Assuring a Continuum of Care for Heart Failure Patients Through Postacute Care Collaboration: An Integrative Review.
This review evaluates the published studies on how postacute care collaboration ensures a continuum of care and reduces heart failure (HF) readmissions. An integrated literature review was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Statement. PubMed and Cumulative Index to Nursing and Allied Health were searched for the keywords heart failure AND (post-acute care OR transitional care OR skilled nursing facility OR rehabilitation facility OR home health agency) AND (readmission) AND (care coordination OR collaboration OR interprofessional OR partnerships). Seventy-nine studies were returned, and a reverse reference search yielded four studies. Of those studies, 14 were selected for critical appraisal of evidence. The practice settings of these studies were hospitals, homes, home health agencies, and skilled nursing facilities. Multidisciplinary management of HF patients, high-impact transitional care interventions, and integration with postacute care facilities decreased HF 30-day readmissions. Collaborative models involving a skilled HF team, primary care physicians, and postacute care partners, and targeting postdischarge follow-ups positively impacted outcomes. Bundling interventions, such as home visits, follow-ups (telephone and/or clinic follow-up), and telecare, significantly impacted outcomes compared with their delivery in isolation. Case management leaders are vital decision-makers and key stakeholders in building the collaboration with community partners. As case management roles extend to outpatient and ambulatory care, better opportunities emerge to coordinate services across settings. Key takeaways for the case management practice is to build a robust case management program spanning postacute care facilities, evidence-based treatment protocols, and infrastructure that supports seamless information sharing between sites.


Vascular contractile effect of urotensin II in young and aged rats: influence of aging and contribution of endothelial nitric oxide.
To elucidate whether aging influences the vascular contractile effect of urotensin II in rat thoracic aorta, and to evaluate the contribution of endothelial vasodilating substances in mediating the effect of urotensin II, the effect of urotensin II was examined in the vessels of young (2-3-month-old) and aged rat. Isolated rat aortic rings incubated in Krebs-Henseleit solution gassed with 95% O2/5% CO2 were stimulated with urotensin II, and the developed tension was measured. Urotensin II increased the developed tension, which was decreased by aging. In 2-3-months-old young aorta without endothelium, urotensin II (10(-10) to 10(-7)) elicited a concentration-dependent aortic contraction to the maximal response almost equivalent to high KCl-induced contraction (79.4+/-11.3% of KCl(max)). In the presence of endothelium, the urotensin II-induced vasoconstriction in young aorta was significantly attenuated to 33.3+/-4.6% of KCl(max). However, the contractile response was greater in the pretreatment with N(G)-nitro-L-arginine (L-NNA) (100 microM) (50.3+/-8.4% of KCl(max) in endothelial denuded aorta), suggesting the vasorelaxing role of endothelial nitric oxide. In 25-27-months-old aged rat aorta, the urotensin II-mediated contraction was remarkably decreased, both in the presence (6.3+/-2.0% of KCl(max)) and absence (11.7+/-3.0% of KCl(max)) of endothelium. A cyclooxygenase inhibitor, diclofenac (10 microM), did not have any effect on the urotensin II-induced contraction. These results suggest that urotensin II can induce vascular smooth muscle contraction in rat aorta, and there was an aging-related decline in the urotensin II-induced contraction. Endothelial production of nitric oxide in response to urotensin II but not cyclooxygenase metabolites such as prostacyclin may play a role in reducing the vascular constriction especially in young aorta.


Pharmacokinetics and pharmacodynamics of terfenadine and chlorpheniramine in the elderly.
In a double-blind, randomized, crossover study, the H1-receptor antagonists, terfenadine and chlorpheniramine, were investigated in eight healthy, fasting female subjects, aged 67.8 +/- SD 0.8 years, who ingested single doses of terfenadine, 1 mg/kg (mean dose, 69.6 +/- 11.2 mg), and chlorpheniramine, 0.12 mg/kg (mean dose, 8.4 +/- 1.3 mg). The mean serum-elimination half-life of terfenadine metabolite I was 8.7 +/- 3.7 hours. After terfenadine ingestion, significant wheal suppression occurred from 2 to 24 hours compared to predose wheal size, with maximum wheal suppression, 42 +/- 13% to 60 +/- 16% from 2 to 12 hours. Significant flare suppression occurred from 2 to 24 hours, with maximum flare suppression, 75 +/- 15% to 78 +/- 13% from 4 to 8 hours. The mean serum-elimination half-life of chlorpheniramine was 22.6 +/- 11.0 hours. After chlorpheniramine ingestion, significant wheal suppression occurred from 1 to 10 hours, inclusive, compared to predose wheal size, with maximum wheal suppression, 36 +/- 11% to 37 +/- 11% from 5 to 6 hours. Significant flare suppression occurred from 1 to 12 hours, with maximum flare suppression of 43 +/- 14% to 46 +/- 19% at 2, 5, and 6 hours (p less than 0.01). Adverse effects, chiefly sedation, occurred in five of eight patients after receiving terfenadine, and in all eight patients after receiving chlorpheniramine; but, since no placebo control was administered, these adverse effects could not be definitely attributed to H1-receptor-antagonist ingestion.


Periodontal disease and preterm birth.
Preterm birth (delivery at fewer than 37 weeks' gestation) is the most common cause of infant morbidity and mortality among nonanomalous infants in the United States. Increasing evidence has focused on associations between clinical infection, inflammation, and preterm birth. Maternal periodontal disease, which is associated with systemic inflammation, has been associated with preterm birth. Intervention trails for treatment of periodontal disease during pregnancy, however have not consistently shown a reduction in preterm birth rates. Despite the lack of reduction in preterm birth, oral health maintenance is an important part of preventive care and should be supported during pregnancy.


Do responses to the COVID-19 pandemic anticipate a long-lasting shift towards peer-to-peer production or degrowth?
The COVID-19 pandemic simultaneously triggered a sudden, substantial increase in demand for items such as personal protection equipment and hospital ventilators whilst also disrupting the means of mass-production and international transport in established supply chains. Furthermore, under stay-at-home orders and with bricks-and-mortar retailers closed, consumers were also forced to adapt. Thus the pandemic offers a unique opportunity to study shifts in behaviour during disruption to industrialised manufacturing and economic contraction, in order to understand the role peer-to-peer production may play in a transition to long-term sustainability of production and consumption, or degrowth. Here, we analyse publicly-available datasets on internet search traffic and corporation financial returns to track the shifts in public interest and consumer behaviour over 2019 - 2020. We find a jump in interest in home-making and small-scale production at the beginning of the pandemic, as well as a substantial and sustained shift in consumer preference for peer-to-peer e-commerce platforms relative to more-established online vendors. In particular we present two case studies - the home-made facemasks supplied through Etsy, and the decentralised efforts of the 3D printer community - to assess the effectiveness of their responses to the pandemic. These patterns of behaviour are related to new modes of production in line with ecological economics and as such add capacity to a broader prefiguration of degrowth. We suggest an adoption of a new "fourth wave" of DIY culture defined by enhanced resilience and degrowth to continue to add capacity to a prefigurative politic of degrowth.


Are intermediate filaments of vertebrate smooth muscle cells and tonofilaments of epithelial cells identical cell structures?
In epithelial and smooth muscle cells of the urinary bladder of the frog, a class of filaments exists which is partly disintegrated by glycerol treatment and very resistant to potassium solutions of high ionic strength.


Bronchiolitis in infants: do not use bronchodilators.
A Cochrane systematic review of studies including nearly 2000 infants showed that bronchodilators have no proven efficacy in bronchiolitis.


Teaching About Genetics and Sickle Cell Disease In Fifth Grade.
We are grateful to Laura McVittie Gray for her work on the development of the student activities described in this article. This work was made possible by a Science Education Partnership Award (SEPA), Grant Number R25RR020449, from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). Additional support for this SEPA-funded project was provided by Grant Number UL1RR024131-01 from NCRR. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH. A 5-lesson, 5th-grade instructional unit, "Genetics and Sickle Cell Disease," was developed and tested as part of a 40-lesson curriculum entitled SEEK (Science Exploration, Excitement, and Knowledge): A Curriculum in Health and Biomedical Science for Diverse 4th and 5th Grade Students. The genetics lessons include hands-on activities (e.g., DNA extraction from cheek cells), a simulated plant genetics experiment, and a classroom visit by a person with sickle cell disease, as well as by a health care practitioner who works with sickle cell patients or a scientist specializing in genetics. The unit was tested with 82 5th-grade students at public elementary schools in Oakland, CA; 96% were racial and ethnic minorities. The comparison group consisted of 84 5th-grade Oakland students racially/ ethnically, academically, and socio-economically matched to those in the experimental group. Both groups completed a 20-question, multiple-choice pre/posttest covering science concepts, scientific process, lifestyle choices, and careers. The experimental group showed significant improvement on 13 of 20 questions (P<.05, t-tests) and on the test as a whole, whereas the comparison group did not show significant improvement either on any of the questions or on the test as a whole. The experimental group improved on 10 concept questions, 2 scientific process questions, and 1 lifestyle question. Teachers rated the educational value of the unit as 9.5 on a scale from 1 (low) to 10 (high). These results show that genetics and sickle cell disease can be taught successfully in 5th grade, although they are not typically covered at this level.


Oral Conventional Synthetic Disease-Modifying Antirheumatic Drugs with Antineoplastic Potential: a Review.
There is an increasing trend of malignancy worldwide. Disease-modifying antirheumatic drugs (DMARDs) are the cornerstones for the treatment of immune-mediated inflammatory diseases (IMIDs), but risk of malignancy is a major concern for patients receiving DMARDs. In addition, many IMIDs already carry higher background risks of neoplasms. Recently, the black box warning of malignancies has been added for Janus kinase inhibitors. Also, the use of biologic DMARDs in patients with established malignancies is usually discouraged owing to exclusion of such patients in pivotal studies and, hence, lack of evidence. In contrast, some conventional synthetic DMARDs (csDMARDs) have been reported to show antineoplastic properties and can be beneficial for patients with cancer. Among the csDMARDs, chloroquine and hydroxychloroquine have been the most extensively studied, and methotrexate is an established chemotherapeutic agent. Even cyclosporine A, a well-known drug associated with cancer risk, can potentiate the effect of some chemotherapeutic agents. We review the possible mechanisms behind and clinical evidence of the antineoplastic activities of csDMARDs, including chloroquine and hydroxychloroquine, cyclosporine, leflunomide, mycophenolate mofetil, mycophenolic acid, methotrexate, sulfasalazine, and thiopurines. This knowledge may guide physicians in the choice of csDMARDs for patients with concurrent IMIDs and malignancies.


