargement of field areas appeared to be maximal after 5 days of EB. Lordosis behavior was observed after 10 days of EB but not after 2 or 5 days, suggesting that receptive field enlargement occurs independently of hormone induced lordosis behavior. In normal, intact females, receptive field area varied significantly with the estrous cycle (large during estrus, small during diestrus) indicating that this phenomenon is naturally occurring, not dependent upon the method of estrogen administration. Progesterone given for 10 days had no effect on receptive field area. Treatment with 2 days of EB followed by a single progesterone injection produced reliable lordosis but did not result in any further increase in receptive field area beyond the increase produced by 2 days of EB alone. Thus the synergism between estrogen and progesterone that is recognized for induction of lordosis is absent with respect to receptive field enlargement. The small increase in field area following 10 days of testosterone treatment could be accounted for by the fact that such animals, had blood serum estradiol levels comparable to animals given 2 or 5 days of EB, possibly the result of a testosterone to estrogen conversion. It was concluded that hormone induced receptive field enlargement appears specific for estrogen. Castrated male rats treated with 10 days of EB show the same increase in receptive field area as females, indicating that the phenomenon is not specific to females. Analysis of receptive field area as a function of receptive field type and adaptation rate showed that EB induced field area enlargement was specific to rapidly adapting mechanoreceptive neurons.


[Microecology of the gastrointestinal tract of chronic enteritis patients].
The results obtained in the simultaneous study of the microbiology of different sections of the gastrointestinal tract (the oral cavity, the stomach, the large and small intestines) in chronic enteritis patients, as well as in the study of biopsy mucosa samples from the small intestine of such patients, are presented. This method has been shown to give a complete picture indicating both the severity of dysbiotic disturbances in the patient and the degree of their spread in the alimentary canal, which should be taken into account in clinical practice for the determination of the severity of the disease, the rational course of treatment and the time of the discharge of the patient from the hospital.


Portable bedside microcomputer system for management of parenteral nutrition in all age groups.
A microcomputer program has been designed to provide comprehensive assistance to the clinician in prescribing parenteral nutrition in children of all ages. It is implemented on a fully portable, independent machine that can be taken to the bedside anywhere in the hospital. The user is guided through a standardised prescribing process based on a well tried protocol and taking into account the patient's age, clinical condition, concurrent parenteral infusions, laboratory findings, and enteral intake. A printout is produced for insertion into the patient's clinical record, giving all concerned in the care of the child a clear, legible record of when, how, and by whom the prescription was calculated. The user can review and amend the proposed prescription before printing, giving ultimate control to the prescriber, not the computer. The system saves time by performing accurately the necessary calculations, and provides financial savings by reducing wastage of parenteral nutrition during the re-introduction of enteral feeding.


Characterization of beta-1 and beta-2 adrenoceptors in guinea pig atrium: functional and receptor binding studies.
The selective beta-2 adrenoceptor agonist procaterol produced positive inotropic and chronotropic responses over a concentration range of 1 nM to 0.1 mM in spontaneously beating right atria and in three of seven electrically driven left atria. The pD2 values (right atria, 7.30; left atria, 7.18) were midway between its known affinities at beta-1 and beta-2 adrenoceptors and are evidence that positive inotropic and chronotropic responses involve a minor beta-2 adrenoceptor component. The pKB values for procaterol against (-)-isoproterenol in the right atria (5.59) and left atria (5.29) were consistent with its affinity for beta-1 adrenoceptors and suggest that these are responsible primarily for positive inotropic and chronotropic responses. Receptor binding studies in right atrial homogenates showed that [125I]cyanopindolol binding was saturable (KD = 36.2 pM, maximal density of binding sites = 49.2 fmol mg-1 protein) and stereoselective with respect to the isomers of propranolol. Competition binding curves for the beta-1 adrenoceptor antagonist CGP 20712A and beta-2 selective antagonist ICI 118,551 against [125I]cyanopindolol binding were resolved into two components using iterative curve fitting techniques. Binding sites with the characteristics of beta-1 and beta-2 adrenoceptors were present in the proportions of approximately 75 to 25%. These studies indicate either that the beta-1 adrenoceptor is coupled more efficiently to the positive inotropic and chronotropic response than the beta-2 adrenoceptor or that a proportion of the beta-2 adrenoceptors subserve other functions.


A Dual-Circular RNA Signature as a Non-invasive Diagnostic Biomarker for Gastric Cancer.
Gastric cancer (GC) is the TOP3 leading cause of human mortality in malignant tumors. Notwithstanding, the association between GC and circRNAs is not clear. The purpose of this research was to determine the association between GC progression and circRNAs. The data of circRNAs was obtained from the Gene Expression Omnibus (GEO) database to identify gene, which differentially expressed circRNAs in GC tissues and paired normal tissues. The expression of circRNAs in cancer tissues and normal tissues were tested, and the target circRNA was verified before and after surgery in the plasma. A circRNA-micro(mi)RNA-mRNA competing endogenous RNAs (ceRNAs) network was established, and GO and KEGG analysis are performed. Five candidate circRNAs were identified through bioinformatics analysis. Hsa_circ_0021087 and hsa_circ_0005051 were both downregulated in GC tissues, cells and plasma by RTq-PCR. Additionally, there was a significant difference in the expression of plasma hsa_circ_0021087 in patients with GC at the preoperative and postoperative stages (P < 0.001). Hsa_circ_0021087 also promoted the proliferation of GC cells in vitro. Next, the circRNA-miRNA-mRNA network of hsa_circ_0021087 was predicted, which may be associated with the development of GC by bioinformatics analysis. In summary, the aforementioned dual-circular RNAs may have important implications on the potential, novel and non-invasive diagnostic method for patients with GC.


Feasibility of Using Source-Level Brain Computer Interface for People with Multiple Sclerosis.
This work evaluates the feasibility of using a source level Brain-Computer Interface (BCI) for people with Multiple Sclerosis (MS). Data used was previously collected EEG of eight participants (one participant with MS and seven neurotypical participants) who performed imagined movement of the right and left hand. Equivalent current dipole cluster fitting was used to assess related brain activity at the source level and assessed using dipole location and power spectrum analysis. Dipole clusters were resolved within the motor cortices with some notable spatial difference between the MS and control participants. Neural sources that generate motor imagery originated from similar motor areas in the participant with MS compared to the neurotypical participants. Power spectral analysis indicated a reduced level of alpha power in the participant with MS during imagery tasks compared to neurotypical participants. Power in the beta band may be used to distinguish between left and right imagined movement for users with MS in BCI applications.Clinical Relevance- This paper demonstrates the cortical areas activated during imagined BCI-type tasks in a participant with Multiple Sclerosis (MS), and is a proof of concept for translating BCI research to potential users with MS.