Depression trajectories among older community dwelling adults: Results from the Irish Longitudinal Study on Ageing (TILDA).
This study investigated the role of a large range psychological, attitudinal and health related variables as predictors of depression trajectories amongst older adults over a 4-year time period. Data from three consecutive waves of the TILDA survey of older community dwelling adults aged 50+ in Ireland were combined for analysis. Depression symptom scores were assessed using the Center for Epidemiological Studies- Depression scale (CES-D). Changes in depression scores over three time points were modelled as distinct trajectory classes using group-based trajectory modelling, whilst simultaneously controlling for demographic, attitudinal and health related predictors of these trajectory classes using multinomial regression. Four distinct depression trajectories were identified as (1) a stable low symptom level group (79%), (2) a moderate but deteriorating symptoms group (7.6%), (3) a moderate but improving group (10.1%) and (4) a vulnerable group with consistently high symptoms (3.1%). Multinomial logistic regression indicated that limiting pain, mobility impairments, perceived stress and loneliness predicted membership of the moderate and higher depressive symptom classes. Retirement status and higher reported levels of worry were associated with a greater likelihood of membership of the moderate symptom classes only. Use of the CES-D is open to bias due to subjective nature of respondent reporting. Results concur with previous studies on the development of depression among older people and highlight the key health related and psychological variables that may inform interventions aimed at mitigating risks of developing depression among older adults.


3D Polyaniline Nanofibers Anchored on Carbon Paper for High-Performance and Light-Weight Supercapacitors.
In the field of advanced energy storage, nanostructured Polyaniline (PANI) based materials hold a special place. Extensive studies have been done on the application of PANI in supercapacitors, however, the structure-property relationship of these materials is still not understood. This paper presents a detailed characterization of the novel sodium phytate doped 3D PANI nanofibers anchored on different types of carbon paper for application in supercapacitors. An excellent relationship between the structures and properties of the synthesized samples was found. Remarkable energy storage characteristics with low values of solution, charge transfer and polarization resistance and a specific capacitance of 1106.9 ± 1.5 F g-1 and 779 ± 2.6 F g-1 at current density 0.5 and 10 Ag-1, respectively, was achieved at optimized conditions. The symmetric supercapacitor assembly showed significant enhancement in both energy density and power density. It delivered an energy density of 95 Wh kg-1 at a power of 846 W kg-1. At a high-power density of 16.9 kW kg-1, the energy density can still be kept at 13 Wh kg-1. Cyclic stability was also checked for 1000 cycles at a current density of 10 Ag-1 having excellent retention, i.e., 96%.


Long term review of laparoscopic sacrocolpopexy.
Assessment of long term outcome following laparoscopic sacrocolpopexy. Retrospective follow up study using standardised examination with pelvic organ prolapse quantification system (POP-Q) and questionnaires. A tertiary urogynaecology unit in the North West of England. One hundred and forty consecutive cases who had a laparoscopic sacrocolpopexy at St Mary's Hospital, Manchester, between 1993 and 1999. Women completed questionnaires and were examined in gynaecology clinic or sent postal questionnaires if unable to attend the clinic. Adequacy of vault support and recurrent vaginal prolapse assessed by POP-Q score. Assessment of prolapse, urinary and bowel symptoms and sexual function using questionnaires. One hundred and three women were contacted after a median of 66 months. Sixty-six women were examined and a further 37 women filled in questionnaires only. Recurrent vault prolapse occurred in 4 of the 66 women who were examined. Prolapse had recurred or persisted in 21 of 66 women, with equal numbers of anterior and posterior vaginal wall prolapse. Overall, 81/102 (79%) said that their symptoms of prolapse were 'cured' or 'improved'; 39/103 (38%) still had symptoms of prolapse. For every two women who were cured of their urinary or bowel symptoms, one woman developed worse symptoms. Among the 66 women available for examination laparoscopic sacrocolpopexy provided good long term support of the vault in 92%. Forty-two percent of these women had recurrent vaginal wall prolapse. Despite this, 79% of women felt that their symptoms of prolapse were cured or improved following surgery.


Organization and structure of the Qa genes of the major histocompatibility complex of the C3H mouse: implications for Qa function and class I evolution.
We have determined the structure and organization of the entire Qa family of class I genes from the major histocompatibility complex of the C3H mouse. Restriction maps of overlapping lambda and cosmid clones reveal that there are only five Qak genes: Q1k, Q2k, Q4k, Q10k and a Q5/9 hybrid, presumably generated by unequal homologous recombination. The resulting deletion of Q6-Q9 is consistent with the Qa-2null phenotype of this mouse strain. We have sequenced the Qak genes, and predict that each may encode a class I molecule with a structure comparable with that proposed for the transplantation antigens. Furthermore, these Qa products should be able to bind peptides and interact with appropriate T-cell receptors. Interestingly, in comparing Qak and H-2k sequences, we find limited evidence of interlocus gene conversion between Qa and H-2 loci, suggesting that the Qa genes are not likely to serve as a reservoir of genetic information for the generation of H-2 diversity within this haplotype.


Orthodontic management of the cleft lip and palate patient.
The importance of the dentition and contribution of the orthodontist to the care of cleft patients from infancy to adulthood are presented. Close communication between orthodontists and surgeons is emphasized. The orthodontic treatment plan is developed around the anatomic, functional, and developmental needs of the patient.


Effect of anticipation during unknown or unexpected exercise duration on rating of perceived exertion, affect, and physiological function.
To determine the effect of unknown exercise duration and an unexpected increase in exercise duration on rating of perceived exertion (RPE), affect, and running economy during treadmill running. Sixteen well trained male and female runners completed three bouts of treadmill running at 75% of their peak treadmill running speed. In the first trial, they were told to run for 20 minutes and were stopped at 20 minutes (20 MIN). In another trial, they were told to run for 10 minutes, but at 10 minutes were told to run for a further 10 minutes (10 MIN). In the final trial, they were not told for how long they would be running but were stopped after 20 minutes (unknown, UN). During each of the running bouts, RPE, oxygen consumption (ml/kg/min), heart rate (beats/min), stride frequency (min(-1)), affect scores (arbitrary units), and attentional focus (percentage associative thought scores) were recorded. RPE increased significantly between 10 and 11 minutes in the 10 MIN compared with the 20 MIN and UN trials (p<0.05). The affect score decreased significantly between 10 and 11 minutes in the 10 MIN compared with the 20 MIN trial (p<0.05). Running economy, as measured by oxygen consumption, was significantly lower in the UN compared with the 20 MIN trial from 10 to 19 minutes (p<0.05). The change in RPE between 10 and 11 minutes in the 10 MIN trial suggests that RPE is not purely a measure of physical exertion, as treadmill speed was maintained at a constant pace both before and after the unexpected increase in exercise duration. The associated changes in affect score at similar times in the 10 MIN trial supports the hypothesis that RPE has an affective component.


Synthesis, characterization of amide substituted dexibuprofen derivatives and their spectral, voltammetric and docking investigations for DNA binding interactions.
Three amide derivatives - methyl-2-[2-(4-isobutylphenyl)propanamido]propanoate (Dex-2), methyl 2-[2-(4-isobutylphenyl) propanamido]-3-phenylpropanoate (Dex-3) and methyl 2-[2-(4-isobutylphenyl)-propanamido]-4-methylpentanoate (Dex-4) of dexibuprofen (Dex-1) 2-(4-isobutylphenyl)propanoic acid were synthesized and conformed for structures by physical data and spectral analysis. Further, all the compounds were studied for their binding with ds.DNA through experimental (UV-visible/and fluorescence spectroscopy, cyclic voltammetry) and theoretical (molecular docking) techniques. Spectral and voltammetric responses as well as kinetic and thermodynamic data interpretations at stomach (4.7) and blood (7.4) pH and at human body temperature (37°C) indicated spontaneous interaction of all the compounds with DNA via intercalation and external bindings. The binding constants (Kb) and Gibbs free energy changes (-ΔG) were evaluated greater at pH7.4 attributing comparatively more significant binding of all the compounds with DNA at blood pH. Among all compounds, Dex-4 showed greater binding with DNA at both pH with greater Kb values i.e., {UV-visible: pH 4.7 (2.36×104M-1); pH7.4 (2.42×104M-1), fluorescence: pH4.7 (2.24×104M-1); pH7.4 (2.56×104M-1) and CV: pH4.7 (4.06×104M-1); pH7.4 (4.89×104M-1)}. Binding site size (n) at both pH values was evaluated n≥1 for Dex-2 and Dex-4 which assured intercalation as a major mode of interaction between compounds and DNA. For Dex-1 and Dex-3 (n) was evaluated n≤1 at both pH values and the values n<1 indicated the possibility of binding via groove or electrostatic interactions. Electrochemical processes were found diffusion controlled and diffusion coefficients (Do) for all the compounds - DNA adducts were evaluated lesser than unbound compounds. Docking studies further supported DNA binding evidences obtained from spectral and electrochemical investigations.


Low blood and plasma carnitine levels in children receiving long-term parenteral nutrition.
Total and free carnitine and acylcarnitine concentrations were analyzed in whole blood and plasma in 12 children with a mean age of 68.4 +/- 42.9 months who had received carnitine-free total parenteral nutrition (TPN) for an average of 4 years. The purpose of the study was to see if the children had become carnitine deficient and, if so, whether this correlated with poor lipid clearance. Compared to controls, the TPN-dependent children had significantly decreased concentrations of total and free carnitine in blood (26.6 +/- 9.4 (SD) mumols/L vs. 43.3 +/- 9.1 mumols/L, p less than 0.001, and 17.1 +/- 7.7 mumols/L vs. 35.2 +/- 8.1 mumols/L, p less than 0.001, respectively). Similar results were found in plasma (total carnitine of 19.0 +/- 8.0 mumols/L vs. 41.9 +/- 5.2 mumols/L, p less than 0.001, and free carnitine of 15.7 +/- 7.3 mumols/L vs. 36.1 +/- 5.2 mumols/L, p less than 0.001, respectively). The acylcarnitine concentration in plasma was decreased in the TPN children (3.3 +/- 1.5 mumols/L vs. 5.8 +/- 3.0 mumols/L, p less than 0.01) compared to controls. Despite the low carnitine concentrations, serum triglyceride levels and serum free fatty acid levels were within the normal range. There was no correlation between carnitine concentrations in plasma and serum triglyceride and free fatty acid levels. Our data show that children receiving carnitine-free TPN for many years developed markedly decreased concentrations of carnitine in blood and plasma. However, no adverse effects of the low carnitine levels were found on triglyceride and free fatty acid metabolism under stable conditions.


[Analysis and processing of two-lead ECG signals based on orthogonal synthesizing].
To dig out the potential information in two-lead ECG signals, and discuss a new method of analyzing and processing two-lead ECG signals, viz. Orthogonal Synthesis Cardiogram (OSCG). From a case in MIT-BIH Database, several representative heartbeats were chosen to draw a series of OSCG, and analyses were made quantitatively and qualitatively. All species of OSCG in the case differed greatly in form. The indices picked up such as maximal vector orientation and amplitude of QRS Loop etc. could effectively distinguish all species of heartbeats. Thus gets more characteristics about the heart transformation beat by beat. OSCG is found to be a simple, capable method, suitable for use in manned space flight.


Haptoglobin-related protein as a serum marker in malignant lymphoma.
A novel serum 21 kDa haptoglobin-related protein (Hpr) was investigated in patients with malignant lymphoma, to evaluate its correlation with clinical and histologic features at presentation and its possible role as a tumor marker for patient outcome. One hundred fifty eight serum samples were taken from 88 patients with non-Hodgkin's lymphoma (n=58) and Hodgkin's disease (n=30) at presentation and in the course of follow-up. Sera from 61 healthy volunteers served as normal controls. Serum Hpr levels in the lymphoma patients (median 430x10 u/ml, range 0-4000x10 ) were significantly higher than in the control group (median 68x10 u/ml, range 0-180x10 )(p=0.0001). Higher median Hpr values were detected in patients with advanced disease (p=0.013), "B" symptoms (p=0.029) and in males (p=0.053). There was also a significant correlation between Hpr and erythrocyte sedimentation rate (p=0.028). Serial determinations showed a significant decrease of the initial Hpr values obtained after treatment in 41 patients, 38 of whom achieved complete remission. In the follow-up period additional Hpr measurements were taken from 17 patients. Three of them eventually relapsed, and showed increased Hpr levels at the time of relapse. Hpr levels remained low in 11 of 14 patients who maintained complete remission, and increased in three. In conclusion, serum Hpr is a new serum tumor marker of potential use in the clinical setting of lymphoma.


Clinical approach to the diagnoses of inborn errors of metabolism.
Inborn errors of metabolism (IEMs) are complex relatively uncommon medical conditions resulting in significant morbidity and mortality. Early recognition and implementation of adequate therapeutic measures are of the utmost importance in minimizing morbidity and improving clinical outcome. This article aims to address the basics of IEMs for familiarizing primary care physicians with different types of metabolic disorders, basic diagnostic strategies, newborn screening programs, and appropriate treatment strategies. Advances in diagnostic and therapeutic options are resulting in increasing longevity and improvement in the clinical outcome of many of these patients.


Multi-omics analysis provides insights intro lysine accumulation in quinoa (Chenopodium quinoa Willd.) sprouts.
Lysine, the first limiting essential amino acid, the deficiency of which seriously affects the health of human and animals. In this study, quinoa germination significantly increased the nutrients, especially lysine content. To better understanding the underlying molecular mechanism of lysine biosynthesis, isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics, RNA-sequencing (RNA-Seq) technology and liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) platform-based phytohormones analyses were conducted. Through proteome analyses, a total of 11,406 differentially expressed proteins were identified, which were mainly related to secondary metabolites. The lysine-rich storage globulins and endogenous phytohormones probably contributed the increased lysine content in quinoa during germination. Furthermore, aspartic acid semialdehyde dehydrogenase is essential for lysine synthesis in addition to aspartate kinase and dihydropyridine dicarboxylic acid synthase. Protein-protein interaction analysis indicated lysine biosynthesis is associated with "amino metabolism" and "starch and sucrose metabolism". Above all, our study screens the candidate genes participated in lysine accumulation and explores the factors affected lysine biosynthesis by multi-omics analysis. These information not only paves a foundation for breeding lysine-rich quinoa sprouts but also provides valuable multi-omics resource to explore the characteristic of nutrients during quinoa germination.


Plasma clearances and extractions of four catecholamines in the anesthetized rabbit: the role of amine removal by blood cells.
The purpose of the present study was to compare the plasma kinetics of norepinephrine (NA), epinephrine (A), isoprenaline (ISO), and dopamine (DA) in the anesthetized rabbit. To this end, a mixture of trace amounts of 3H-labeled NA, A, ISO, and DA was infused either into a femoral vein or into the ascending aorta, and the plasma amine clearances (Cl), the fractional amine extractions across the pulmonary (ERp) as well as systemic (ERs) circulation, and the cardiac output of plasma (COp) were determined at steady state of the amine infusion. The values of ERp, ERs, and COp were also used to calculate total-body fractional extractions [ERtot = ERp + ERs(1 - ERp)] and theoretical clearances (Clcalc = ERtot * COp). The four catecholamines differed as to their values of Cl and ERs and even more so with respect to ERp. The Cl was lowest for NA, intermediate for A and ISO, and highest for DA. Statistically significant pulmonary extractions were observed for NA (8.8%) and DA (24.0%), but not for A and ISO. The systemic extraction was lowest for ISO (63%) and highest for DA (75%). Cl values were higher than values of Clcalc and the ratio of Cl/Clcalc increased in the order of NA < A < ISO < DA. In vitro experiments, in which whole rabbit blood was incubated in the presence of added NA, A, ISO, and DA, showed a pronounced ability of blood cells to remove catecholamines from plasma. The four amines rapidly disappeared from plasma at rates increasing in the order of NA < A < ISO < DA.(ABSTRACT TRUNCATED AT 250 WORDS)


Novel fucolipids accumulating in human adenocarcinoma. II. Selective isolation of hybridoma antibodies that differentially recognize mono-, di-, and trifucosylated type 2 chain.
A series of glycolipids having the X determinant (Gal beta 1----4 [Fuc alpha----3]GlcNAc) at the terminus and a fucosyl alpha 1----3 residue at the internal GlcNAc residue have been isolated and characterized from tumor tissues (Hakomori, S., Nudelman, E., Levery, S.B., and Kannagi, R. (1984) J. Biol. Chem. 259, 4672-4680. A series of monoclonal antibodies that differentially recognize glycolipids with mono-, di-, and trifucosylated type 2 chain have been isolated and characterized. The antibody FH4 shows a remarkable preferential reactivity towards di-/or trifucosylated type 2 chain, i.e. it does not react with monofucosylated structures, including lactofucopentaosyl (III) ceramide (III3FucnLc4), monofucosyl neolactonorhexaosylceramide (y2, V3FucnLc6), and monofucosyl neolactonoroctaosylceramide (Z1, VII3FucnLc8), but reacts well with di- and trifucosylated type 2 chain structures such as difucosyl neolactonorhexaosylceramide (III3V3Fuc2nLc6) and trifucosyl neolactonoroctaosylceramide (III3V3VII3Fuc3nLc8). Two other monoclonal antibodies, FH5 and ACFH18, preferentially react with trifucosylated type 2 chain structure (III3V3VII3Fuc3nLc8), although cross-reactivity with difucosylated type 2 chain (III3V3Fuc2nLc6) was observed. They showed a minimal cross-reaction with monofucosylated type 2 chain. In contrast, the antibody FH1 does not react with III3FucnLc4 but reacts with V3FucnLc6, III3V3Fuc2nLc6, and III3V3VII3Fuc3nLc8. Two monoclonal antibodies, FH2 and FH3, do not discriminate among various glycolipids having fucosylated type 2 chain, and their reactivities are essentially similar to previously established antibodies directed to the X determinant, such as anti-SSEA-1, WGHS 29, VEP8 and 9, My-1, etc. This series of antibodies will be useful to detect the specific type of glycolipid with fucosylated type 2 chain accumulating in human cancer and in undifferentiated cells.


Hormonal effects on fatty-acid synthase in cultured fetal rat lung; induction by dexamethasone and inhibition of activity by triiodothyronine.
We previously reported that administration of dexamethasone to the pregnant dam increased the activity of fatty-acid synthase (EC 220.127.116.11) in fetal rat lung and that this effect was reduced when triiodothyronine (T3) was also administered. To determine whether the hormones act directly on the lung, we examined their effects in organ culture. Explants of 18-day and 19-day fetal rat lung were cultured with 100 nM dexamethasone or 100 nM T3, the two hormones together or no hormone at all for 48 h, after which fatty-acid synthase was assayed. Dexamethasone increased fatty-acid synthase activity at both gestational ages. T3 alone had no effect on 18-day, but decreased the activity in 19-day explants by 20%. T3 reduced the stimulatory effect of dexamethasone from 177% to 102% and from 61% to 22% in 18- and 19-day explants, respectively. The effects of dexamethasone and T3 were concentration dependent, with EC50 (concentration achieving 50% of the maximum effect) values of 0.65 nM and approx. 25 nM, respectively. This dexamethasone EC50 is lower than the reported Kd for dexamethasone binding, but the T3 EC50 is considerably higher than its reported Kd. The physiological significance of the T3 effect is, therefore, not clear. The effect of dexamethasone was not apparent until at least 12 h after exposure to the hormone and it was abolished by actinomycin D. Immunoprecipitation with antibody against rat liver fatty-acid synthase showed that there was more fatty-acid synthase in the dexamethasone-treated than in the control cultures. The potency order of glucocorticoids in stimulating fatty-acid synthase was similar to that previously reported for specific nuclear glucocorticoid binding. These data show that dexamethasone and T3 act directly on the fetal lung and that the stimulatory effect of the glucocorticoid on fatty-acid synthase is due to new protein synthesis.


Relevance of CONSORT reporting criteria for research on eHealth interventions.
In 1996, 2001, and 2010, the Consolidated Standards of Reporting Trials (CONSORT) group released criteria for reporting critical information about randomized clinical trials [1,2]. These criteria were intended to improve the quality and completeness of reporting of RCTs in health care research. This paper discusses the relevance of the CONSORT recommendations for the reporting and design of eHealth research. We reviewed the CONSORT recommendations and discussed their particular relevance to eHealth (electronic information, support and/or communication resources designed to promote health) research. This review focuses on such issues as recruitment and screening of participants, description of treatment elements, and reporting of outcome data and adverse events. eHealth research presents special challenges regarding the comprehensive and effective reporting of research information. However, the strategic application of CONSORT recommendations holds great promise for improving the quality and informativeness of eHealth research. Investigators need to consider CONSORT recommendations at all stages of the research enterprise, including planning, execution and reporting in order to increase the informativeness of their research efforts. The recommendations contained in this paper have the potential to enhance the public health and scientific value of eHealth research.