Long-term follow-up of attenuated plaques in patients with acute myocardial infarction: an intravascular ultrasound substudy of the HORIZONS-AMI trial.
Intravascular ultrasound (IVUS)-attenuated plaque is characterized by absence of ultrasound signal behind hypoehcoic plaque and is seen almost exclusively in acute coronary syndromes. We analyzed poststenting and 13-month follow-up IVUS in 186 patients (195 lesions) with acute myocardial infarction who underwent primary percutaneous coronary intervention. The primary prespecified IVUS end point was the in-stent percent net volume obstruction at follow-up. Overall, 70.3% of lesions contained attenuated plaques at baseline. During follow-up, attenuation scores decreased significantly, behind paclitaxel-eluting stents (PES) (14.1 [11.9, 16.3] to 7.7 [5.4, 9.9], P<0.0001), behind bare metal stents (BMS) (18.5 [13.2, 23.8] to 12.0 [6.7, 17.3], P<0.0001), and within distal references (3.1 [1.1, 5.1] to 2.2 [0.2, 4.1], P=0.02). There was a greater calcium increase in attenuated than nonattenuated plaques in both PES (Δcalcium score of 4.4 [3.3, 5.5] versus 1.6 [0.9, 2.3], P<0.0001) and BMS (Δcalcium score of 4.1[2.3, 5.9] versus 1.0 [0.3, 1.7], P=0.001). PES implantation into attenuated plaques was particularly associated with late acquired stent malapposition (36.8% versus 15.4% compared with nonattenuated plaques treated with PES, P=0.03). Changes in attenuation scores correlated with changes in calcium scores both in PES (Pearson correlation coefficient=-0.456, P<0.0001] and BMS sites (Pearson correlation coefficient=-0.450, P=0.0006). In 3 years of follow-up, target lesion revascularization was significantly less in patients with attenuated plaque at baseline (6.0% versus 17.4% in patient without attenuated plaques, P=0.019). Attenuated plaques evolved into calcified plaques after stent implantation. Attenuated plaque is associated with late acquired stent malapposition and related less target lesion revascularization (consistent with less neointimal hyperplasia), especially after PES implantation in patients with acute myocardial infarction. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00433966.


Influence of English language in the number of citations of articles published in Brazilian journals of ophthalmology.
To determine the association between language and number of citations of ophthalmology articles published in Brazilian journals. This study was a systematic review. Original articles were identified by review of documents published at the two Brazilian ophthalmology journals indexed at Science Citation Index Expanded - SCIE ["Arquivos Brasileiros de Oftalmologia (ABO)" and "Revista Brasileira de Oftalmologia (RBO)"]. All document types ("articles" and "reviews") listed at SCIE in English (English Group) or in Portuguese (Portuguese Group) from January 1, 2008 to December 31, 2009 were included, except: "editorial materials"; "corrections"; "letters"; and "biographical items". The primary outcome was the number of citations through the end of second year after publication date. Subgroup analysis included likelihood of citation (cited at least once versus no citation), journal, and year of publication. The search at the web of science revealed 382 articles [107 (28%) in the English Group and 275 (72%) in the Portuguese Group]. Of those, 297 (77.7%) were published at the ABO and 85 (23.3%) at the RBO. The citation counts were statistically significantly higher (P<0.001) in the English Group (1.51 - SD 1.98 - range 0 to 11) compared with the Portuguese Group (0.57 - SD 1.06 - range 0 to 7). The likelihood citation was statistically significant higher (P<0.001) in the English Group (70/107 - 65.4%) compared with the Portuguese Group (89/275 - 32.7%). There were more articles published in English at the ABO (98/297 - 32.9%) than at the RBO (9/85 - 10.6%) [P<0.001]. There were no significant difference (P=0.967) at the proportion of articles published in English at the years 2008 (48/172 - 27.9%) and 2009 (59/210 - 28.1%). The number of citations of articles published in Portuguese at Brazilian ophthalmology journals is lower than the published in English. The results of this study suggest that the editorial boards should strongly encourage the authors to adopt English as the main language in their future articles.


[How much does a caesarean section cost in Madagascar? Socio-economical aspects and caesarean sections rate in Toamasina, Madagascar 1999-2001].
The maternal mortality is a major issue of public health in developing countries. Essential obstetric cares, especially caesarean section, play a crucial role in the decrease of maternal mortality. WHO, FNUAP and UNICEF estimate that the minimum acceptable rate of caesarean section in developing countries must reach 5% to guarantee safety for both the new-born and the mother. In Madagascar; the average national rate of caesarean section was 0.6% in 1997. In the area of Toamasina, this rate was 0.7%. To increase the number of women who can access to those essential obstetric cares, several solutions may be followed. One of them is to develop health insurance for pregnant women. This kind of solution seems to be well accepted and equitable. To reach this goal, this study was carried out to define sociodemographic characteristics of women who got caesarean section in Toamasina, to assess the cost of a caesarean section at the CHR (regional hospital) of Toamasina, and to measure the evolution of the caesarean section rate in the area. A retrospective survey was carried out for the years 1999, 2000 and 2001 including all women who got a caesarean section in the area of Toamasina: in the hospital of Toamasina and in the one of Fenerive-Est. Data were collected in both hospitals. 748 women were included in the survey The cost-analysis consisted in a partial medico-economic cost analysis which was measured from the patient's point of view. Sociodemographic characteristics are comparable with the results found in the literature. The mean age of the women involved was 28+/-7 years. The main indications for caesarean section were foeto-pelvic disproportion (37%) and placenta praevia (12%). The maternal mortality rate was 3%. The rate of infantile mortality was 18%. The cover rate of caesarean section in the area of the CHR is estimated respectively at 0.58%, 0.67% and 0.71% for the years 1999, 2000 and 2001. Data collection step was very difficult to carry out. The rates of death among the mother (0.3%) and among the new-born (18%) were definitely too important. But, these rates were comparable with those found in the bibliography. The cover rate of the caesarean section is too low, however it was increasing during these 3 years. About 2000 women per year needed a caesarean without having it. The cost for the society of the morbidity and the mortality caused by the lack of availability of caesarean section is drastic. The price of a caesarean section is about 250 000 Fmg (approximately 36 euros). The average income is about 170 000 Fmg (25 euros) per month per inhabitant. Thus, the price asked was dramatically too high for a majority of people. The availability of caesarean section had to be improved in the area of Toamasina. More than ten years after the first International Conference about the Maternity without Risk in Nairobi, it appeared that something had to be done quickly in Madagascar. The solution to develop a public health insurance, or others actions, seemed to be relevant and urgent.