Enhancing the thermoelectric power factor by using invisible dopants.
Nanoparticle dopants that are invisible to conduction electrons and have sharp dips in their electron scattering rate versus electron energy close to the Fermi level. Replacement of such dopants with traditional impurities results in simultaneous enhancement of the Seebeck coefficient and the electron mobility and therefore a large enhancement in the thermoelectric power factor can be achieved.


Non-communicating intramuscular ganglia.
Intramuscular ganglia are rare. Most of the previously reported cases were connected with an adjacent joint. We present the imaging findings in three patients who had intramuscular ganglia that were not connected with a joint. Magnetic resonance showed a septated, encapsulated mass that was isoor hypointense to muscle on T1-weighted and hyperintense on T2-weighted images. A post-contrast T1-weighted scan in one patient showed minimal capsular enhancement. Ultrasound performed in one case showed an encapsulated, anechoic mass.


Factors predicting episodic memory changes in older adults with subjective cognitive decline: A longitudinal observational study.
Episodic memory is affected early in the neuropathological process of Alzheimer's dementia. This study was performed to identify longitudinal associations between baseline vascular/neuropsychiatric risk factors and episodic memory changes over 4.1 ± 2.4 years in 1,401 older adults with subjective cognitive decline (age 74.0 ± 8.2 years). Data were from the National Alzheimer's Coordinating Center-Uniform Data Set and linear mixed effects regression models were used. Reference was those without risk factors. Participants with hypercholesterolemia and with former cigarette smoking had higher episodic memory scores, but current smokers had fewer points than reference at their first and follow-up visits. Despite no difference at baseline, episodic memory scores decreased in those with depressive symptoms relative to reference over time. In older adults with subjective cognitive decline, interventions managing current smoking and depressive symptoms could preserve episodic memory, which may result in delaying the onset of Alzheimer's dementia. Further research is required for the role of cholesterol and smoking.


Increase of insulin sensitivity and reversal of age-dependent glucose intolerance with inhibition of ASIC3.
Glucose tolerance progressively declines with age in humans and is often accompanied by insulin resistance and a high prevalence of type 2 diabetes. Little is known about the mechanism underlying the age-related changes in glucose metabolism. Here we reported that acid-sensing ion channel 3 (ASIC3) is functionally expressed in adipose cells. ASIC3(-/-) mice were protected against age-dependent glucose intolerance with enhanced insulin sensitivity. Acute administration of ASIC3-selective blocker APETx2 improved the glucose control and increased the insulin sensitivity in older (25-27 weeks) ASIC3(+/+) mice. Moreover, the enhanced glucose control in aging ASIC3(-/-) mice was associated with high baseline levels of Akt phosphorylation and high copy number of mitochondrial DNA in adipose tissues. Taken together, our data suggest that ASIC3 signaling might be involved in the control of age-dependent glucose intolerance and insulin resistance.


Detection of angiogenesis activity in malignant bladder tissue and cells.
Neoplastic and non-neoplastic mammalian urothelium was tested for angiogenesis activity in the rabbit iris assay. Tiny fragments of tissue were placed on a rabbit's iris and observed through a slit lamp stereoscope for as long as 4 days after implantation. Angiogenesis activity was demonstrated either by the appearance of new capillary growth or, following an injection of fluorescein, by a green fluorescence around an implant. Capillary proliferation was stimulated by 99 per cent of the specimens containing malignant urothelium, while only 9 per cent of normal urothelial specimens had this effect (p less than .001). Cells grown in vitro were similarly tested for angiogenesis by implanting 1 mm. fragments of collagen coated either with malignant or normal cells. A total of 92 per cent of the specimens covered with neoplastic cells induced angiogenesis, while only 15 per cent of the implants covered by normal cells caused this response (p less than .001). Benign reversible hyperplasia was induced in a rabbit bladder by systemic administration of cyclophosphamide, and an angiogenic response could not be detected in a small number of specimens. The results suggest that angiogenesis activity may be a reliable method for distinguishing between benign and malignant bladder tissue.


Dose-Response Relation Between Work Hours and Cardiovascular Disease Risk: Findings From the Panel Study of Income Dynamics.
The aim of this study was to examine the presence of a dose-response relationship between work hours and incident cardiovascular disease (CVD) in a representative sample of U.S. workers. A retrospective cohort study of 1926 individuals from the Panel Study of Income Dynamics (1986 to 2011) employed for at least 10 years. Restricted cubic spline regression was used to estimate the dose-response relationship of work hours with CVD. A dose-response relationship was observed in which an average workweek of 46 hours or more for at least 10 years was associated with an increased risk of CVD. Compared with working 45 hours per week, working an additional 10 hours per week or more for at least 10 years increased CVD risk by at least 16%. Working more than 45 work hours per week for at least 10 years may be an independent risk factor for CVD.


Pulmonary artery sling with tracheal stenosis: one-stage repair.
Pulmonary artery sling with tracheal stenosis is a difficult management problem. We describe the use of cardiopulmonary bypass as a method to facilitate one-stage repair.


IL-17 receptor-based signaling and implications for disease.
IL-17 is a highly versatile pro-inflammatory cytokine crucial for a variety of processes, including host defense, tissue repair, the pathogenesis of inflammatory disease and the progression of cancer. In contrast to its profound impact in vivo, IL-17 exhibits surprisingly moderate activity in cell-culture models, which presents a major knowledge gap about the molecular mechanisms of IL-17 signaling. Emerging studies are revealing a new dimension of complexity in the IL-17 pathway that may help explain its potent and diverse in vivo functions. Discoveries of new mRNA stabilizers and receptor-directed mRNA metabolism have provided insights into the means by which IL-17 cooperates functionally with other stimuli in driving inflammation, whether beneficial or destructive. The integration of IL-17 with growth-receptor signaling in specific cell types offers new understanding of the mitogenic effect of IL-17 on tissue repair and cancer. This Review summarizes new developments in IL-17 signaling and their pathophysiological implications.


Host defense peptides in skin secretions of Odorrana tiannanensis: Proof for other survival strategy of the frog than merely anti-microbial.
Genus Odorrana, among all amphibians studied, is generally reported to have the most abundant and diversified anti-microbial peptides even from a single individual frog. In our previous work, 46 cDNA sequences encoding precursors of 22 different anti-microbial peptides (AMPs) were characterized from the skin of frog, Odorrana tiannanensis. In this work, we reported the purification of three AMPs from skin secretions of O. tiannanensis. Their amino acid sequences matched well with the sequences deduced from cDNAs and they were designated as Odorranain-C7HSa, Brevinin-1-OT2 and Odorranain-G-OT, respectively. Furthermore, we selected to analyze the four most structurally diversified sequences among the 22 AMPs that are significantly different from all reported AMPs. By structural characterization, three of them were designated as pleurain-E-OT, odorranain-G-OT, odorranain-A-OT, belonging to AMP families already identified. The forth one with a unique 14-mer sequence of AILTTLANWARKFLa and C-terminal amidation represents the prototypes of a new class of amphibian AMP, and thereby named tiannanensin. Such broad diversity in sequences and structures are consistent with other species in Genus Odorrana. Multi-functions of the synthesized four special AMPs were screened, including anti-microbial, antioxidant, cytotoxic and hemolytic activities. The results suggest that these AMPs may employ sophisticated mechanisms of action in host defense in addition to anti-microbial, although their precise contribution to host defense still seems unclear.


In vivo antitumor effect of cromolyn in PEGylated liposomes for pancreatic cancer.
A PEGylated liposomal formulation of cromolyn, composed of dipalmitoylphosphatidylcholine (DPPC), dimyristoylphosphatidylcholine (DMPC), distearoylphosphatidylcholine (DSPC) and 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-mPEG2000), has been developed with the purpose of improving the antitumor activity of cromolyn for human pancreatic adenocarcinoma. In stability study, the amount of proteins adsorbed onto the PEGylated liposomes encapsulating cromolyn was 4.5-fold lower than the non-PEGylated liposome. In vitro study showed that the cromolyn in PEGylated liposome exhibited better anti-proliferative effect in BxPC-3 cells than in Panc-1 cells, which indicates higher level of endogenous S100P protein in BxPC-3 cells than in Panc-1 cells as a target protein for this drug. Moreover, the combination of cromolyn with gemcitabine in PEGylated liposomes demonstrated the strongest cytotoxicity to BxPC-3 pancreatic cancer cells in vitro and the highest anti-tumor activity against the BxPC-3 tumor bearing nude mice in vivo. Thus, this PEGylated liposomal formulation of cromolyn is expected to provide a novel approach to the treatment of pancreatic cancer in the future.


Prognostic features of multiple myeloma.
The outcome of myeloma patients is highly heterogeneous, with survival ranging from a few months to more than 10 years. Accordingly, investigation of prognostic factors may contribute to identification of risk categories and to provision of more accurate information about individual disease outcome. For many years prognostic factors have relied on clinical parameters such as age, hemoglobin level and renal function. Subsequently, biological parameters such as the proliferative activity of plasma cells and beta2-microglobulin have been added to the prognostic arsenal. More recently, cytogenetic and molecular markers with significant influence on disease outcome have been identified. Here we will review the most relevant prognostic factors reported in the literature in patients treated with both conventional chemotherapy and high-dose therapy followed by autologous stem-cell support, as well as in asymptomatic MM and MGUS patients.


Expression of a novel type I keratin, DAPK-1 in the dorsal aorta and pronephric duct of the zebrafish embryos.
We isolated a novel cytokeratin gene of zebrafish (Danio rerio), DAPK-1 closely related to other vertebrate type I cytokeratin genes. Zygotic transcription starts at the sphere stage. After the mid-blastula stage, DAPK-1 is expressed in all surface cells, notably in those of the outer enveloping layer. DAPK-1 messages are also present specifically during the segmentation, pharyngula, and hatching periods. In particular, after 24 h post-fertilization, its expression is restricted to the developing eye region, otic vesicle, pectoral fin, dorsal aorta, and pronephric duct. In the mindbomb mutant embryo that has defects in the dorsal aorta development, DAPK-1 transcripts are not detected in the dorsal aorta and pronephric duct. The characteristic expression pattern of DAPK-1 may facilitate more detailed studies related to the morphogenesis of dorsal aorta and pronephric duct.


[Physico-chemical and immunochemical characteristics of oncoprecipitins of crustacin and cyprein specifically reacting with carcinoembryonic antigen].
Crustacin from Pagurus prideauxii and cyprein from Cyprea caputserpentis have been shown to be glycoproteins with molecular masses 36 +/- 1 and 44 +/- 1.4 kDa, containing 3 and 18% of carbohydrates, respectively. Their amino acid and monosaccharide composition have been determined. Crustacin or cyprein interact with CEA more specifically than carbohydrate-containing polymers with lectins. Carbohydrates unspecifically inhibit this interaction at rather high concentrations. Association constants of CEA-crustacin and CEA-cyprein complexes are 0.6.10(8) M-1, respectively. Besides, ELISA showed that antibodies against CEA bind antibodies to crustacin and cyprein.


IGF-I and IGFBP-3 before and after inpatient alcohol detoxification in alcohol-dependent subjects.
It is unclear whether alcohol detoxification has an effect on factors that are involved in growth, metabolic functions and cell proliferation. Alcohol abuse is associated with low IGF-I levels that tend to rise after alcohol withdrawal. There is a paucity of studies on the course of IGFBP-3 (the main binding protein for IGF-I) after alcohol detoxification. We prospectively assessed IGF-I and IGFBP-3 changes at the time of admission and after 4 to 6 weeks of detoxification in an inpatient alcohol detoxification facility in 118 alcohol-dependent subjects given a regular hospital diet. No participants dropped out of the study. Changes in IGF-I after alcohol detoxification showed a marked dimorphism in altered hepatic biochemistry upon admission, with a rise in those with normal liver enzymes upon admission (p = 0.016, Kruskall-Wallis) and a drop in those with elevated liver enzymes upon admission (p = 0.05); the latter was noted in subjects that had consumed alcohol close to the time of admission. Overall, however, IGF-I and IGFBP-3 were within normal limits for most subjects both upon admission and after alcohol detoxification; no significant differences were detected among the examined parameters in men vs. women, and there were no significant correlations of IGF-I, IGFBP-3 or the IGF-I/IGFBP-3 molar ratio with BMI or age. Regardless of hepatic enzymes' elevation, alcohol detoxification had overall slight effects on IGF-I and IGFBP-3.


Analgesic effects and arthritic changes following intra-articular injection of diclofenac etalhyaluronate in a rat knee osteoarthritis model.
Diclofenac etalhyaluronate (DF-HA) is a recently developed analgesic conjugate of diclofenac and hyaluronic acid that has analgesic and anti-inflammatory effects on acute arthritis. In this study, we investigated its analgesic effect on osteoarthritis, using a rat model of monoiodoacetate (MIA). We injected MIA into the right knees of eight 6-weeks-old male Sprague-Dawley rats. Four weeks later, rats were randomly injected with DF-HA or vehicle into the right knee. Seven weeks after the MIA injection, fluorogold (FG) and sterile saline were injected into the right knees of all the rats. We assessed hyperalgesia with weekly von Frey tests for 8 weeks after MIA administration. We took the right knee computed tomography (CT) as radiographical evaluation every 2 weeks. All rats were sacrificed 8 weeks after administration of MIA for histological evaluation of the right knee and immunohistochemical evaluation of the DRG and spinal cord. We also evaluated the number of FG-labeled calcitonin gene-related peptide (CGRP)-immunoreactive(ir) neurons in the dorsal root ganglion (DRG) and ionized calcium-binding adapter molecule 1 (Iba1)-ir microglia in the spinal cord. Administration of DF-HA significantly improved pain sensitivity and reduced CGRP and Iba1 expression in the DRG and spinal cord, respectively. However, computed tomography and histological evaluation of the right knee showed similar levels of joint deformity, despite DF-HA administration. DF-HA exerted analgesic effects on osteoarthritic pain, but did not affect joint deformity.


Parasite contamination of soil in households of a Mexican rural community endemic for neurocysticercosis.
High neurocysticercosis (NC) prevalence was recently determined by a computed tomography (CT) scan study in the community of Tepetzitzintla, State of Puebla, Mexico. The aim of the present work was to evaluate the magnitude of fecal and parasite contamination by Taenia spp. in the soil of households of this community during the four seasons of the year. The toilet, backyard, kitchen, washboard, water containers and corrals of 14 to 26 households were sampled during each season. High Taenia spp. egg intensity was found in 24.2% of the sampled areas. The highest percentage was detected in Spring and the lowest in Summer. Significantly higher levels of Taenia spp. eggs were present in kitchen soil samples. A significant correlation was found between the presence of Taenia spp. eggs in household soil during the Summer, and NC diagnoses of the inhabitants by CT scan. Coproparasitological examinations and anti-cysticercal antibodies were determined in a cohort of inhabitants of the sampled households. Antibody levels and coproparasitological results were not associated with NC. Overall, these results illustrate the high degree of fecal contamination of potential risk to human health in rural communities and could be of use for control programmes.


Maternal Mortality and Morbidity by Cause in Provinces of Iran, 1990 to 2019: An Analysis for the Global Burden of Disease Study 2019.
Since 1990, maternal mortality ratio (MMR) has significantly decreased in Iran. However, estimates for mortality and morbidity by cause at subnational scale are not available. This study is part of the Global Burden of Diseases study (GBD) 2019. Here we report maternal mortality and morbidity by age and cause across 31 provinces of Iran from 1990 to 2019. Since 1990, MMR declined from 44.5 (95% UI: 38.6-50.1) to 15.9 (14.7-17.3) per 100000 live births in Iran. In 1990 MMR ranged from 18.5 (11.2-26.4) to 76.9 (38.4-114.7) per 100000 live births across provinces. Respective figures for 2019 were 7.1 (5.2-9.3) to 34.0 (25.1-44.7) per 100000 live births. In 2019, MMR was higher in young women (aged 10 to 14) and older women (aged 45 or more). Percentages of deaths under 25 years was 24.8% in 1990 and 16.0% in 2019. There was remarkable decline in years lost due to premature death (YLL) rates from 1990 to 2019. While the decline was modest for years lived with disability (YLD) rates. Indirect maternal deaths and other maternal deaths ranked first or second in almost all provinces. Ultimately, there was an evident decrease in MMR along with increase in socio-demographic Index (SDI) from 1990 to 2019 in all provinces and an evident convergence across provinces. MMR has declined to levels much lower than Sustainable Development Goals in all provinces. Although there was a convergence in trends, there are still disparities across provinces. The decline in disabilities caused by maternal disorders is not as significant as mortality, which needs further actions.


Guideline-based early rehabilitation after myocardial infarction. A pragmatic randomised controlled trial.
To determine the effectiveness of individualised educational behavioural treatment delivered by cardiac nurses in hospital compared to usual care for patients following acute myocardial infarction. One hundred and fourteen consecutive patients were randomised to receive the intervention or usual care. Outcome assessment was by self-report questionnaire (the Hospital Anxiety and Depression Scale and Dartmouth COOP Health Status), interview at 1 month, and self-report at 3 and 12 months. The primary outcome was improvement in the Dartmouth COOP total score from baseline to 3 months. Four patients needed to be treated to give an additional patient with improvement in health status at 3 months (number needed to treat [NNT] 4, 95% confidence intervals [CIs] 3 to 12). The intervention group were more confident about returning to activities 1 month after discharge from hospital. Treated patients had fewer further treatment needs. An individualised educational behavioural treatment delivered by cardiac nurses in hospital may have substantial benefits. A large-scale pragmatic RCT is needed.


Advances in vaccinia virus-based vaccine vectors, with applications in flavivirus vaccine development.
Historically, virulent variola virus infection caused hundreds of millions of deaths. The smallpox pandemic in human beings has spread for centuries until the advent of the attenuated vaccinia virus (VV) vaccine, which played a crucial role in eradicating the deadly contagious disease. Decades of exploration and utilization have validated the attenuated VV as a promising vaccine vehicle against various lethal viruses. In this review, we focus on the advances in VV-based vaccine vector studies, including construction approaches of recombinant VV, the impact of VV-specific pre-existing immunity on subsequent VV-based vaccines, and antigen-specific immune responses. More specifically, the recombinant VV-based flaviviruses are intensively discussed. Based on the publication data, this review aims to provide valuable insights and guidance for future VV-based vaccine development.


Advances in the Treatment of Neuromyelitis Optica Spectrum Disorder.
Neuromyelitis optica spectrum disorder (NMOSD) is a rare, relapsing-remitting neuroinflammatory disorder of the central nervous system. Advances in the understanding of NMOSD pathogenesis and identification of the NMO-specific pathogenic anti-AQP4 autoantibody have led to the development of highly effective disease-modifying strategies. Five placebo-controlled, randomized trials for NMOSD have been successfully completed as of 2020. These trials support the efficacy of rituximab and tocilizumab and led to the FDA approval of eculizumab, satralizumab and inebilizumab for NMOSD. Our review provides an update on these evidence-based disease-modifying therapies and discussed the treatment of acute relapses in NMOSD.


Distinct domains of small Tims involved in subunit interaction and substrate recognition.
Tim9 and Tim10 belong to the small Tim family of mitochondrial ATP-independent chaperones. They are organised in a specific hetero-oligomeric complex (TIM10) that escorts polytopic proteins into the mitochondrial inner membrane. The contributions of the individual subunits to the assembly and function of the TIM10 complex remain poorly understood. Here, we show that substrate recognition and assembly of the complex are mediated by distinct domains of the subunits. These are unrelated to the characteristic "twin CX3C" motif that is present in all small Tims and ensures proper folding of the unassembled subunits. Specifically, we show that substrate recognition is achieved by the Tim10 subunit, whilst Tim9 serves a more structural role. The N-terminal domain of Tim10 is a substrate sensor whilst its C-terminal part is essential for complex formation. By contrast, both N and C-terminal domains of Tim9 are involved in the stability of the complex.


Optimized temperature and deadspace correction improve analysis of multiple breath washout measurements by ultrasonic flowmeter in infants.
Assessment of lung volume (FRC) and ventilation inhomogeneities with ultrasonic flowmeter and multiple breath washout (MBW) has been used to provide important information about lung disease in infants. Sub-optimal adjustment of the mainstream molar mass (MM) signal for temperature and external deadspace may lead to analysis errors in infants with critically small tidal volume changes during breathing. We measured expiratory temperature in human infants at 5 weeks of age and examined the influence of temperature and deadspace changes on FRC results with computer simulation modeling. A new analysis method with optimized temperature and deadspace settings was then derived, tested for robustness to analysis errors and compared with the previously used analysis methods. Temperature in the facemask was higher and variations of deadspace volumes larger than previously assumed. Both showed considerable impact upon FRC and LCI results with high variability when obtained with the previously used analysis model. Using the measured temperature we optimized model parameters and tested a newly derived analysis method, which was found to be more robust to variations in deadspace. Comparison between both analysis methods showed systematic differences and a wide scatter. Corrected deadspace and more realistic temperature assumptions improved the stability of the analysis of MM measurements obtained by ultrasonic flowmeter in infants. This new analysis method using the only currently available commercial ultrasonic flowmeter in infants may help to improve stability of the analysis and further facilitate assessment of lung volume and ventilation inhomogeneities in infants.