Amygdala Atrophy and Its Functional Disconnection with the Cortico-Striatal-Pallidal-Thalamic Circuit in Major Depressive Disorder in Females.
Major depressive disorder (MDD) is approximately twice as common in females than males. Furthermore, female patients with MDD tend to manifest comorbid anxiety. Few studies have explored the potential anatomical and functional brain changes associated with MDD in females. Therefore, the purpose of the present study was to investigate the anatomical and functional changes underlying MDD in females, especially within the context of comorbid anxiety. In this study, we recruited antidepressant-free females with MDD (N = 35) and healthy female controls (HC; N = 23). The severity of depression and anxiety were evaluated by the Hamilton Depression Rating Scale (HAM-D) and the Hamilton Anxiety Rating Scale (HAM-A), respectively. Structural and resting-state functional images were acquired on a Siemens 3.0 Tesla scanner. We compared the structural volumetric differences between patients and HC with voxel-based morphometry (VBM) analyses. Seed-based voxel-wise correlative analyses were used to identify abnormal functional connectivity. Regions with structural deficits showed a significant correlation between gray matter (GM) volume and clinical variables that were selected as seeds. Furthermore, voxel-wise functional connectivity analyses were applied to identify the abnormal connectivity relevant to seed in the MDD group. Decreased GM volume in patients was observed in the insula, putamen, amygdala, lingual gyrus, and cerebellum. The right amygdala was selected as a seed to perform connectivity analyses, since its GM volume exhibited a significant correlation with the clinical anxiety scores. We detected regions with disrupted connectivity relevant to seed primarily within the cortico-striatal-pallidal-thalamic circuit. Amygdaloid atrophy, as well as decreased functional connectivity between the amygdala and the cortico-striatal-pallidal-thalamic circuit, appears to play a role in female MDD, especially in relation to comorbid anxiety.


Interaction of NuMA protein with the kinesin Eg5: its possible role in bipolar spindle assembly and chromosome alignment.
Bipolar spindle assembly in mitotic cells is a prerequisite to ensure correct alignment of chromosomes for their segregation to each daughter cell; spindle microtubules are tethered at plus ends to chromosomes and focused at minus ends to either of the two spindle poles. NuMA (nuclear mitotic apparatus protein) is present solely in the nucleus in interphase cells, but relocalizes during mitosis to the spindle poles to play a crucial role in spindle assembly via focusing spindle microtubules to each pole. In the present study we show that the kinesin-5 family motor Eg5 is a protein that directly interacts with NuMA, using a proteomics approach and various binding assays both in vivo and in vitro. During mitosis Eg5 appears to interact with NuMA in the vicinity of the spindle poles, whereas the interaction does not occur in interphase cells, where Eg5 is distributed throughout the cytoplasm but NuMA exclusively localizes to the nucleus. Slight, but significant, depletion of Eg5 in HeLa cells by RNA interference results in formation of less-focused spindle poles with misaligned chromosomes in metaphase; these phenotypes are similar to those induced by depletion of NuMA. Since NuMA is less accumulated at the spindle poles in Eg5-depleted cells, Eg5 probably contributes to spindle assembly via regulating NuMA localization. Furthermore, depletion of cytoplasmic dynein induces mislocalization of NuMA and phenotypes similar to those observed in NuMA-depleted cells, without affecting Eg5 localization to the spindles. Thus dynein appears to control NuMA function in conjunction with Eg5.


Hormone replacement therapy in children with hypogonadotropic hypogonadism: where do we stand?
To characterize hormone replacement therapy in a cohort of adolescent males and females with hypogonadotropic hypogonadism (HH) with a focus on changes in management during the past 10 years. Medical records of patients followed for HH during the past 10 years were reviewed. A total of 45 patients (22 female: 23 male) with HH were identified. The average age at HH diagnosis was 14.48 ± 2.02 years in females and 14.89 ± 1.64 years in males (P = .53). In females, the average age of pubertal induction was 14.53 ± 1.86 years. Conjugated equine estrogen was used in 54.5%, transdermal estradiol in 41%, and oral estradiol in 4.5%. The average duration to cycling was 1.96 ± 0.78 years. A progressive increase in the use of transdermal estradiol was noted over time, with 100% of females being started on this regimen since 2008. In males, the average age of induction was 15.22 ± 1.41 years. All were started on intramuscular testosterone cypionate at various doses. The average duration to full adult replacement was 1.95 ± 0.51 years. There is no current standard of care to guide pubertal induction in adolescents with HH. However, a significant increase in the use of transdermal estrogen was noted in females during the past 10 years. While much less variability in pubertal induction was seen in males, wide disparities in doses and escalation schedules were found. Prospective studies aimed at elucidating optimal strategies for sex steroid replacement in this pediatric population are badly needed.


Breaking bad news in amyotrophic lateral sclerosis: the need for medical education.
The manner in which physicians deliver difficult diagnoses is an area of discontent for patients with amyotrophic lateral sclerosis (ALS). The American Academy of Neurology's Practice Parameter for care of the ALS Patient recommended teaching and evaluating strategies for disclosing the diagnosis (10). Our objective was to examine residents' ability in and perceptions of communicating the diagnosis of ALS. Twenty-two resident physicians were videotaped and rated by two ALS neurologists as they delivered an ALS diagnosis to a standardized patient (SP) during an objective structured clinical examination (OSCE). Residents self-rated immediately after the OSCE, again after viewing their videotape, and completed a survey regarding the OSCE and delivering difficult diagnoses. OSCE performance was suboptimal, particularly for communication skills and empathy. The two examiners' scores correlated except for the empathy subscore. Residents' self-assessments did not align with the examiners' scores either before or after watching their videotape. The survey uncovered residents' apprehension and dissatisfaction with their training in diagnosis delivery. The results highlight a need for resident education in delivering an ALS diagnosis. The lack of correlation between residents' and examiners' scoring requires further study. Evaluation of empathy is particularly challenging. Residents agreed that OSCE participation was worthwhile.


Efficacy of entecavir-tenofovir combination therapy for chronic hepatitis B patients with multidrug-resistant strains.
The emergence of multidrug-resistant (MDR) strains of hepatitis B virus (HBV) is a major concern. This study aimed to investigate the efficacy and safety of combination therapy with entecavir (ETV) plus tenofovir disoproxil fumarate (TDF) against MDR HBV. To adjust for differences in baseline characteristics, inverse probability weighting (IPW) using propensity scores for the entire cohort and weighted Cox proportional hazards models were applied. Ninety-three consecutive patients who were treated with ETV-TDF combination therapy for >6 months were included; at baseline, 45 were infected with HBV strains with genotypic resistance to lamivudine (LAM) and ETV (the LAM/ETV-R group), 28 with strains resistant to LAM and adefovir (ADV) (the LAM/ADV-R group), and 20 with strains resistant to LAM, ETV, and ADV (the LAM/ETV/ADV-R group). The median duration of rescue therapy was 13.0 (range, 6.7 to 31.7) months. Seventy-four of 93 patients (79.6%) achieved complete virologic suppression, after a median of 4.5 (95% confidence interval, 3.0 to 6.0) months. The cumulative probability of complete virologic suppression at month 6 was 63.6% (55.7%, 75.0%, and 65.0% in the LAM/ETV-R, LAM/ADV-R, and LAM/ETV/ADV-R groups, respectively). During the treatment period, these probabilities were not significantly different across the resistance profiles before and after IPW (P = 0.072 and P = 0.510, respectively). In multivariate analysis, a lower baseline HBV DNA level, but not resistance profiles, was an independent predictor of complete virologic suppression. Renal dysfunction was not observed during the treatment period. In conclusion, rescue therapy with ETV-TDF combination is efficient and safe in patients infected with MDR HBV strains regardless of the antiviral drug resistance profiles.