Pancreatic metastasis of tall cell variant of papillary thyroid carcinoma: diagnosis by endoscopic ultrasound-guided fine needle aspiration.
The incidence of tall cell variant of papillary thyroid carcinoma that has metastasized to the pancreas is extremely rare. There has been only one previously reported case of pancreatic metastasis of the tall cell variant of papillary thyroid carcinoma. We present the case of a patient who presented with tall cell variant of papillary thyroid carcinoma with metastasis to the pancreas detected and confirmed cytologically by EUS-FNA after finding of the CT scan were equivocal. EUS-FNA is a powerful new tool that can be used for the detection and diagnosis of primary and metastatic lesions of the pancreas.


Intraventricular infusions of antibodies to amyloid-beta-protein precursor impair the acquisition of a passive avoidance response in the rat.
Intraventricular infusions of an antiserum raised against a 14 amino acid residue in the extracellular domain of amyloid-beta-protein precursor significantly decreased stepdown latency, at both 24 h and 48 h recall times, in rats trained to avoid an electroshock by remaining on a platform. The antiserum was effective when infused up to 2.5 h following training and no retention deficit was noted when it was administered at 4h or 6h after training. An antiserum generated against a 17 amino acid residue of the A4 amyloid peptide had no effect on learning. Thus the amyloid precursor protein, which is aberrantly processed in Alzheimer's disease, appears to be directly involved in memory formation.


Prediction of atomic structure from sequence for double helical DNA oligomers.
DNA can adopt different conformations depending on the base sequence, solvent, electrolyte composition and concentration, pH, temperature, and interaction with proteins. Here we present a model for calculating the three-dimensional atomic structure of double-stranded DNA oligomers. A theoretical energy function is used for calculating the interactions within the base steps and an empirical backbone function is used to restrict the conformational space accessible to the bases and to account for the conformational coupling of neighboring steps in a sequence. Conformational searching on large structures or a large number of structures is possible, because each base step can be described by just two primary degrees of freedom (slide and shift). A genetic algorithm is used to search for low-energy structures in slide-shift space, and this allows very rapid optimization of DNA oligomers. The other base step parameters have been previously optimized for all possible slide-shift sequence combinations, and a heuristic algorithm is used to add the atomic details of the backbone conformation in the final step of the calculation. The structures obtained by this method are very similar to the corresponding X-ray crystal structures observed experimentally. The average RMSD is 2.24 Angstroms for a set of 20 oligomer structures. For 15 of these sequences, the X-ray crystal structure is the global energy minimum. The other 5 are bistable sequences that have B-form global energy minima but crystallize as A-DNA.


Isolation of three strains of beta-lactamase-producing Enterococcus faecalis in Argentina.
Of the 90 strains of Enterococcus spp. isolated in an Argentine laboratory in the period from January to July 1989, three were identified as beta-lactamase-producing Enterococcus faecalis. According to the literature reviewed, these appear to be the first beta-lactamase-positive strains of Enterococcus isolated outside the USA. They differed from most beta-lactamase-producing strains already described in that they were susceptible to low concentrations of macrolides. All three strains were resistant to high concentrations of aminoglycosides.


A fluorescence and NMR relaxation study of thermally-induced conformational changes in liver alcohol dehydrogenase.
Fluorescence and NMR relaxation studies have been performed on horse liver alcohol dehydrogenase (alcohol: NAD + oxidoreductase, EC 220.127.116.11) as a function of temperature. Observations of both the intrinsic protein fluorescence and the fluorescence of a noncovalently bound apolar probe, 2-(p-toluidinyl)naphthalene-6-sulfonic acid (TNS), indicate that a significant thermal transition occurs in the protein in the range of temperature 0-40 degrees C, and that there are different temperature-dependent forms of the enzyme. The transition between these forms is affected by the binding of specific ligands to the enzyme's active site. Time-resolved fluorescence studies of the two tryptophan residues in the enzyme suggest that this thermal transition occurs around tryptophan-314, which is buried near the intersubunit region. Binding of nucleotide to the enzyme causes a decrease in spin-lattice relaxation time, T1, which may result from a decrease in the number of water molecules bound to the protein. The observed results may be due to the interactions between the structural domains into which the monomer of the protein is folded.


Psychophysical observations on patients with neuropathic pain relieved by a sympathetic block.
Patients with sympathetically maintained pain (SMP) were tested with noxious heat pulses, innocuous mechanical stimuli, and transcutaneous electrical nerve stimulation before and during local anesthetic sympathetic blocks that relieved their pain. The perceived intensity of the pain evoked by these stimuli was measured by the patients' responses on a visual analog scale and compared to the responses obtained when the same stimuli were applied to contralateral normal skin. In 5 of 7 patients tested, graded noxious heat stimuli (43-51 degrees C) applied to painful skin resulted in heat-pain intensity ratings that were essentially identical to the responses obtained when the same stimuli were applied to the normal side. Of the remaining two patients, one was clearly hypoalgesic for heat-pain and the other was probably hyperalgesic. The normal and subnormal heat-evoked responses obtained from abnormal skin were unchanged during completely successful sympathetic blocks. Trains of noxious heat pulses (52 degrees C) evoked summation of the second pain sensation in each of the 4 patients tested. This summation effect was normal and unaffected by a sympathetic block. Four of the patients had allodynia evoked by mechanical stimulation. In each of the 3 allodynia cases tested, transcutaneous nerve stimulation at an intensity that was at threshold for detection evoked burning pain and a coexistent sensation of tingle, indicating that both sensations were due to the activation of A beta axons. Patients without touch-evoked pain reported that electrical stimuli at threshold for detection produced only the sensation of tingle. The pains evoked by touch and by threshold-strength nerve stimulation were eliminated during sympathetic block. In patients with allodynia, trains of gentle mechanical stimuli and trains of threshold-strength electrical nerve stimuli produced summation of the intensity of the burning pain sensation when the stimuli were presented at 0.3 Hz. These results add to a growing body of evidence indicating that the touch-evoked pain of some patients is due to abnormal central activity evoked by input from A beta low-threshold mechanoreceptors. The coexistence of A beta-evoked pain with normal heat-evoked pain and normal heat-pain summation suggests that the central abnormality cannot be a simple hypersensitivity of wide-dynamic-range neurons. The effect of sympathetic blockade on A beta-evoked pain and its summation suggests that the crucial sympathetic interaction may take place centrally. The results show that there is considerable heterogeneity of sensory abnormalities among patients with SMP.(ABSTRACT TRUNCATED AT 400 WORDS)


Proposal of a new formula to calculate total urinary nitrogen from urea urinary nitrogen.
Urea urinary nitrogen (UUN) and total urinary nitrogen (TUN) were determined in 15 patients to study their relationship mainly in highly catabolic patients. The subjects were: 7 multiple trauma, 3 autologous bone-marrow transplant, 1 tetanus, 4 postcholecystectomy patients; 180 determination were made, 111 of which in highly catabolic phase (TUN > 15 g/day). TUN and UUN are well correlated (r = 0.9742; p < 0.001) in the range 3 to 52 g/ day of TUN. Urea represents the 83.2 +/- 9.4% (M +/- SD). A double-linear formula to calculate TUN from UUN is proposed (for UUN 15 g/ day: TUN = UUN x 1.17 + 0.7; for UUN > 15 g/ day: TUN = UUN + 4). The least square procedure was used to compare the differences between measured and calculated TUN, and the results obtained with the proposed double-linear formula were compared with that obtained employing pre-existing formulas (Lee's and Mackenzie's). Considering all ranges of values studied (3-52 g of TUN) the results obtained were significantly different (p < 0.005); dividing the levels of TUN in 15 g; 16-29 g and 30 g, the results were always better, but the statistical significancy was not always reached.


Insights on pretreatment technologies for partial nitrification/anammox processes: A critical review and future perspectives.
For almost 20 years, partial nitrification-anammox (PN/A) has been the subject of intensive study and development. Pretreatment of wastewater for PN/A is crucial because the inhibitory substances in the influent may reduce the performance of PN/A. In this review, the current PN/A pretreatment technologies are comprehensively summarized. The selection of pretreatment technology for PN/A depending on the source of the wastewater and its main characteristics (high-strength wastewater or municipal wastewater, organic matters, suspended solids). Comparison of pretreatment technologies through multiple perspectives including wastewater characteristics, the objectives of the wastewater treatment (treating requirement, energy and resource recovery demand), reactor configuration of PN/A. Based on the discussion, two integrated processes, HRAS + one-stage PN/A and advanced AD + two-stage PN/A, are recommended as the preferred processes for treating municipal wastewater and wastewater with a high-strength ammonium, respectively. This review aims to provide guidance for future research and development of PN/A.


Does thenumber of stepsneededfor UCM gait analysisdiffers between healthy and stroke?
The basis for the uncontrolled manifold (UCM) approach is the variability among repetitions of a motor task. Thus, reliable results might be influenced by the number of trials. This study estimated the number of steps needed for UCM analysis of stroke gait and if it is the same for healthy subjects. Twenty-five volunteers participated, sixteen in the stroke group (age 59.0 ± 7.5 years, ten hemiparesis at right), and nine in the healthy group (age 59.2 ± 4.9 years). We applied the UCM analysis over each lower limb's single support phase (SSP). The center of mass in the sagittal plane was the task variable, and the ankle, knee and hip joint angles, the elemental variables. The results obtained with 40 steps were used as a reference and compared with those obtained separately from 10, 20, and 30 steps. The mean values of the curves along the SSP were compared between the sets of steps. Further, for each volunteer, we calculated the Pearson correlation between the 40 steps curve and those obtained with other numbers of steps. Our results indicate that (1) the number of steps necessary to perform UCM analysis of stroke gait is larger than those necessary in healthy condition, (2) the synergy index is less sensitive to the number of steps than the UCM components (V_UCM and V_ORT), and (3) the analysis of the UCM over time requires a more significant number of steps than the mean values.


Application of X-ray fluorescence for the analysis of some technological materials.
Various X-ray fluorescence techniques have been developed for the determination of the composition of two- and three-component alloys. It has been found experimentally and confirmed theoretically that in some alloys, the composition can be determined without taking into account the absorption and secondary excitation of analytical characteristic lines, indicating that the contributions of these effects are opposite. X-ray techniques have also been applied to determine the composition of various kinds of technological waste. As a rule, waste contains many so-called "light" elements (Z < 19) for which characteristic lines cannot be detected. In these cases, an independent measurement of the quantity of one of these elements is necessary to determine the quantities of the others. In most of the cases, instrumental neutron activation analysis is used for the independent measurement.