High-Frequency Heart Rate Variability Reactivity and Trait Worry Interact to Predict the Development of Sleep Disturbances in Response to a Naturalistic Stressor.
High-frequency heart rate variability (HF-HRV) reactivity was proposed as a vulnerability factor for stress-induced sleep disturbances. Its effect may be amplified among individuals with high trait worry or sleep reactivity. This study evaluated whether HF-HRV reactivity to a worry induction, sleep reactivity, and trait worry predict increases in sleep disturbances in response to academic stress, a naturalistic stressor. A longitudinal study following 102 undergraduate students during an academic semester with well-defined periods of lower and higher academic stress was conducted. HF-HRV reactivity to a worry induction, trait worry using the Penn State Worry Questionnaire, and sleep reactivity using the Ford Insomnia Stress Reactivity Test were measured during the low stress period. Sleep disturbances using the Pittsburgh Sleep Quality Index were assessed twice during the lower stress period and three times during the higher stress period. Greater reductions in HF-HRV in response to the worry induction predicted increases in sleep disturbances from the lower to the higher academic stress period. Trait worry moderated this association: individuals with both higher trait worry and greater HF-HRV reactivity to worry had larger increases in stress-related sleep disturbances over time, compared to participants with lower trait worry and HF-HRV reactivity. A similar, but marginally significant effect was found for sleep reactivity. This study supports the role of HF-HRV reactivity as a vulnerability factor for stress-induced sleep disturbances. The combination of high trait worry and high HF-HRV reactivity to worry might identify a subgroup of individuals most vulnerable to stress-related sleep disturbances.


Psychometric Properties of the Merrill-Palmer-Revised Scales of Development in Preschool Children With Autism Spectrum Disorder.
Psychometrically sound tests of intellectual ability are indispensable for research and assessment of children with autism spectrum disorder (ASD), yet few tests have been validated for use with this population. The Merrill-Palmer-Revised Scales of Development (M-P-R) is a standardized test of intellectual ability that was validated for use with typically developing preschoolers. The current study's aim was to investigate the criterion validity of the M-P-R for assessing cognitive skills in preschoolers with ASD (N = 180). Good concurrent validity was demonstrated, with a large positive correlation between the M-P-R Receptive Language domain and the PLS-4 Auditory Comprehension subscale. The Cognitive domain of the M-P-R showed a medium positive correlation with later WISC-4 scores, showing acceptable predictive validity. Cognitive strengths and weaknesses assessed using the M-P-R mirrored those described for other measures, with most children obtaining higher standard scores on the Cognitive than the Receptive Language domain. An exploratory factor analysis suggested that one factor accounted for the majority of variability in M-P-R domains.


Inhibition of human muscle-specific enolase by methylglyoxal and irreversible formation of advanced glycation end products.
Methylglyoxal (MG) was studied as an inhibitor and effective glycating factor of human muscle-specific enolase. The inhibition was carried out by the use of a preincubation procedure in the absence of substrate. Experiments were performed in anionic and cationic buffers and showed that inhibition of enolase by methylglyoxal and formation of enolase-derived glycation products arose more effectively in slight alkaline conditions and in the presence of inorganic phosphate. Incubation of 15 micromolar solutions of the enzyme with 2 mM, 3.1 mM and 4.34 mM MG in 100 mM phosphate buffer pH 7.4 for 3 h caused the loss a 32%, 55% and 82% of initial specific activity, respectively. The effect of MG on catalytic properties of enolase was investigated. The enzyme changed the K(M) value for glycolytic substrate 2-phospho-D-glycerate (2-PGA) from 0.2 mM for native enzyme to 0.66 mM in the presence of MG. The affinity of enolase for gluconeogenic substrate phosphoenolpyruvate altered after preincubation with MG in the same manner, but less intensively. MG has no effect on V(max) and optimal pH values. Incubation of enolase with MG for 0-48 h generated high molecular weight protein derivatives. Advanced glycation end products (AGEs) were resistant to proteolytic degradation by trypsin. Magnesium ions enhanced the enzyme inactivation by MG and facilitated AGEs formation. However, the protection for this inhibition in the presence of 2-PGA as glycolytic substrate was observed and AGEs were less effectively formed under these conditions.


Control of plant trichome development by a cotton fiber MYB gene.
Cotton (Gossypium spp) plants produce seed trichomes (cotton fibers) that are an important commodity worldwide; however, genes controlling cotton fiber development have not been characterized. In Arabidopsis thaliana the MYB gene GLABRA1 (GL1) is a central regulator of trichome development. Here, we show that promoter of a cotton fiber gene, RD22-like1 (RDL1), contains a homeodomain binding L1 box and a MYB binding motif that confer trichome-specific expression in Arabidopsis. A cotton MYB protein GaMYB2/Fiber Factor 1 transactivated the RDL1 promoter both in yeast and in planta. Real-time PCR and in situ analysis showed that GaMYB2 is predominantly expressed early in developing cotton fibers. After transferring into Arabidopsis, GL1::GaMYB2 rescued trichome formation of a gl1 mutant, and interestingly, 35S::GaMYB2 induced seed-trichome production. We further demonstrate that the first intron of both GL1 and GaMYB2 plays a role in patterning trichomes: it acts as an enhancer in trichome and a repressor in nontrichome cells, generating a trichome-specific pattern of MYB gene expression. Disruption of a MYB motif conserved in intron 1 of GL1, WEREWOLF, and GaMYB2 genes affected trichome production. These results suggest that cotton and Arabidopsis use similar transcription factors for regulating trichomes and that GaMYB2 may be a key regulator of cotton fiber development.


Clinicians' perceptions of boundaries in Brazil and the United States.
Although there has been considerable discussion of boundary excursions in clinician-patient relationships, little empirical research exists. This pilot study adds to the existing theoretical discussion by comparing perceptions by mental health professionals in Brazil and the United States of what may constitute boundary violations. Participants rated each possible boundary violation according to its degree of harm and professional unacceptability. Three distinct groupings of boundary violations were found: (1) core, consisting of the most serious violations; (2) separation of therapist and client lives, involving encounters between therapists and clients outside of therapy; and (3) disclosure and greeting behavior, involving disclosure of information about the therapist and greeting behavior. The U.S. and Brazilian perceptions were found to be surprisingly similar, with only a few differences.


Large-scale calculations of thermoelectric transport coefficients: a case study of γ-graphyne with point defects.
Defects such as vacancies and impurities could have profound effects on the transport properties of thermoelectric materials. However, it is usually quite difficult to directly calculate the thermoelectric properties of defect-containing systems via first-principles methods since a very large supercell is required. In this work, based on the linear response theory and the kernel polynomial method, we present an efficient approach that can help to calculate the thermoelectric transport coefficients of a large system containing millions of atoms at arbitrary chemical potential and temperature. As a prototype example, we consider dilute vacancies and hydrogen impurities in a large-scale γ-graphyne sheet and discuss their effects on the thermoelectric transport properties.


A comparison of rat chronic progressive nephropathy with human renal disease-implications for human risk assessment.
Chronic progressive nephropathy (CPN) is a single renal disease of unknown etiology, occurring in high incidence in laboratory rats, that can confound subchronic and carcinogenicity bioassay interpretation. It has effects on longevity and, in its early stages, it has a histological similarity to tubular degeneration from other causes. In its advanced stages it is associated with marginally increased renal tubule tumor incidences. Several natural or physiological factors influence its incidence and severity, most prominently protein and caloric intake and male sex hormones. By contrast, there is no entity in humans that presents with the combination or pattern of histological features found in rat CPN. Humans are affected by several different nephropathies of known etiology but generally these are found much less frequently than CPN is found in the rat. There are major differences in pathology between CPN and human nephropathies. Histological characteristics in CPN include prominently dilated tubules filled with proteinaceous casts with consequent kidney enlargement, which contrasts with the shrunken kidneys found in end-stage human nephropathy. Unlike human nephropathy, CPN is devoid of vascular changes, it has no immunological or autoimmune basis, and inflammation is not a prominent feature. Various chemicals exacerbate CPN; no equivalent chemical interactions are seen with human nephropathies. Because some chemicals exacerbate CPN, and advanced CPN is a small risk factor for renal tubule tumor development, an increase in renal tumors can be wrongly attributed to a direct chemical effect on the kidney. On the basis of differences in biology and pathology, this analysis concludes that there is no clear human counterpart of CPN. We recommend that chemically induced exacerbation of CPN not be acknowledged as an indicator of human toxic hazard. Increases in the incidence of CPN-related renal tumor is not considered relevant to humans.


Treatment of chronic iron overload.
The clinical features and therapy of chronic iron overload are reviewed. Chronic iron overload is classified as primary or secondary hemochromatosis. In primary hemochromatosis a genetic defect in iron metabolism results in increased absorption of iron from the gastrointestinal tract. The excess iron in secondary hemochromatosis may be derived from increased gastrointestinal absorption due to ineffective erythropoiesis or from medicinal, dietary, or transfusional sources. Phlebotomy is the treatment of choice in patients with primary hemochromatosis. Iron chelation therapy is indicated in patients who are not candidates for phlebotomy. Deferoxamine mesylate, the only commercially available iron chelator, is usually administered subcutaneously or intravenously over 10-12 hours/day. Serum ferritin concentrations are measured every three to six months to monitor the effectiveness of therapy. The adverse effects of deferoxamine include local skin reactions, ototoxicity, cataracts, growth impairment, and increased susceptibility to infectious organisms. Patient compliance may be compromised by the routes of administration and cost of deferoxamine. Early detection and prompt treatment are necessary to prevent organ damage. Phlebotomy and iron chelation therapy are effective in the treatment of chronic iron overload.


Specific binding of leukotriene B4 to a receptor on human polymorphonuclear leukocytes.
In this paper we have described the binding of nanomoler concentrations of [3H]leukotriene B4 (LTB4) to human polymorphonuclear leukocytes. Because up to 80% of the total [3H]LTB4 binding was blocked by excess (greater than 100 times) [14C]LTB4, the majority of binding is specific. Stereospecificity of the LTB4 binding is demonstrated by the diminished relative abilities of the 6-trans-and 12-epi-6-trans- isomers of LTB4 to block [3H]LTB4 binding. With these two isomers 3-10-fold higher than [14C]LTB4 concentrations were needed for equivalent inhibition of [3H]LTB4 binding. This difference is quantitatively less dramatic than the differences between these isomers in many in vitro functional assays such as chemokinesis, chemotaxis, and degranulation. Binding of [3H]FMLP is not blocked at greater than 100-fold excess of LTB4. The binding of [3H]LTB4 to cells appears to be essentially irreversible at 4 degrees C, but not at 37 degrees C where initially bound LTB4 is rapidly converted to metabolites which then enter the medium. These results suggest the presence of a saturable, stereospecific site for LTB4 on PMN. The association of LTB4 binding and the initiation of pharmacological responses to LTB4 will require further studies.


Effects of learning for linear and differential video magnifiers.
This study sought to determine the learning effects of repeated practice with the traditional linear and the novel differential linear and differential non-linear magnification methods on visual inspection performance. Performance feedback of speed and accuracy and process feedback of scan paths and coverage of search area were given to subjects in order to facilitate the learning process. Objective performance in terms of speed and accuracy and subjective evaluation using the NASA Task Load Index paradigm were captured and analysed. The results showed that there were positive learning effects for the three magnification methods and the learning effects for the two differential magnification methods were greater than that for the traditional linear method. Three exponential learning curves were established for the three search tasks, which showed that search performance with the differential linear and differential non-linear magnifications would surpass the traditional linear method after four and 10 sessions of repeated practice, respectively.


Natural killer cell developmental pathways: a question of balance.
NK cells sit at the crossroads of innate and adaptive immunity and help coordinate tumor immunosurveillance and the immune response against pathogens. Balancing signals to NK cell precursors is crucial for their early development, when transcription factors compete to specify the different lymphocyte subsets. Despite an elaborate schema for NK cell development and differentiation, several major issues remain to be addressed, such as identifying the sites for NK cell maturation and defining the peripheral NK cell niche.


Liver segmentation and metastases detection in MR images using convolutional neural networks.
Primary tumors have a high likelihood of developing metastases in the liver, and early detection of these metastases is crucial for patient outcome. We propose a method based on convolutional neural networks to detect liver metastases. First, the liver is automatically segmented using the six phases of abdominal dynamic contrast-enhanced (DCE) MR images. Next, DCE-MR and diffusion weighted MR images are used for metastases detection within the liver mask. The liver segmentations have a median Dice similarity coefficient of 0.95 compared with manual annotations. The metastases detection method has a sensitivity of 99.8% with a median of two false positives per image. The combination of the two MR sequences in a dual pathway network is proven valuable for the detection of liver metastases. In conclusion, a high quality liver segmentation can be obtained in which we can successfully detect liver metastases.