Management of symptomatic fibroids: conservative surgical treatment modalities other than abdominal or laparoscopic myomectomy.
Approximately 50% of women of reproductive age have fibroids, and at least 50% of these women have significant symptoms. However, until 15 years ago, the only surgical options available were hysterectomy and myomectomy, and as yet there are no proven effective long-term medical therapies. Fortunately, the past decade has witnessed the emergence of highly sophisticated diagnostic and therapeutic technologies for fibroids. Magnetic resonance imaging and high-resolution ultrasound are non-invasive, high-quality diagnostic procedures. The new treatment modalities include: laparoscopic and vaginal myomectomy; uterine artery embolization (UAE); magnetic-resonance-guided focused ultrasound surgery (MRgFUS); hysteroscopic resection where the fibroids are submucous; myolysis by heat, cold coagulation and laser; laparoscopic uterine artery occlusion; and temporary transvaginal uterine artery occlusion. It is, however, abundantly clear that there is no panacea that suits every woman, nor are all treatment types universally available to all women, even in the developed world. Laparoscopic surgery requires skills that are not common place, and there are limitations on the size and number of fibroids that can be treated by this modality. Much the same applies to vaginal myomectomy. UAE is now widely used in the USA and Western Europe, and has been recommended by the National Institute for Clincial Excellence (NICE) in the UK as an alternative therapy to hysterectomy. However, UAE is still under evaluation in terms of comparison with myomectomy. UAE has a range of complications including premature ovarian failure, chronic vaginal discharge and pelvic sepsis, and may have limited efficacy when the fibroids are large. Although there are a number of reports of successful pregnancy following UAE, the experience is limited and research is required in this area. MRgFUS was approved by the US Food and Drug Administration in 2004, while NICE recommended that the procedure should be used in an audit and research setting. Preliminary data following laparoscopic uterine artery occlusion suggest that outcomes are similar to those with UAE, but these data are derived from studies involving relatively small numbers. Temporary uterine artery occlusion is also promising, but has yet to be evaluated robustly. Thus there is no room for complacency; research involving the available treatment modalities is urgently needed, while innovations in search of newer and more effective therapies must continue. This chapter will review surgical treatment modalities other than hysterectomy and abdominal or laparoscopic myomectomy.


[Effectiveness of an educational program for respiratory rehabilitation of Chronic Obstructive Pulmonary Disease patients in Primary Care in improving the quality of life, symptoms, and clinical risk].
To determine the impact of an educational program to improve the management of chronic obstructive pulmonary disease (COPD) that contributes to an increase of the quality of life, exercise capacity, level of dyspnoea, and clinical risk. Intervention study without controls. Primary Healthcare Centre. 193 patients with COPD were invited, 73 accepted and 55 participated in the educational program. Respiratory rehabilitation educational program with basic concepts of pulmonary and respiratory pathophysiology, respiratory physiotherapy exercises, practical workshop on the use of the most frequent inhalation devices, understanding of chronic disease and self-care measures in case of exacerbation. The quality of life (the COPD assessment test), exercise tolerance (the Six-Minute Walk Test), rating of perceived exertion (Borg Dyspnoea Score) and clinical risk (BODE index) were assessed by means of validated questionnaires in Spanish. A total of 43 (78.2%) participants completed the program. An improvement in the quality of life by a mean of 3.3 points was observed (95%CI; 1.76-4.84). Just over half (53.5%) of the participants obtained a clinically relevant improvement. Participants also improved their physical exercise capacity at post-intervention by increasing the distance that they walked in 6min by a mean of 20.76m (95%CI; 2.57-38.95). Improvements in the level of dyspnoea and clinical risk were also observed. The educational program shows a statistically significant and clinically relevant improvement in the quality of life, fatigue, symptomatology, exercise capacity, level of dyspnoea, and clinical risk. The program is adaptable to the health care routine of healthcare centres.


A novel metabolic subtype with S100A7 high expression represents poor prognosis and immuno-suppressive tumor microenvironment in bladder cancer.
Bladder cancer (BLCA) represents a highly heterogeneous disease characterized by distinct histological, molecular, and clinical features, whose tumorigenesis and progression require aberrant metabolic reprogramming of tumor cells. However, current studies have not expounded systematically and comprehensively on the metabolic heterogeneity of BLCA. The UCSC XENA portal was searched to obtain the expression profiles and clinical annotations of BLCA patients in the TCGA cohort. A total of 1,640 metabolic-related genes were downloaded from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Then, consensus clustering was performed to divide the BLCA patients into two metabolic subtypes according to the expression of metabolic-related genes. Kaplan-Meier analysis was used to measure the prognostic values of the metabolic subtypes. Subsequently, comparing the immune-related characteristics between the two metabolic subtypes to describe the immunological difference. Then, the Scissor algorithm was applied to link the metabolic phenotypes and single-cell transcriptome datasets to determine the biomarkers associated with metabolic subtypes and prognosis. Finally, the clinical cohort included 63 BLCA and 16 para-cancerous samples was used to validate the prognostic value and immunological correlation of the biomarker. BLCA patients were classified into two heterogeneous metabolic-related subtypes (MRSs) with distinct features: MRS1, the subtype with no active metabolic characteristics but an immune infiltration microenvironment; and MRS2, the lipogenic subtype with upregulated lipid metabolism. These two subtypes had distinct prognoses, molecular subtypes distributions, and activations of therapy-related pathways. MRS1 BLCAs preferred to be immuno-suppressive and up-regulated immune checkpoints expression, suggesting the well-therapeutic response of MRS1 patients to immunotherapy. Based on the Scissor algorithm, we found that S100A7 both specifically up-regulated in the MRS1 phenotype and MRS1-tumor cells, and positively correlated with immunological characteristics. In addition, in the clinical cohort included 63 BLCA and 16 para-cancerous samples, S100A7 was obviously associated with poor prognosis and enhanced PD-L1 expression. The metabolic subtype with S100A7 high expression recognizes the immuno-suppressive tumor microenvironment and predicts well therapeutic response of immunotherapy in BLCA. The study provides new insights into the prognostic and therapeutic value of metabolic heterogeneity in BLCA.


Spontaneous innominate and left common carotid artery dissection with bovine aortic arch.
We describe a case of a 63-year-old woman who presented with spontaneous dissection of the innominate and left common carotid arteries arising from a common trunk, so-called "bovine aortic arch." The entry tear was seen in the common trunk at the origin of the innominate artery with no dissection extending into the aortic arch or the ascending aorta. The dissection was resected and total arch replacement was performed considering the aortic wall fragility complicated by the dissection.


Gluten measurement and its relationship to food toxicity for celiac disease patients.
The gluten analysis of foods has long had limitations, which have precluded food standards authorities from issuing standards for gluten-free foods based on final gluten content. The Codex Alimentarius and the Food and Drug Administration have taken steps towards such standards in which they favour the R5-enzyme-linked immunosorbent assay for gluten analysis. If this method is to be widely employed, its limitations should be recognised. Above all, it should be noted the ability of R5-enzyme-linked immunosorbent assay, and other methods, to measure gluten's toxicity toward celiac disease patients is not validated clinically. Gluten is a complex mixture of proteins and its toxicity is not fully understood. Analytical methods are a valuable tool in the definition of gluten-free foods, but they should be employed with appropriate caveats in ensuring the safety of the foods.


Stress-induced responses and open-field behavior in estrous and nonestrous mice.
Three experiments were performed to compare the reactions of estrous and nonestrous female CD-1 mice to stressful stimuli. These experiments revealed no effect of estrous state on (a) response latencies to thermal pain in the mouse hot-place test, (b) immediate, active responses to electric foot shock, or (c) open field ambulation under no stress condition or under stress conditions provided by foot shock or bright light. Estrous mice were found to defecate less in a small open field, and to ambulate more in the center of a large open field, than nonestrous mice, but neither of these effects interacted with an effect of stress condition. An incidental finding was a diurnal effect on response latencies in the mouse hot-place test. These experiments, combined with previous experiments with female CD-1 mice, support the conclusion that estrus results in decreased avoidance of potentially dangerous or stressful places, but does not affect the animal's reactivity to unavoidable stressful stimuli.


Computer-assisted conformation radiotherapy with a variable thickness multi-leaf filter.
A new computer-assisted conformation radiotherapy with a variable thickness multi-leaf filter system was developed. Each wedgeshaped compensating filter (aluminum, tan theta = 0.1) travels against the movement of the ipsilateral leaf and according to defined parameters. By using our filter, a homogenous dose distribution in the target area was obtained and high-dose levels outside the target area decreased significantly.


Conformations, dynamics and interactions of di-, tri- and pentamannoside with mannose binding lectin: a molecular dynamics study.
The binding of serum mannose-binding protein A (MBP-A) to high mannose N-linked glycoproteins, present on the surface of microorganism, activates the complement system. It is very important to explore the overall conformations of these ligands in the binding site of the MBP-A, which is very much dependent on the conformation of the manno-di-, tri- and the penta-saccharides that represent the component structures of these high-mannose type oligosaccharides. Herein, we report the possible conformations of α-(1→6)-linked dimannoside, benzyl-substituted trimannoside and core pentamannoside of the N-linked glycan in the binding site of MBP-A, with the help of molecular dynamics simulations. The results indicate that for all three ligands in addition to the non-reducing terminal mannose moiety the reducing moieties also interact with protein. Binding free energy calculations also indicate that the benzyl-substituted trisaccharide has higher affinity in comparison to the methyl substituted one. We have also found some conformers of the pentasaccharide, which have higher binding affinity than the monosaccharide.


Bioaccessibility of bioactive compounds and antioxidant potential of juçara fruits (Euterpe edulis Martius) subjected to in vitro gastrointestinal digestion.
An in vitro method involving simulated gastrointestinal digestion was used to assess the bioaccessibility of fifteen minerals, twenty-two phenolic compounds and the antioxidant capacity in juçara fruit during seven ripening stages. For minerals and phenolics, respectively, initial contents were up to 1325.9 and 22.9mg100g-1, whereas after in vitro digestion, the maximum values were 556.7 and 14.43mg100g-1 (dry matter). Antioxidant capacity, determined by 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity (DPPH) and ferric reducing antioxidant power (FRAP), after in vitro digestion decreased 51-78% when compared to the crude extract. Bioaccessible fractions of quercetin, protocatechuic and p-coumaric acids presented positive and significant correlation with results of DPPH and FRAP. Furthermore, our study demonstrated that the ripening stages of juçara fruit influenced the bioaccessibility of compounds and antioxidant capacity, which presented higher levels in purple fruits collected 42-69days after the appearance of the red berries on bunches.