Syndecan-3 and Notch cooperate in regulating adult myogenesis.
Skeletal muscle postnatal growth and repair depend on satellite cells and are regulated by molecular signals within the satellite cell niche. We investigated the molecular and cellular events that lead to altered myogenesis upon genetic ablation of Syndecan-3, a component of the satellite cell niche. In the absence of Syndecan-3, satellite cells stall in S phase, leading to reduced proliferation, increased cell death, delayed onset of differentiation, and markedly reduced numbers of Pax7(+) satellite cells accompanied by myofiber hypertrophy and an increased number of centrally nucleated myofibers. We show that the aberrant cell cycle and impaired self-renewal of explanted Syndecan-3-null satellite cells are rescued by ectopic expression of the constitutively active Notch intracellular domain. Furthermore, we show that Syndecan-3 interacts with Notch and is required for Notch processing by ADAM17/tumor necrosis factor-alpha-converting enzyme (TACE) and signal transduction. Together, our data support the conclusion that Syndecan-3 and Notch cooperate in regulating homeostasis of the satellite cell population and myofiber size.


Effects of some metals on carbonic anhydrase from brains of rainbow trout.
Carbonic anhydrase (CA) enzyme was purified from rainbow trout brain by Sepharose-4B-L: -tyrosine-sulfanilamide affinity chromatography. The enzyme was obtained with a specific activity of 2,275 EU mg(-1) and a yield of 22.5%. The sample obtained from the affinity column was used for kinetic properties and inhibition studies. Both optimum and stable pH were found as 9.0 in 1 M Tris-SO(4) at 4 degrees C, respectively. To check the purity and subunit molecular weight of enzyme, sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis was performed, and MW was found as approximately 29.0 kDa. The molecular weight of native enzyme was estimated to be approximately 27.3 kDa by gel filtration chromatography. The purified enzyme had apparent K (m),V (max), and k (cat) as follows: 0.92 mM, 0.207 micromol.min(-1) and 43.6 s(-1) for p-nitrophenylacetate. The inhibitory effects of Co(II), Cu(II), Zn(II), Ag(I), and Cd(II) on CA enzyme activity were determined using the esterase method under in vitro conditions at low concentrations of the corresponding metals. The obtained IC(50) values, which cause 50% inhibition on in vitro enzyme activity, were 0.05, 30, 0.31, 159, and 82.5 mM for cobalt, copper, zinc, silver, and cadmium, respectively. K ( i ) values were also calculated from Linewaever-Burk plots for these substances as 0.014, 27.68, 2.15, 193.86, and 94.18 for cobalt, copper, zinc, silver, and cadmium, respectively; it was determined that cobalt, silver and cadmium inhibited the enzyme competitively, copper inhibited noncompetitively while zinc inhibited the enzyme uncompetitively.


Association Between Herpes Simplex Virus II Infection and Rheumatoid Arthritis in US Adults: A Population-Based Propensity Score-Matching Study.
The potential correlation between herpes simplex virus (HSV) and human papillomavirus (HPV) infections and rheumatoid arthritis (RA) has not been definitively established. Further research is needed to determine the relationship between the development of RA and the presence of these viral infections. A retrospective case-control study was conducted with data from the National Health and Nutrition Examination Survey between 2009 and 2014. Our analysis examined the association between HSV I, HSV II, HPV oral polymerase chain reaction (PCR), HPV vaginal PCR, and RA. We identified adults aged 20 to 49 years with a primary diagnosis of RA using the National Health and Nutrition Examination Survey database codes (MCQ191 = 1 [years 2009-2010]; MCQ195 = 2 [years 2011-2014]) and excluded patients with incomplete data on key variables and primary outcomes. The study included 8620 patients, with 150 patients diagnosed with RA and 1500 patients without RA. Patients with RA had a significantly higher prevalence of HSV II infection compared with those without RA (36.34% vs. 24.72%, p = 0.015) after propensity score matching. No significant differences were observed for HSV I, HPV oral PCR, and HPV vaginal PCR between the 2 groups. Patients with RA were older; were more likely to be female, obese, and non-Hispanic White; and had a higher prevalence of comorbidities than those without RA. This population-based propensity score-matching study provides evidence of an association between HSV II infection and RA in US adults. Further research is needed to fully elucidate the relationship between viral infections and RA, with the aim of developing effective risk reduction strategies and innovative treatments for RA.


The mutagenicity of sodium bisulfite on base-substitution strains of Salmonella typhimurium.
The mutagenic effects of sodium bisulfite on Salmonella typhimurium LT2 strains carrying the hisG46 allele were investigated. Treating the cells with 1 M sodium bisulfite in 0.2 M acetate buffer (pH 5.2) for various time intervals at 37 degrees C resulted in an increase in the yield of mutants above the spontaneous level. The fold enhancement of the mutant yield and the fold enhancement of the mutant frequency were greatest for the parent strain hisG46 with wild type DNA repair; the derived strains with reduced repair capacity responded to a lesser degree. While sodium bisulfite was mutagenic when tested in liquid suspension assays, strain hisG46 did not respond when the standard Ames plate incorporation assay was used. The greater mutagenic response in repair-proficient strains suggests that normal repair capacities may favor the mutagenic activity of sodium bisulfite. Transduction studies demonstrated that mutations of his+ were closely linked to the hisD gene, and probably were in the structural hisG gene itself.


Differentiation-state plasticity is a targetable resistance mechanism in basal-like breast cancer.
Intratumoral heterogeneity in cancers arises from genomic instability and epigenomic plasticity and is associated with resistance to cytotoxic and targeted therapies. We show here that cell-state heterogeneity, defined by differentiation-state marker expression, is high in triple-negative and basal-like breast cancer subtypes, and that drug tolerant persister (DTP) cell populations with altered marker expression emerge during treatment with a wide range of pathway-targeted therapeutic compounds. We show that MEK and PI3K/mTOR inhibitor-driven DTP states arise through distinct cell-state transitions rather than by Darwinian selection of preexisting subpopulations, and that these transitions involve dynamic remodeling of open chromatin architecture. Increased activity of many chromatin modifier enzymes, including BRD4, is observed in DTP cells. Co-treatment with the PI3K/mTOR inhibitor BEZ235 and the BET inhibitor JQ1 prevents changes to the open chromatin architecture, inhibits the acquisition of a DTP state, and results in robust cell death in vitro and xenograft regression in vivo.


Non-monotonic health behaviours - implications for individual health-related behaviour in a demand-for-health framework.
A number of behaviours influence health in a non-monotonic way. Physical activity and alcohol consumption, for instance, may be beneficial to one's health in moderate but detrimental in large quantities. We develop a demand-for-health framework that incorporates the feature of a physiologically optimal level. An individual may still choose a physiologically non-optimal level, because of the trade-off in his or her preferences for health versus other utility-affecting commodities. However, any deviation above or below the physiologically optimal level will be punished with respect to health. Distinguishing between two individual types we study (a) the qualitative properties of optimal time-paths of health capital and health-related behaviour, (b) the perturbations of the optimal time-paths that result from changes in exogenous parameters, and (c) steady state properties. Predictions of the model and the implications for empirical analysis are discussed at length. Some comments on potential future extensions conclude the paper.


Long-term outcomes of combining prostate brachytherapy and metastasis-directed radiotherapy in newly diagnosed oligometastatic prostate cancer: A retrospective cohort study.
Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) trial showed the survival benefit for prostate radiotherapy in newly diagnosed prostate cancer patients with a low metastatic burden. The result raises the next question whether additional radiotherapy to metastatic sites could improve the survival in those with a low metastatic burden. We evaluated the efficacy and safety of prostate-directed radiotherapy (PDRT) with or without metastasis-directed radiotherapy (MDRT) in newly diagnosed oligometastatic patients who underwent combination of high-dose-rate prostate brachytherapy, external beam radiotherapy, and androgen deprivation therapy. Forty patients with bone metastasis and node positive prostate cancer were retrospectively analyzed. Of these, 22 (55%), 3 (7%), and 15 (38%) patients had N1M0, M1a, and M1b, respectively. Eighteen patients (45%) received MDRT to all metastatic sites. All patients initially underwent ≧6 months of androgen deprivation therapy. Oligometastatic disease was defined as presence of five or fewer metastatic lesions. Median follow-up period was 62.5 months. Of the 40 patients, the 5-year castration-resistant prostate cancer (CRPC)-free survival rate and cancer-specific survival was 64.4% and 87.9%, respectively. Pre- or post-treatment predictive value including prostate-specific antigen (PSA) at diagnosis ≥20 ng/mL, Gleason grade group 5, positive biopsy core rate ≥51%, PSA nadir level of ≥0.02 ng/mL after the radiotherapy, and no MDRT were significantly associated with progression to CRPC. Patients with MDRT had significantly higher probability of achieving a PSA level of <0.02 ng/mL than those without the therapy (88.8% vs 54.5%, P = 0.0354) and consequently had a better CRPC-free survival than those without the therapy (HR 0.319, 95%CI: 0.116-0.877). Comparing PDRT alone, PDRT with MDRT did not significantly increase the incidences of genitourinary and gastrointestinal toxicities. This single-institutional study revealed the feasibility of combining prostate brachytherapy and MDRT for newly diagnosed oligometastatic prostate cancer. This combined approach has potential to prolong CRPC-free survival.


Effect of CHRFAM7A Δ2bp gene variant on secondary inflammation after spinal cord injury.
The α7 neuronal nicotinic acetylcholine receptors (α7nAChRs) are essential for anti-inflammatory responses. The human-specific CHRFAM7A gene and its 2bp deletion polymorphism (Δ2bp variant) encodes a structurally-deficient α7nAChRs that may impact the anti-inflammatory function. We studied 45 spinal cord injury (SCI) patients for up to six weeks post SCI to investigate the role of the Δ2bp variant on multiple circulating inflammatory mediators and two outcome measures (neuropathic pain and risk of pressure ulcers). The patient's SCI were classified as either severe or mild. Missing values were imputed. Overall genetic effect was conducted with independent sample t-test and corrected with false discovery rate (FDR). Univariate analysis and regression analysis were applied to evaluate the Δ2bp effects on temporal variation of inflammatory mediators post SCI and their interaction with outcome measures. In severe SCI, the Δ2bp carriers showed higher levels of circulating inflammatory mediators than the Δ2bp non-carriers in TNF-α (FDR = 9.6x10-4), IFN-γ (FDR = 1.3x10-3), IL-13 (FDR = 1.6x10-3), CCL11 (FDR = 2.1x10-3), IL-12p70 (FDR = 2.2x10-3), IL-8 (FDR = 2.2x10-3), CXCL10 (FDR = 3.1x10-3), CCL4 (FDR = 5.7x10-3), IL-12p40 (FDR = 7.1x10-3), IL-1b (FDR = 0.014), IL-15 (FDR = 0.024), and IL-2 (FDR = 0.037). IL-8 and CCL2 were negatively associated with days post injury (DPI) for the Δ2bp carriers (P = 2x10-7 and P = 2x10-8, respectively) and IL-5 was positively associated with DPI for the Δ2bp non-carriers (P = 0.015). Neuropathic pain was marginally positively associated with IL-13 for the Δ2bp carriers (P = 0.056). In mild SCI, the Δ2bp carriers had lower circulating levels of IL-15 (FDR = 0.04) than the Δ2bp non-carriers. Temporal variation of inflammatory mediators post SCI was not associated with the Δ2bp variant. For the mild SCI Δ2bp carriers, risk of pressure ulcers was positively associated with circulating levels of IFN-γ, CXCL10, and CCL4 and negatively associated with circulating levels of IL-12p70. These findings support an important role for the human-specific CHRFAM7A Δ2bp gene variant in modifying anti-inflammatory function of α7nAChRs following SCI.


A novel clade of protistan parasites near the animal-fungal divergence.
Sequences of nuclear-encoded small-subunit rRNA genes have been determined for representatives of the enigmatic genera Dermocystidium, Ichthyophonus, and Psorospermium, protistan parasites of fish and crustaceans. The small-subunit rRNA genes from these parasites and from the "rosette agent" (also a parasite of fish) together form a novel, statistically supported clade. Phylogenetic analyses demonstrate this clade to diverge near the animal-fungal dichotomy, although more precise resolution is problematic. In the most parsimonious and maximally likely phylogenetic frameworks inferred from the most stably aligned sequence regions, the clade constitutes the most basal branch of the metazoa; but within a limited range of model parameters, and in some analyses that incorporate less well-aligned sequence regions, an alternative topology in which it diverges immediately before the animal-fungal dichotomy was recovered. Mitochondrial cristae of Dermocystidium spp. are flat, whereas those of Ichthyophonus hoferi appear tubulovesiculate. These results extend our understanding of the types of organisms from which metazoa and fungi may have evolved.


Determination of the transfer function of an atmospheric pressure drift tube ion mobility spectrometer for nanoparticle measurements.
Drift tube-ion mobility spectrometers (DT-IMSs) are used to separate and characterize the structures of gas phase ions. Recent work in coupling an atmospheric pressure DT-IMS to a condensation particle counter (CPC) has extended the application of drift tube ion mobility spectrometry to nanoparticle analysis, with measurements possible for singly charged particles up to 20 nm in diameter. In examining systems with such large analytes, often of interest is not only separation, but also determination of the nanoparticle size or mobility distribution function, defined as the nanoparticle concentration per unit mobility/size. Distribution function determination requires a priori knowledge of the DT-IMS transfer function, i.e. the DT-IMS combined transmission and detection efficiency as a function of both mobility and drift/arrival time. The transfer function completely describes analyte transport through an instrument; unfortunately, it has not been experimentally determined in previous work for a DT-IMS. Here, we develop and apply a new method to infer the transfer function of a DT-IMS-CPC system, wherein the system is used to measure particles which are first transmitted through a well-characterized differential mobility analyzer (DMA). The DMA acts as a mobility filter, and only transmits particles within a narrow, well-defined mobility range. From a series of measurements at fixed drift/arrival time (up to 12 seconds) but variable DMA transmission window, DT-IMS-CPC transfer functions are inverted via a Twomey-Markowski algorithm. Transfer function inversion reveals that the DT-IMS-CPC system has a resolving power in excess of 10 and upwards of 20. Such resolving powers are in good agreement with model predictions, and are higher than commercially available DMAs in the nanoparticle size range.