Sulfur-based mixotrophic denitrification corresponding to different electron donors and microbial profiling in anoxic fluidized-bed membrane bioreactors.
Sulfur-based mixotrophic denitrifying anoxic fluidized bed membrane bioreactors (AnFB-MBR) were developed for the treatment of nitrate-contaminated groundwater with minimized sulfate production. The nitrate removal rates obtained in the methanol- and ethanol-fed mixotrophic denitrifying AnFB-MBRs reached 1.44-3.84 g NO3 -N/L reactor d at a hydraulic retention time of 0.5 h, which were significantly superior to those reported in packed bed reactors. Compared to methanol, ethanol was found to be a more effective external carbon source for sulfur-based mixotrophic denitrification due to lower sulfate and total organic carbon concentrations in the effluent. Using pyrosequencing, the phylotypes of primary microbial groups in the reactor, including sulfur-oxidizing autotrophic denitrifiers, methanol- or ethanol-supported heterotrophic denitrifiers, were investigated in response to changes in electron donors. Principal component and heatmap analyses indicated that selection of electron donating substrates largely determined the microbial community structure. The abundance of Thiobacillus decreased from 45.1% in the sulfur-oxidizing autotrophic denitrifying reactor to 12.0% and 14.2% in sulfur-based methanol- and ethanol-fed mixotrophic denitrifying bioreactors, respectively. Heterotrophic Methyloversatilis and Thauera bacteria became more dominant in the mixotrophic denitrifying bioreactors, which were possibly responsible for the observed methanol- and ethanol-associated denitrification.


In vivo deuteration strategies for neutron scattering analysis of bacterial polyhydroxyoctanoate.
The cultivation of microorganisms on deuterated substrates has allowed us to control deuterium incorporation into biopolymer systems which is important for characterisation using neutron scattering techniques. Bacterial polyhydroxyoctanoate (PHO) is a polyester formed within inclusions inside bacterial cells and was deuterated in vivo under various conditions to characterise the formation of these inclusions by neutron scattering. Manipulation of deuterated media during microbial growth and PHO production phases resulted in polymer with partial or complete substitution of hydrogen by deuterium, as shown by gas chromatography. Sequential feeding of hydrogenated and deuterated forms of the same precursor was used to demonstrate that neutron scattering analysis could be used to differentiate between chemically similar phases in these polymer inclusions.


Growth Differentiation Factor 15 is a potential biomarker of therapeutic response for TK2 deficient myopathy.
GDF-15 is a biomarker for mitochondrial diseases. We investigated the application of GDF-15 as biomarker of disease severity and response to deoxynucleoside treatment in patients with thymidine kinase 2 (TK2) deficiency and compared it to FGF-21. GDF-15 and FGF-21 were measured in serum from 24 patients with TK2 deficiency treated 1-49 months with oral deoxynucleosides. Patients were grouped according to age at treatment and biomarkers were analyzed at baseline and various time points after treatment initiation. GDF-15 was elevated on average 30-fold in children and 6-fold in adults before the start of treatment. There was a significant correlation between basal GDF-15 and severity based on pretreatment distance walked (6MWT) and weight (BMI). During treatment, GDF-15 significantly declined, and the decrease was accompanied by relevant clinical improvements. The decline was greater in the paediatric group, which included the most severe patients and showed the greatest clinical benefit, than in the adult patients. The decline of FGF-21 was less prominent and consistent. GDF-15 is a potential biomarker of severity and of therapeutic response for patients with TK2 deficiency. In addition, we show evidence of clinical benefit of deoxynucleoside treatment, especially when treatment is initiated at an early age.


Insights into recognition of the T-DNA border repeats as termination sites for T-strand synthesis by Agrobacterium tumefaciens.
The recognition of the T-DNA left border (LB) repeat is affected by its surrounding sequences. Here, the LB regions were further characterized by molecular analysis of transgenic plants, obtained after Agrobacterium tumefaciens-mediated transformation with T-DNA vectors that had been modified in this LB region. At least the 24-bp LB repeat by itself was insufficient to terminate the T-strand synthesis. Addition of the natural inner and/or outer border regions to at least the LB repeat, even when present at a distance, enhanced the correct recognition of the LB repeat, reducing the number of plants containing vector backbone sequences. In tandem occurrence of both the octopine and nopaline LB regions with their repeats terminated the T-strand synthesis most efficiently at the LB, yielding a reproducibly high number of plants containing only the T-DNA. Furthermore, T-strand synthesis did not terminate efficiently at the right border (RB) repeat, which might indicate that signals in the outer RB region inhibit the termination of T-strand synthesis at the RB repeat.


Maleimide-grafted cellulose nanocrystals as cross-linkers for bionanocomposite hydrogels.
This article deals with the preparation of bionanocomposite hydrogels from natural polymers and nanoentities, an emerging class of materials for biotechnological and biomedical applications. Herein, the applicability of the Diels-Alder "click" reaction to the design of bionanocomposite hydrogels from furan modified gelatin using maleimide-functionalized cellulose nanocrystals as multifunctional cocross-linkers is demonstrated. The functionalization of cellulose nanocrystals with maleimide moieties was confirmed by XPS. The swelling and rheological properties of the resulting bionanocomposite confirmed the formation of hydrogel networks with covalently embedded nanoentities. The Diels-Alder reaction resulted in the formation of stiffer networks with lower swelling ratios due to the formation of additional cross-linking points. The designed "click" strategy proved to be a promising candidate for the formation of fully renewable bionanocomposite hydrogels.


Temporal patterns of transient-evoked otoacoustic emissions in normal and impaired cochleae.
The spatial distribution of outer hair cells that participate in generating transient-EOE frequency-components has been investigated in man. According to several models (e.g. Wilson (1990) Hear. Res. 2, 527-532; Zwicker (1986) J. Acoust. Soc. Am. 80, 154-162; Wilson and Kemp (Eds.), Cochlear Mechanisms, Structures, Functions and Models, Plenum Press, NY), EOEs result from interferences between broadly distributed contributions, responsible for their long frequency-dependent delay. This work presents an analysis of the temporal patterns of click- and tone-burst-EOEs in human ears when contributions to EOEs are reduced by noise-induced lesions with audiometric notches centred around 4 kHz (N = 46). Although the auditory thresholds at the frequencies of the studied EOE-components were always normal, these components exhibited drastic and predictable changes compared to normal control ears (N = 40). (1) Their temporal pattern at the highest EOE frequency fmax just below the audiometric notch appeared to be determined by the cochlear state at high frequencies (6 to 8 kHz). Either it was normal and the EOE exhibited a complicated beat-structure, or it was impaired and the time envelope of the EOE was simple. In contrast, any type of time pattern could be observed in normal ears. (2) The temporal patterns of EOEs one octave below fmax always presented many beats and short delays. The proposed interpretation is that contributions to a transient-EOE component at frequency f can come from distant basal cochlear areas, i.e. more than 1 and sometimes 1.5 octaves from the place tuned to f. Therefore, the possible relationships between transient-EOEs and tuning mechanisms which presumably involve only a small number of OHC need further investigations.


Intratubular penetration of endodontic sealers depends on the fluorophore used for CLSM assessment.
Root canal filling aims at eliminating empty spaces into the root canal system using biologically compatible materials. Three-dimensional root canal obturation must prevent or minimize the reinfection caused by microorganisms' leakage. This study aimed at evaluating whether fluorophore (Rhodamine or Fluo-3) influences the CLSM images of intratubular penetration of four endodontic sealers. Eighty bovine teeth were prepared using K files up to a size #70 and irrigated with 2.5% sodium hypochlorite. All roots were divided into eight groups (n = 10) according to the sealer and fluorophore used: AH Plus/Rhodamine, AH Plus/Fluo-3, Sealer Plus/Rhodamine, Sealer Plus/Fluo-3, Sealer Plus BC/Rhodamine, Sealer Plus BC/Fluo-3, Endosequence/Rhodamine, and Endosequence/Fluo-3. All roots were filled using cold lateral compaction technique. After 7 days, the roots were transversely sectioned, and three slices, one of each canal third, were obtained. Intratubular penetration was evaluated using CLSM. Sealer Plus BC/Rhodamine and Endosequence BC/Rhodamine presented higher intratubular penetration than AH Plus/Fluo-3 and Sealer Plus/Fluo-3 (p ˂ .05). The intragroup analysis showed similar intratubular penetration, regardless of the root third, except for the apical third in AH Plus/Fluo-3 and Sealer Plus BC/Fluo-3 groups. The type of fluorophore influences the calcium silicate sealers' tubular penetration but not of epoxy resin-based ones using CLSM. Bioceramic sealers should not be used associated with Rhodamine for CLSM evaluation. RESEARCH HIGHLIGHTS: The type of fluorophore influences the calcium silicate sealers' tubular penetration but not of epoxy resin-based ones when CLSM is used for assessment. Bioceramic sealers should not be used associated with Rhodamine.


Sterility introduced by release of genetically altered males to a domestic population of Aedes aegypti at the Kenya coast.
The release of males heterozygous for one or two sex-linked translocations was effective in introducing a high level of sterility into a domestic population of Aedes aegypti at a Rabai village. The effect of the releases continued for several weeks after the release period.


Association of sleep disturbance and freezing of gait in Parkinson disease: prevention/delay implications.
Freezing of gait (FOG) severely impairs life quality of Parkinson disease (PD) patients. The relationship between sleep disturbance and FOG in PD remains unclear, so in this study, we aimed to investigate that relationship. First, we assessed clinical characteristics of freezers and nonfreezers among PD patients. Next, we assessed clinical characteristics of PD patients with different PDSS1 scores (score on first item of Parkinson's Disease Sleep Scale). Finally, we prospectively followed a cohort of nonfreezers from a baseline clinical visit and to a maximum of 18 months and performed a Cox regression analysis to further investigate the relationship between PDSS1 score and FOG in PD. A total of 163 participants with PD were included in the baseline analysis. The freezers had significantly worse sleep compared with the nonfreezers. The proportion of freezers in the patients with low PDSS1 score (PDSS1 < 6) was significantly higher than that in the patients with high PDSS1 score (PDSS1 ≥ 6). A total of 52 nonfreezers were prospectively followed. During a maximum 18-month follow-up, FOG incidence (73%) in the PDSS1 < 6 group was significantly higher than that (24%) in the PDSS1 ≥ 6 group (P = .008). Low PDSS1 score (hazard ratio = 4.23, 95% CI 1.64-10.92, P = .003) and high levodopa equivalent daily dose (hazard ratio = 4.18, 95% CI 1.62-10.75, P = .003) were significantly associated with an increased hazard of FOG. Our study indicated that low PDSS1 score may be a risk indicator for the development of FOG and provided important insights into potential targets for the prevention/delay of FOG in PD.