Monitoring biofilm formation by using cyclic voltammetry-effect of the experimental conditions on biofilm removal and activity.
The effect of experimental conditions on cyclic voltammetry experiments on platinum electrodes covered with biofilms formed by Pseudomonas fluorescens for 2 hours was investigated. Results show that recycling the potential stabilizes the shape of the cyclic voltammogram after 195 cycles, but the observation of the electrodes by epifluorescence microscopy showed that cells are still adhered to the platinum surface. Some experimental conditions were changed during the electrochemical measurements--sweep rate, pH of the buffer and applied potential range. Some of these parameters had a strong impact on the bacteria that are adhered to the surface, increasing the death and removal in some circumstances.


Antioxidant activity of polyphenols from green and toasted mate tea.
The production and distribution of toasted mate tea in Brazil has increased, which has resulted in its greater consumption. Mate tea is obtained by roasting non-fermented erva-mate in order to produce toasted erva-mate or toasted mate tea. However, although the product is much appreciated, studies of its chemical composition and the concentration of polyphenols, particularly flavonols present in toasted mate tea, are few and often controversial. This paper elucidates some misunderstandings involving the nomenclature of erva-mate and toasted mate, and mainly provides an overview of the composition of polyphenols and antioxidant capacity of toasted mate tea and its raw material, erva-mate, in comparison with other teas, the compositions of which were found in the literature.


Electrospun Cactus Mucilage/Poly(vinyl alcohol) Nanofibers as a Novel Wall Material for Dill Seed Essential Oil (Anethum graveolens L.) Encapsulation: Release and Antibacterial Activities.
This study aimed to create long-lasting carriers by producing electrospun nanofibers loaded with dill seed (Anethum graveolens L.) essential oil (DSEO), using cactus mucilage (CM) and poly(vinyl alcohol) (PVA). Continuous and uniform electrospun nanofibers with a diameter of 158 ± 18 to 230 ± 26 nm were successfully made from the CM/PVA blend solution and the CM/PVA/DSEO emulsion. Atomic force microscopy topographic images revealed that the electrospun nanofibers had a tubular morphology. The thermogravimetric curves of DSEO, CM, pure PVA, and electrospun nanofibers demonstrate that the polymers used and the essential oil have effective chemical interactions. The water contact angle results suggest that the manufactured nanofibers are hydrophilic. CM/PVA consistently achieves a remarkable encapsulation efficiency of 100% DSEO. The electrospun nanofibers enabled the controlled release of free and encapsulated DSEO, resulting in sustained long-term release. The agar disk diffusion technique was used to study the antimicrobial activity of electrospun nanofibers and nanofibers containing DSEO against Gram-positive and Gram-negative bacteria. With a minimum inhibitory concentration of 2.5 mg/mL and a minimum bactericidal concentration of 5 mg/mL, electrospun nanofibers containing DSEO demonstrated bacteriostatic and bactericidal activities against foodborne pathogenic bacteria (Staphylococcus aureus and Pseudomonas aeruginosa). The DSEO-loaded electrospun nanofibers derived from carbohydrates show promise as an active interior coating for use in biomedical and food packaging applications.


The preparation and properties of yeast beta-fructofuranosidase chemically attached to polystyrene.
1. A process is described for the chemical attachment of an enzyme to the surface of a polystyrene matrix. 2. By this process yeast beta-fructofuranosidase was chemically attached to the surface of both polystyrene beads and polystyrene tubes. 3. The kinetics of sucrose hydrolysis by beta-fructofuranosidase and polystyrene-supported beta-fructofuranosidase were compared. 4. The pH-activity curve of the polystyrene-supported enzyme shows a marked difference from that of the free enzyme in solution. 5. The inhibitor dissociation constant with respect to tris is increased, whereas the inhibitor dissociation constant with respect to aniline is decreased when the enzyme is attached to polystyrene. 6. Differences between the properties of the bound and free enzyme are discussed in terms of a micro-environmental effect arising from the hydrophobic nature of the polystyrene support.


Termination of twin gestation by blastocyst crush in the broodmare.
Manual crushing of one blastocyst performed on 181 bicornuate twin pregnancies between Days 24 and 45 has shown that the uncrushed blastocyst can either survive and develop normally to full term or may be rejected and resorbed like its crushed twin, depending mainly on the stage of pregnancy. Crushing, which causes rupture of fetal membranes, results in a rapid fall in the survival rate of the uncrushed blastocyst when performed after Day 31. In some mares rupture is not possible after Day 35 even if extreme pressure is used. Crushed, but unruptured, blastocysts mainly between Days 35 and 45 may (a) resorb as does the uncrushed twin (60%) (b) resorb without loss of the uncrushed twin (20%) or (c) survive, as does the uncrushed twin, even when several attempts on alternate days are made to destroy the blastocyst (20%). At no stage of pregnancy is the uncrushed embryo resorbed unless the crushed twin is destroyed. The rejection and resorption of the uncrushed twin is not due to transference of pressure, but presumably to physiological processes involving prostaglandin. Mefenamic acid appears to increase survival rates especially when crushing is performed after 31 days, although the twin of apparently successful crushings at this stage may be lost between Days 50 and 70.


Trapping a 96 degrees domain rotation in two distinct conformations by engineered disulfide bridges.
Engineering disulfide bridges is a common technique to lock a protein movement in a defined conformational state. We have designed two double mutants of Escherichia coli 5'-nucleotidase to trap the enzyme in both an open (S228C, P513C) and a closed (P90C, L424C) conformation by the formation of disulfide bridges. The mutant proteins have been expressed, purified, and crystallized, to structurally characterize the designed variants. The S228C, P513C is a double mutant crystallized in two different crystal forms with three independent conformers, which differ from each other by a rotation of up to 12 degrees of the C-terminal domain with respect to the N-terminal domain. This finding, as well as an analysis of the domain motion in the crystal, indicates that the enzyme still exhibits considerable residual domain flexibility. In the double mutant that was designed to trap the enzyme in the closed conformation, the structure analysis reveals an unexpected intermediate conformation along the 96 degrees rotation trajectory between the open and closed enzyme forms. A comparison of the five independent conformers analyzed in this study shows that the domain movement of the variant enzymes is characterized by a sliding movement of the residues of the domain interface along the interface, which is in contrast to a classical closure motion where the residues of the domain interface move perpendicular to the interface.